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Sökning: WFRF:(Lance M)

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5.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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  • Fresard, Laure, et al. (författare)
  • Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
  • 2019
  • Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
  • Tidskriftsartikel (refereegranskat)abstract
    • It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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  • Sumaila, U. Rashid, et al. (författare)
  • WTO must ban harmful fisheries subsidies
  • 2021
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Clark, Andrew G., et al. (författare)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Tidskriftsartikel (refereegranskat)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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10.
  • Axfors, Cathrine, et al. (författare)
  • Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
  • 2021
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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  • Nowak-Sliwinska, Patrycja, et al. (författare)
  • Consensus guidelines for the use and interpretation of angiogenesis assays
  • 2018
  • Ingår i: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 21:3, s. 425-532
  • Forskningsöversikt (refereegranskat)abstract
    • The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
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13.
  • Morin, Phillip A., et al. (författare)
  • Geographic and temporal dynamics of a global radiation and diversification in the killer whale
  • 2015
  • Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 24:15, s. 3964-3979
  • Tidskriftsartikel (refereegranskat)abstract
    • Global climate change during the Late Pleistocene periodically encroached and then released habitat during the glacial cycles, causing range expansions and contractions in some species. These dynamics have played a major role in geographic radiations, diversification and speciation. We investigate these dynamics in the most widely distributed of marine mammals, the killer whale (Orcinus orca), using a global data set of over 450 samples. This marine top predator inhabits coastal and pelagic ecosystems ranging from the ice edge to the tropics, often exhibiting ecological, behavioural and morphological variation suggestive of local adaptation accompanied by reproductive isolation. Results suggest a rapid global radiation occurred over the last 350000years. Based on habitat models, we estimated there was only a 15% global contraction of core suitable habitat during the last glacial maximum, and the resources appeared to sustain a constant global effective female population size throughout the Late Pleistocene. Reconstruction of the ancestral phylogeography highlighted the high mobility of this species, identifying 22 strongly supported long-range dispersal events including interoceanic and interhemispheric movement. Despite this propensity for geographic dispersal, the increased sampling of this study uncovered very few potential examples of ancestral dispersal among ecotypes. Concordance of nuclear and mitochondrial data further confirms genetic cohesiveness, with little or no current gene flow among sympatric ecotypes. Taken as a whole, our data suggest that the glacial cycles influenced local populations in different ways, with no clear global pattern, but with secondary contact among lineages following long-range dispersal as a potential mechanism driving ecological diversification.
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  • Vogler, Amy J, et al. (författare)
  • Phylogeography of Francisella tularensis : global expansion of a highly fit clone
  • 2009
  • Ingår i: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 191:8, s. 2474-2484
  • Tidskriftsartikel (refereegranskat)abstract
    • Francisella tularensis contains several highly pathogenic subspecies, including Francisella tularensis subsp. holarctica, whose distribution is circumpolar in the northern hemisphere. The phylogeography of these subspecies and their subclades was examined using whole-genome single nucleotide polymorphism (SNP) analysis, high-density microarray SNP genotyping, and real-time-PCR-based canonical SNP (canSNP) assays. Almost 30,000 SNPs were identified among 13 whole genomes for phylogenetic analysis. We selected 1,655 SNPs to genotype 95 isolates on a high-density microarray platform. Finally, 23 clade- and subclade-specific canSNPs were identified and used to genotype 496 isolates to establish global geographic genetic patterns. We confirm previous findings concerning the four subspecies and two Francisella tularensis subsp. tularensis subpopulations and identify additional structure within these groups. We identify 11 subclades within F. tularensis subsp. holarctica, including a new, genetically distinct subclade that appears intermediate between Japanese F. tularensis subsp. holarctica isolates and the common F. tularensis subsp. holarctica isolates associated with the radiation event (the B radiation) wherein this subspecies spread throughout the northern hemisphere. Phylogenetic analyses suggest a North American origin for this B-radiation clade and multiple dispersal events between North America and Eurasia. These findings indicate a complex transmission history for F. tularensis subsp. holarctica.
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  • Lindblad-Toh, Kerstin, et al. (författare)
  • Genome sequence, comparative analysis and haplotype structure of the domestic dog.
  • 2005
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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  • Mikkelsen, Tarjei S, et al. (författare)
  • Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7141, s. 167-177
  • Tidskriftsartikel (refereegranskat)abstract
    • We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
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  • Catella, Stephanie, et al. (författare)
  • Self-guided digital acceptance and commitment therapy for fibromyalgia management : results of a randomized, active-controlled, phase II pilot clinical trial
  • 2024
  • Ingår i: Journal of behavioral medicine. - : Springer. - 0160-7715 .- 1573-3521. ; 47:1, s. 27-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Although empirically validated for fibromyalgia (FM), cognitive and behavioral therapies, including Acceptance and Commitment Therapy (ACT), are inaccessible to many patients. A self-guided, smartphone-based ACT program would significantly improve accessibility. The SMART-FM study assessed the feasibility of conducting a predominantly virtual clinical trial in an FM population in addition to evaluating preliminary evidence for the safety and efficacy of a digital ACT program for FM (FM-ACT). Sixty-seven patients with FM were randomized to 12 weeks of FM-ACT (n = 39) or digital symptom tracking (FM-ST; n = 28). The study population was 98.5% female, with an average age of 53 years and an average baseline FM symptom severity score of 8 out of 11. Endpoints included the Fibromyalgia Impact Questionnaire-Revised (FIQ-R) and the Patient Global Impression of Change (PGIC). The between-arm effect size for the change from baseline to Week 12 in FIQ-R total scores was d = 0.44 (least-squares mean difference, − 5.7; SE, 3.16; 95% CI, − 11.9 to 0.6; P = .074). At Week 12, 73.0% of FM-ACT participants reported improvement on the PGIC versus 22.2% of FM-ST participants (P < .001). FM-ACT demonstrated improved outcomes compared to FM-ST, with high engagement and low attrition in both arms. Retrospectively registered at ClinicalTrials.gov (NCT05005351) on August 13, 2021.
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  • Gendreau, R. Michael, et al. (författare)
  • Self-guided digital behavioural therapy versus active control for fibromyalgia (PROSPER-FM) : a phase 3, multicentre, randomised controlled trial
  • 2024
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 404:10450, s. 364-374
  • Tidskriftsartikel (refereegranskat)abstract
    • Background International guidelines have recommended cognitive behavioural therapy, including acceptance and commitment therapy (ACT), as it offers validated benefits for managing fibromyalgia; however, it is inaccessible to most patients. We aimed to evaluate the effect of a 12-week, self-guided, smartphone-delivered digital ACT programme on fibromyalgia management. Methods In the PROSPER-FM randomised clinical trial conducted at 25 US community sites, adult participants aged 22-75 years with fibromyalgia were recruited and randomly assigned (1:1) to the digital ACT group or an active control group that offered daily symptom tracking and monitoring and access to health-related and fibromyalgiarelated educational materials. Randomisation was done with a web-based system in permuted blocks of four at the site level. We used a blind-to-hypothesis approach in which participants were informed they would be randomly assigned to one of two potentially effective therapies under evaluation. Research staff were not masked to group allocation, with the exception of a masked statistics group while preparing statistical programming for the interim analysis. The primary endpoint was patient global impression of change (PGIC) response rate at week 12. Analyses were by intention to treat. The trial was registered with ClinicalTrials.gov, NCT05243511 (now fully closed). Findings Between Feb 8, 2022, and Feb 2, 2023, 590 individuals were screened, of whom 275 (257 women and 18 men) were randomly assigned to the digital ACT group (n=140) and the active control group (n=135). At 12 weeks, 99 (71%) of 140 ACT participants reported improvement on PGIC versus 30 (22%) of 135 active control participants, corresponding to a difference in proportions of 484% (95% CI 379-589; p<00001). No device-related safety events were reported. Interpretation Digital ACT was safe and efficacious compared with digital symptom tracking in managing fibromyalgia in adult patients. Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.
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  • Kasivisvanathan, Veeru, et al. (författare)
  • MRI-targeted or standard biopsy for prostate-cancer diagnosis
  • 2018
  • Ingår i: New England Journal of Medicine. - 0028-4793. ; 378:19, s. 1767-1777
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. METHODS: In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. RESULTS: A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P = 0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). CONCLUSIONS: The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027.)
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20.
  • Kilbaugh, Todd J, et al. (författare)
  • Persistently Altered Brain Mitochondrial Bioenergetics After Apparently Successful Resuscitation From Cardiac Arrest.
  • 2015
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 4, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Although advances in cardiopulmonary resuscitation have improved survival from cardiac arrest (CA), neurologic injury persists and impaired mitochondrial bioenergetics may be critical for targeted neuroresuscitation. The authors sought to determine if excellent cardiopulmonary resuscitation and postresuscitation care and good traditional survival rates result in persistently disordered cerebral mitochondrial bioenergetics in a porcine pediatric model of asphyxia-associated ventricular fibrillation CA.
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  • Moure, Vivian R., et al. (författare)
  • The ammonium transporter AmtB and the PII signal transduction protein GlnZ are required to inhibit DraG in Azospirillum brasilense
  • 2019
  • Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 286:6, s. 1214-1229
  • Tidskriftsartikel (refereegranskat)abstract
    • The ammonium-dependent posttranslational regulation of nitrogenase activity in Azospirillum brasilense requires dinitrogenase reductase ADPribosyl transferase (DraT) and dinitrogenase reductase ADP-glycohydrolase (DraG). These enzymes are reciprocally regulated by interaction with the PII proteins, GlnB and GlnZ. In this study, purified ADP-ribosylated Fe-protein was used as substrate to study the mechanism involved in the regulation of A. brasilense DraG in vitro. The data show that DraG is partially inhibited by GlnZ and that DraG inhibition is further enhanced by the simultaneous presence of GlnZ and AmtB. These results are the first to demonstrate experimentally that DraG inactivation requires the formation of a ternary DraG-GlnZ-AmtB complex in vitro. Previous structural data have revealed that when the DraG-GlnZ complex associates with AmtB, the flexible T-loops of the trimeric GlnZ bind to AmtB and become rigid; these molecular events stabilize the DraG-GlnZ complex, resulting in DraG inactivation. To determine whether restraining the flexibility of the GlnZ T-loops is a limiting factor in DraG inhibition, we used a GlnZ variant that carries a partial deletion of the T-loop (GlnZD42-54). However, although the GlnZD42-54 variant was more effective in inhibiting DraG in vitro, it bound to DraG with a slightly lower affinity than does wild-type GlnZ and was not competent to completely inhibit DraG activity either in vitro or in vivo. We, therefore, conclude that the formation of a ternary complex between DraG-GlnZ-AmtB is necessary for the inactivation of DraG.
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23.
  • Sikkema, Lisa, et al. (författare)
  • An integrated cell atlas of the lung in health and disease
  • 2023
  • Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 29:6, s. 1563-1577
  • Tidskriftsartikel (refereegranskat)abstract
    • Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
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24.
  • Struwe, Weston B, et al. (författare)
  • The minimum information required for a glycomics experiment (MIRAGE) project: sample preparation guidelines for reliable reporting of glycomics datasets.
  • 2016
  • Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 26:9, s. 907-910
  • Tidskriftsartikel (refereegranskat)abstract
    • Theminimum information required for a glycomics experiment (MIRAGE) project was established in 2011 to provide guidelines to aid in data reporting from all types of experiments in glycomics research including mass spectrometry (MS), liquid chromatography, glycan arrays, data handling and sample preparation. MIRAGE is a concerted effort of the wider glycomics community that considers the adaptation of reporting guidelines as an important step towards critical evaluation and dissemination of datasets as well as broadening of experimental techniques worldwide. The MIRAGE Commission published reporting guidelines for MS data and here we outline guidelines for sample preparation. The sample preparation guidelines include all aspects of sample generation, purification and modification from biological and/or synthetic carbohydrate material. The application of MIRAGE sample preparation guidelines will lead to improved recording of experimental protocols and reporting of understandable and reproducible glycomics datasets.
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25.
  • Timmers, Inge, et al. (författare)
  • Parent psychological flexibility in the context of pediatric pain : Brief assessment and associations with parent behaviour and child functioning.
  • 2019
  • Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 23:7, s. 1340-1350
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The parent's role in the context of pediatric chronic pain is essential. There is growing evidence that parent psychological flexibility positively impacts child functioning. To assess parents' abilities to respond with psychological flexibility to their child's pain, the Parent Psychological Flexibility Questionnaire (PPFQ) was developed. Here, we aim to validate the 10-item version of the questionnaire in an English-speaking population and to evaluate associations with parent behaviour, child pain acceptance and functioning.METHODS: Five hundred and seventy-eight parent-child dyads presenting at a pediatric pain clinic were included (92% mothers, average child age 15.2 ± 1.6 years). The PPFQ was completed by the parent. Parent and child also completed other standardized questionnaires. In addition to confirmatory factor analysis and assessments of reliability and validity of the PPFQ-10, a mediation analysis was performed to examine the direct and indirect effects of parent psychological flexibility on child functioning.RESULTS: Confirmatory factor analysis supported the three-factor model with subscales for Values-Based Action, Pain Willingness and Emotional Acceptance, and the PPFQ-10 demonstrated strong psychometric properties. After controlling for child pain, parent psychological flexibility indirectly affected child functioning through its association with both parent behaviour (i.e., protectiveness) and child pain acceptance.CONCLUSIONS: Our findings provide further support for use of the PPFQ-10 and the importance of assessing and addressing parent psychological flexibility in the context of child chronic pain. Our data show that parent psychological flexibility has an important adaptive role and can impact child functioning through two different routes, both of which can be actively targeted in treatment.SIGNIFICANCE: Our findings demonstrate that the PPFQ-10 is an efficient measure of parent psychological flexibility, demonstrating strong psychometric properties. Furthermore, our analyses showed that parent psychological flexibility indirectly affects child functioning through associations with both adaptive parent behaviour and child functioning. Taken together, this study furthers the understanding of how parent psychological flexibility operates and affects children with chronic pain, and may inform and optimize treatments aimed at improving functioning by addressing child and parent coping.
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26.
  • Wik, Martin, et al. (författare)
  • Sediment Characteristics and Methane Ebullition in Three Subarctic Lakes
  • 2018
  • Ingår i: Journal of Geophysical Research - Biogeosciences. - 2169-8953 .- 2169-8961. ; 123:8, s. 2399-2411
  • Tidskriftsartikel (refereegranskat)abstract
    • Ebullition (bubbling) from climate-sensitive northern lakes remains an unconstrained source of atmospheric methane (CH4). Although the focus of many recent studies, ebullition is rarely linked to the physical characteristics of lakes. In this study we analyze the sediments of subarctic postglacial lakes and investigate how sediment properties relate to the large spatial variation in CH4 bubble flux, quantified over multiple years using bubble traps. The results show that the sediments from our lakes are rich in total organic carbon, containing 37 kg/m(3) on average. This number is roughly 40% higher than the average for yedoma deposits, which have been identified as high CH4 emitters. However, the quantity of total organic carbon is not a useful indicator of high emissions from the study lakes. Neither is the amount of CH4 in the sediment a reliable measure of ebullition potential. Instead, our data point to coarse detritus, partly from buried submerged aquatic vegetation and redeposited peat as spatial controls on fluxes, often in combination with previously established effects of incoming solar radiation and water depth. The results once again highlight the climate sensitivity of northern lakes, indicating that biological responses to warmer waters and increased energy input and heating of organic sediments during longer ice-free seasons can substantially alter future CH4 emissions.
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27.
  • Anderson, Madeleine, et al. (författare)
  • An investigation of the associations between stigma, self-compassion, and pain outcomes during treatment based on Acceptance and Commitment Therapy for chronic pain
  • 2024
  • Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Stigma adversely affects people with chronic pain. The qualities within self-compassion may be particularly useful for buffering the impact of stigma on people with pain. In the context of an Acceptance and Commitment Therapy-based (ACT) treatment for chronic pain, this study investigated the association between changes in stigma and self-compassion and pain outcomes, and the potential moderating role of self-compassion on the association between stigma and pain outcomes.Materials and methods: Five-hundred and nineteen patients completed standardized self-report questionnaires of stigma, self-compassion, psychological flexibility, pain intensity and interference, work and social adjustment, and depression symptoms at the start of an interdisciplinary ACT-based treatment for chronic pain. The same measures were completed at post-treatment (n = 431).Results: The results indicated that key pain outcomes and self-compassion significantly improved during treatment, but stigma did not. Changes in stigma and self-compassion were significantly negatively correlated and changes in these variables were associated with improvements in treatment outcomes. There were significant main effects of stigma and self-compassion for many of the pre- and post-treatment regression models when psychological flexibility was not controlled for, but self-compassion did not moderate the association between stigma and pain outcomes. Stigma remained significant when psychological flexibility variables were controlled for, while self-compassion did not.Discussion: The findings add to our conceptual understanding of the inter-relationships between stigma, self-compassion, and psychological flexibility and can contribute to treatment advancements to optimally target these variables.
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28.
  • Angeler, David, et al. (författare)
  • Management applications of discontinuity theory
  • 2016
  • Ingår i: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 53:3, s. 688-698
  • Forskningsöversikt (refereegranskat)abstract
    • 1. Human impacts on the environment are multifaceted and can occur across distinct spatiotemporal scales. Ecological responses to environmental change are therefore difficult to predict, and entail large degrees of uncertainty. Such uncertainty requires robust tools for management to sustain ecosystem goods and services and maintain resilient ecosystems. 2. We propose an approach based on discontinuity theory that accounts for patterns and processes at distinct spatial and temporal scales, an inherent property of ecological systems. Discontinuity theory has not been applied in natural resource management and could therefore improve ecosystem management because it explicitly accounts for ecological complexity. 3. Synthesis and applications. We highlight the application of discontinuity approaches for meeting management goals. Specifically, discontinuity approaches have significant potential to measure and thus understand the resilience of ecosystems, to objectively identify critical scales of space and time in ecological systems at which human impact might be most severe, to provide warning indicators of regime change, to help predict and understand biological invasions and extinctions and to focus monitoring efforts. Discontinuity theory can complement current approaches, providing a broader paradigm for ecological management and conservation.
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29.
  • Arance, Ana, et al. (författare)
  • Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination.
  • 2023
  • Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 41:1, s. 75-85
  • Tidskriftsartikel (refereegranskat)abstract
    • Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136).Eligible patients with unresectable stage III-IV melanoma with confirmed progressive disease (PD) within 12 weeks of the last dose of a PD-1/L1 inhibitor given alone or with other therapies, including cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4) inhibitors, received lenvatinib 20 mg orally once daily plus ≤ 35 doses of pembrolizumab 200 mg intravenously once every 3 weeks until PD or unacceptable toxicity. The primary end point was objective response rate (ORR) per RECIST, version 1.1, by independent central review.A total of 103 patients were enrolled and treated. The median study follow-up was 15.3 months. ORR in the total population was 21.4% (95% CI, 13.9 to 30.5), with three (2.9%) complete responses and 19 (18.4%) partial responses. The median duration of response was 8.3 months (range, 3.2-15.9+). ORR was 33.3% in the 30 patients with PD on prior anti-PD-1 plus anti-CTLA-4 therapy. The median progression-free survival and overall survival in the total population were 4.2 months (95% CI, 3.8 to 7.1) and 14.0 months (95% CI, 10.8 to not reached), respectively. Grade 3-5 treatment-related adverse events occurred in 47 (45.6%) patients, most commonly hypertension (21.4%); one patient died from a treatment-related event (decreased platelet count).Lenvatinib plus pembrolizumab provides clinically meaningful, durable responses in patients with advanced melanoma with confirmed PD on prior PD-1/L1 inhibitor-based therapy, including those with PD on anti-PD-1 plus anti-CTLA-4 therapy. The safety profile was as expected. These data support lenvatinib plus pembrolizumab as a potential regimen for this population of high unmet need.
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30.
  • Bartels, Sara Laureen, et al. (författare)
  • Using Personas in the development of eHealth interventions for chronic pain : A scoping review and narrative synthesis
  • 2023
  • Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 32
  • Forskningsöversikt (refereegranskat)abstract
    • Objectives: Behavioral eHealth interventions can enhance self-management and improve well-being in people with chronic pain. The development of these interventions calls for a user-centered approach to ensure that patient needs are appreciated. However, it may be challenging to involve patients; particularly during the early stages of the process. Fictional user profiles, known as Personas, can represent needs and guide designing eHealth interventions. This article provides a comprehensive overview of the use of Personas in the development of behavioral eHealth interventions for people with chronic pain with the aim to identify benefits and challenges. Methods: Bibliographic databases (Medline, Web of Science Core Collection, PsycInfo, CINAHL) and registries (PubMed Central, medaRxiv) were systematically searched. In a double-reviewing process, n = 6830 hits and n = 351 full-texts were screened and read. Ten peer-reviewed studies published between 2017 and 2022 were included in the narrative synthesis. Findings: Ten studies reported using "Pain Personas" in the development of eHealth interventions for such purposes as to gain a shared understanding of the user and to discuss solutions in team meetings, or for patients to identify with (if Personas are included in the intervention). Personas were based on qualitative and/or quantitative data. However, the procedure for creating Personas was only described in half of the included studies (n = 5). These five studies provided descriptive details of the Personas (i.e., picture, name, narrative of their pain behavior, technological skills, and motivation). Conclusions: Although Personas have been used by pain researchers in recent projects and were highlighted as an important ingredient in the development process, available design guidelines for the creation and use of Personas are not followed or communicated transparently. Benefits and challenges when using Personas in the development of eHealth interventions for people with chronic pain are discussed to support future eHealth efforts and to improve the quality of eHealth innovation in the field of pain.
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31.
  • Björkstrand, Frida Köhler, et al. (författare)
  • Access to psychological treatment for chronic cancer-related pain in Sweden
  • 2024
  • Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Cancer-related pain (CRP) is among the most frequent collateral effects of cancer, with chronic CRP, lasting at least 3 months, affecting >40% of cancer survivors. Evidence-based treatments, including pain-focused cognitive behavioral therapy (CBT), are available, but it appears that cancer patients/survivors are often poorly informed about CRP or the potential benefits of CBT for such pain. This study examined current experience of Swedish cancer patients/survivors in relation to CRP. Methods Participants (N = 276; 83% female; mean age = 55.5 years, SD = 11.9) were recruited to an online survey via cancer websites in Sweden, and they provided information about their history of chronic CRP and whether they received information about or treatment for CRP from a healthcare professional. Results Participants had a history of breast (36%), gynecological (12%), lung (10%), colon (8%), and other forms of cancer (36%). A majority (74%) reported a history of chronic CRP and being prescribed analgesic medications (70%). Less than half (47%) received information from their healthcare provider about the risk of CRP and only 13% with chronic CRP received psychological treatment, and of these, only 33% received CBT. Among those receiving psychological treatment for chronic CRP, satisfaction rates were moderate, reported as an average of 6 on a 0-10 scale (standard deviation 2.6). Conclusions Greater efforts are needed to raise awareness among cancer patients/survivors and healthcare providers about the risk of CRP and evidence-based interventions, including CBT, the first-line intervention for chronic pain. These efforts will need to be matched with increases in treatment capacity, particularly pain-focused CBT.
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32.
  • Bothelius, Kristoffer, 1973-, et al. (författare)
  • Measuring Acceptance of Sleep Difficulties : The Development of the Sleep Problem Acceptance Questionnaire
  • 2015
  • Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 38:11, s. 1815-1822
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Objectives: Acceptance may be an important therapeutic process in sleep medicine, but valid psychometric instruments measuring acceptance related to sleep difficulties are lacking. The purpose of this study was to develop a measure of acceptance in insomnia, and to examine its factor structure as well as construct validity. Design: In a cross-sectional design, a principal component analysis for item reduction was conducted on a first sample (A) and a confirmatory factor analysis on a second sample (B). Construct validity was tested on a combined sample (C). Setting: Questionnaire items were derived from a measure of acceptance in chronic pain, and data were gathered through screening or available from pretreatment assessments in four insomnia treatment trials, administered online, via bibliotherapy and in primary care. Participants: Adults with insomnia: 372 in sample A and 215 in sample B. Sample C (n = 820) included sample A and B with another 233 participants added. Measures: Construct validity was assessed through relations with established acceptance and sleep scales. Results: The principal component analysis presented a two-factor solution with eight items, explaining 65.9% of the total variance. The confirmatory factor analysis supported the solution. Acceptance of sleep problems was more closely related to subjective symptoms and consequences of insomnia than to diary description of sleep, or to acceptance of general private events. Conclusions: The Sleep Problem Acceptance Questionnaire (SPAQ), containing the subscales "Activity Engagement" and "Willingness", is a valid tool to assess acceptance of insomnia.
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33.
  • Casey, Maire-Brid, et al. (författare)
  • Exercise combined with Acceptance and Commitment Therapy compared with a standalone supervised exercise programme for adults with chronic pain : a randomised controlled trial
  • 2022
  • Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 163:6, s. 1158-1171
  • Tidskriftsartikel (refereegranskat)abstract
    • A prospective, 2-armed, parallel group randomised controlled trial (RCT) was conducted to compare the effectiveness of Acceptance and Commitment Therapy (ACT) combined with a supervised exercise programme with a supervised exercise programme alone for adults with chronic pain. One hundred seventy-five participants were individually randomised to receive either the combined Exercise and ACT (ExACT) intervention or supervised exercise alone. Those allocated to the ExACT group attended 8 weekly sessions with a psychologist based on the ACT approach, in addition to supervised exercise classes led by a physiotherapist. The control group attended weekly supervised exercise classes but did not take part in an ACT programme. Both groups were followed up postintervention and again after 12 weeks. The primary outcome was pain interference at 12-week follow-up. Estimates of treatment effects at follow-up were based on intention-to-treat analyses, implemented using a linear mixed-effects model. The findings of this RCT showed no difference in the effectiveness of ExACT, compared with a supervised exercise programme alone for the primary outcome pain interference at 12-week follow-up (mean difference -0.18, 95% confidence interval -0.84 to 0.48, P = 0.59, d = 0.11). ExACT group participants reported superior outcomes for pain self-efficacy, pain catastrophising, and committed action, compared with the control group, but there were no differences between the groups for other secondary outcomes or treatment process measures. Higher levels of treatment satisfaction and global impression of change were reported by ExACT group participants. Exercise combined with Acceptance and Commitment Therapy was not superior to a standalone supervised exercise programme for reducing pain interference in adults with chronic pain.
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34.
  • Clason van de Leur, Jakob, et al. (författare)
  • Mediators during a multimodal intervention for stress-induced exhaustion disorder
  • 2024
  • Ingår i: Cognitive Behaviour Therapy. - : Routledge. - 1650-6073 .- 1651-2316. ; 53:3, s. 235-253
  • Tidskriftsartikel (refereegranskat)abstract
    • Our understanding of the underlying psychological processes of development, maintenance, and treatments for stress-induced exhaustion disorder (ED) remains limited. Therefore, the current study aimed to explore whether sleep concerns, pathological worry, perfectionistic concerns, and psychological flexibility mediate change in exhaustion symptoms during a Multimodal intervention for ED based on Cognitive behavioral therapy principles. Participants (N = 913) were assessed at three time points, and mediation was explored using a two-criteria analytical model with linear mixed-effects models (criterion one) and random intercepts cross-lagged panel modeling (criterion 2). Criterion one for mediation was successfully met, as the findings indicated significant associations between time in treatment, with all suggested mediators, and exhaustion symptoms (significant ab-products). However, criterion two was not satisfied as changes in the mediators did not precede changes in exhaustion symptoms. Therefore, mediation could not be established. Instead, changes in the suggested mediators appeared to result from changes in exhaustion symptoms. Consequently, sleep concerns, pathological worry, perfectionistic concerns, and psychological flexibility appear to improve in conjunction with exhaustion symptoms during treatment, where improvement in exhaustion is indicated as the main driving factor, based on this exploratory analysis. The implications of these findings are contextualized within a broader framework of process-based therapy.
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35.
  • Clason van de Leur, Jakob, et al. (författare)
  • Psychological Treatment of Exhaustion Due to Persistent Non-Traumatic Stress : A Scoping Review
  • 2024
  • Ingår i: International Journal of Behavioral Medicine. - : Springer. - 1070-5503 .- 1532-7558. ; 31:2, s. 175-191
  • Forskningsöversikt (refereegranskat)abstract
    • BackgroundExhaustion due to persistent non-traumatic stress (ENTS) is a significant health problem with substantial personal, social, and economic impact. While there are increasing studies of ENTS, there is no international agreement on how it should be diagnosed and treated. This scoping review aimed to map definitions, diagnoses, treatments, outcome measures, and outcomes in psychological treatment studies of ENTS. A further aim was to assess the quality of the treatments and map what change processes are described within ENTS interventions.MethodsA PRISMA-guided scoping review of psychological treatment studies delivered in a clinical setting for ENTS was conducted using the databases of PubMed, PsycINFO, and CINAHL.ResultsOf the 60 studies included, the majority (87%) stemmed from Europe. The most recurrent term for ENTS was burnout, and the diagnosis most often utilized was exhaustion disorder. Several treatments were reported, the most frequent being cognitive behavioral therapy (CBT) (68%). Statistically significant outcomes relevant to ENTS were reported in 65% (n = 39) of the studies, with effect sizes between 0.13 and 1.80. In addition, 28% of the treatments were rated as high quality. The most frequent change processes described were dysfunctional sleep, avoidance, behavioral activation, irrational thoughts and beliefs, worry, perceived competence/positive management, psychological flexibility, and recuperation.ConclusionsWhile several treatments based on CBT show promising results for ENTS, there do not seem to be any uniformly established methods, theoretical models, or change processes. Instead of adopting a monocausal, syndromal, and potentially bio-reductionist perspective on ENTS, a process-based approach to treatment is encouraged.
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36.
  • Coates, Brad S., et al. (författare)
  • A draft Diabrotica virgifera virgifera genome : insights into control and host plant adaption by a major maize pest insect
  • 2023
  • Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Adaptations by arthropod pests to host plant defenses of crops determine their impacts on agricultural production. The larval host range of western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), is restricted to maize and a few grasses. Resistance of D. v. virgifera to crop rotation practices and multiple insecticides contributes to its status as the most damaging pest of cultivated maize in North America and Europe. The extent to which adaptations by this pest contributes to host plant specialization remains unknown. Results: A 2.42 Gb draft D. v. virgifera genome, Dvir_v2.0, was assembled from short shotgun reads and scaffolded using long-insert mate-pair, transcriptome and linked read data. K-mer analysis predicted a repeat content of ≥ 61.5%. Ortholog assignments for Dvir_2.0 RefSeq models predict a greater number of species-specific gene duplications, including expansions in ATP binding cassette transporter and chemosensory gene families, than in other Coleoptera. A majority of annotated D. v. virgifera cytochrome P450s belong to CYP4, 6, and 9 clades. A total of 5,404 transcripts were differentially-expressed between D. v. virgifera larvae fed maize roots compared to alternative host (Miscanthus), a marginal host (Panicum virgatum), a poor host (Sorghum bicolor) and starvation treatments; Among differentially-expressed transcripts, 1,908 were shared across treatments and the least number were between Miscanthus compared to maize. Differentially-expressed transcripts were enriched for putative spliceosome, proteosome, and intracellular transport functions. General stress pathway functions were unique and enriched among up-regulated transcripts in marginal host, poor host, and starvation responses compared to responses on primary (maize) and alternate hosts. Conclusions: Manual annotation of D. v. virgifera Dvir_2.0 RefSeq models predicted expansion of paralogs with gene families putatively involved in insecticide resistance and chemosensory perception. Our study also suggests that adaptations of D. v. virgifera larvae to feeding on an alternate host plant invoke fewer transcriptional changes compared to marginal or poor hosts. The shared up-regulation of stress response pathways between marginal host and poor host, and starvation treatments may reflect nutrient deprivation. This study provides insight into transcriptomic responses of larval feeding on different host plants and resources for genomic research on this economically significant pest of maize.
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37.
  • Contreras, Milena, et al. (författare)
  • Therapists' perceptions and acceptability of providing internet-delivered guided self-help acceptance and commitment therapy (ACT) for family carers of people with dementia (iACT4CARERS) : a qualitative study
  • 2021
  • Ingår i: The Cognitive Behaviour Therapist. - : Cambridge University Press. - 1754-470X. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to explore therapists' perceptions and acceptability of providing internet-delivered, therapist-guided, self-help acceptance and commitment therapy (ACT) for family carers of people with dementia (iACT4CARERS). To achieve this, a qualitative approach with semi-structured interviews was employed with eight novice therapists recruited from primary and secondary care services taking part in a feasibility study of iACT4CARERS. The interviews were audio-recorded, transcribed, and analysed using thematic analysis. Four over-arching themes were identified: (1) positive attitudes towards the intervention, (2) therapists' workload, (3) therapists' confidence to perform their role, and (4) connecting with family carers in a virtual context. Theme 1 included seeing their involvement as an opportunity for personal growth and perceiving benefits to the family carers, which contributed to greater acceptability. Theme 2 reflected that while workload and the user-friendliness of the online platform were highly acceptable among the therapists, there were also time-consuming cases that increased therapists' burden. Theme 3 revealed that practical resources provided during the training, continued supervision, and opportunities to learn from other therapists, increased therapist confidence and facilitated greater acceptability. Finally, Theme 4 highlighted that improving the connection between therapists and carers was critical in a virtual context and strategies to improve the therapist-carer relationship were recommended. The implementation of iACT4CARERS was largely acceptable for the therapists involved in the trial. Ways to strengthen the therapeutic relationship in the virtual context and practical strategies to deal with common problems may enhance therapist experience and delivery in a full-scale effectiveness trial.
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38.
  • Cruz, Rodrigo G.B., et al. (författare)
  • Human epidermal growth factor receptor-3 expression is regulated at transcriptional level in breast cancer settings by junctional adhesion molecule-a via a pathway involving beta-catenin and foxa1
  • 2021
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The success of breast cancer therapies targeting the human epidermal growth factor receptor-2 (HER2) is limited by the development of drug resistance by mechanisms including upregulation of HER3. Having reported that HER2 expression and resistance to HER2-targeted therapies can be regulated by Junctional Adhesion Molecule-A (JAM-A), this study investigated if JAM-A regulates HER3 expression. Expressional alteration of JAM-A in breast cancer cells was used to test expressional effects on HER3 and its effectors, alongside associated functional behaviors, in vitro and semi-in vivo. HER3 transcription factors were identified and tested for regulation by JAM-A. Finally a patient tissue microarray was used to interrogate connections between putative pathway components connecting JAM-A and HER3. This study reveals for the first time that HER3 and its effectors are regulated at gene/protein expression level by JAM-A in breast cancer cell lines; with functional consequences in in vitro and semi-in vivo models. In bioinformatic, cellular and patient tissue models, this was associated with regulation of the HER3 transcription factor FOXA1 by JAM-A via a pathway involving β-catenin. Our data suggest a novel model whereby JAM-A expression regulates β-catenin localization, in turn regulating FOXA1 expression, which could drive HER3 gene transcription. JAM-A merits investigation as a novel target to prevent upregulation of HER3 during the development of resistance to HER2-targeted therapies, or to reduce HER3-dependent tumorigenic signaling.
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39.
  •  
40.
  • De Hert, S, et al. (författare)
  • Aprotinin: is it time to reconsider?
  • 2015
  • Ingår i: European journal of anaesthesiology. - 1365-2346. ; 32:9, s. 591-595
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
41.
  • Feliu-Soler, Albert, et al. (författare)
  • Economic Impact of Third-Wave Cognitive Behavioral Therapies : A Systematic Review and Quality Assessment of Economic Evaluations in Randomized Controlled Trials
  • 2018
  • Ingår i: Behavior Therapy. - : Elsevier BV. - 0005-7894 .- 1878-1888. ; 49:1, s. 124-147
  • Tidskriftsartikel (refereegranskat)abstract
    • The term third-wave cognitive behavioral therapy (CBT) encompasses new forms of CBT that both extend and innovate within CBT. Most third-wave therapies have been subject to randomized controlled trials (RCTs) focused on clinical effectiveness; however, the number and quality of economic evaluations in these RCTs has been unknown and may be few. Evidence about efficiency of these therapies may help support decisions on efficient allocation of resources in health policies. The main aim of this study was to systematically review the economic impact of third-wave therapies in the treatment of patients with physical or mental conditions. We conducted a systematic literature search in PubMed, PsycINFO, EMBASE, and CINALH to identify economic evaluations of third-wave therapies. Quality and Risk of Bias (RoB) assessment of economic evaluations was also made using the Drummond 35-item checklist and the Cochrane Collaboration's tool for assessing risk of bias, respectively. Eleven RCTs were included in this systematic review. Mindfulness-Based Cognitive Therapy (MBCT), Mindfulness-Based Stress Reduction (MBSR), Acceptance and Commitment Therapy (ACT), Dialectical Behavior Therapy (DBT), and extended Behaviour Activation (eBA) showed acceptable cost-effectiveness and cost-utility ratios. No study employed a time horizon of more than 3 years. Quality and RoB assessments highlight some limitations that temper the findings. There is some evidence that MBCT, MBSR, ACT, DBT, and eBA are efficient from a societal or a third-party payer perspective. No economic analysis was found for many third-wave therapies. Therefore, more economic evaluations with high methodological quality are needed.
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42.
  • Ferguson, Michael A, et al. (författare)
  • Increased platelet mitochondrial respiration after cardiac arrest and resuscitation as a potential peripheral biosignature of cerebral bioenergetic dysfunction
  • 2016
  • Ingår i: Journal of Bioenergetics and Biomembranes. - : Springer Science and Business Media LLC. - 1573-6881 .- 0145-479X. ; 48:3, s. 269-279
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiac arrest (CA) results in a sepsis-like syndrome with activation of the innate immune system and increased mitochondrial bioenergetics.OBJECTIVE: To determine if platelet mitochondrial respiration increases following CA in a porcine pediatric model of asphyxia-associated ventricular fibrillation (VF) CA, and if this readily obtained biomarker is associated with decreased brain mitochondrial respiration. CA protocol: 7 min of asphyxia, followed by VF, protocolized titration of compression depth to systolic blood pressure of 90 mmHg and vasopressor administration to a coronary perfusion pressure greater than 20 mmHg.PRIMARY OUTCOME: platelet integrated mitochondrial electron transport system (ETS) function evaluated pre- and post-CA/ROSC four hours after return of spontaneous circulation (ROSC). Secondary outcome: correlation of platelet mitochondrial bioenergetics to cerebral bioenergetic function. Platelet maximal oxidative phosphorylation (OXPHOSCI+CII), P < 0.02, and maximal respiratory capacity (ETSCI+CII), P < 0.04, were both significantly increased compared to pre-arrest values. This was primarily due to a significant increase in succinate-supported respiration through Complex II (OXPHOSCII, P < 0.02 and ETSCII, P < 0.03). Higher respiration was not due to uncoupling, as the LEAKCI + CII respiration (mitochondrial respiration independent of ATP-production) was unchanged after CA/ROSC. Larger increases in platelet mitochondrial respiratory control ratio (RCR) compared to pre-CA RCR were significantly correlated with lower RCRs in the cortex (P < 0.03) and hippocampus (P < 0.04) compared to sham respiration. Platelet mitochondrial respiration is significantly increased four hours after ROSC. Future studies will identify mechanistic relationships between this serum biomarker and altered cerebral bioenergetics function following cardiac arrest.
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43.
  • Fitzpatrick, John M., et al. (författare)
  • Optimizing treatment for men with advanced prostate cancer : expert recommendations and the multidisciplinary approach
  • 2008
  • Ingår i: Critical reviews in oncology/hematology. - : Elsevier BV. - 1040-8428 .- 1879-0461. ; 68:Suppl.1, s. S9-S22
  • Forskningsöversikt (refereegranskat)abstract
    • A multidisciplinary panel of 20 international experts, including urologists, radiation oncologists, and medical oncologists, convened during the Advanced Prostate Cancer Multidisciplinary Team meeting in Rome, Italy, in January 2007, to discuss the multidisciplinary team approach and current patterns of care for patients with hormone-refractory prostate cancer (HRPC). During the meeting, the experts discussed several definitions currently used in prostate cancer management, including those for senior adult patients. In addition, the panel reviewed a series of patient case studies in order to provide feedback on current treatment practices and to identify possible strategies for best practice. It was stressed that treatment decisions for senior adult patients should not be based solely on patient age. Additionally, although historically treatment decisions for advanced prostate cancer have focused on palliative care, given the survival benefit associated with docetaxel-based chemotherapy across patient subgroups, more men are likely to be offered chemotherapy for advanced-stage disease in the future.
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44.
  • Garmestani, Ahjond, et al. (författare)
  • Untapped capacity for resilience in environmental law
  • 2019
  • 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. ; 116:40, s. 19899-19904
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the past several decades, environmental governance has made substantial progress in addressing environmental change, but emerging environmental problems require new innovations in law, policy, and governance. While expansive legal reform is unlikely to occur soon, there is untapped potential in existing laws to address environmental change, both by leveraging adaptive and transformative capacities within the law itself to enhance social-ecological resilience and by using those laws to allow social-ecological systems to adapt and transform. Legal and policy research to date has largely overlooked this potential, even though it offers a more expedient approach to addressing environmental change than waiting for full-scale environmental law reform. We highlight examples from the United States and the European Union of untapped capacity in existing laws for fostering resilience in social-ecological systems. We show that governments and other governance agents can make substantial advances in addressing environmental change in the short term-without major legal reform-by exploiting those untapped capacities, and we offer principles and strategies to guide such initiatives.
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45.
  • Hayes, Steven C., et al. (författare)
  • Report of the ACBS Task Force on the strategies and tactics of contextual behavioral science research
  • 2021
  • Ingår i: Journal of Contextual Behavioral Science. - : Elsevier. - 2212-1447. ; 20, s. 172-183
  • Tidskriftsartikel (refereegranskat)abstract
    • Throughout its history the strategy and tactics of contextual behavioral science (CBS) research have had distinctive features as compared to traditional behavioral science approaches. Continued progress in CBS research can be facilitated by greater clarity about how its strategy and tactics can be brought to bear on current challenges. The present white paper is the result of a 2 1/2-year long process designed to foster consensus among representative producers and consumers of CBS research about the best strategic pathway forward. The Task Force agreed that CBS research should be multilevel, process-based, multidimensional, prosocial, and pragmatic, and provided 33 recommendations to the CBS community arranged across these characteristics. In effect, this report provides a detailed research agenda designed to maximize the impact of CBS as a field. Scientists and practitioners are encouraged to mount this ambitious agenda.
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46.
  • Hollyfield, Shakira, et al. (författare)
  • An Observational Study of Outcomes Associated With Virtual Pain Management Programs Based on Acceptance and Commitment Therapy Implemented During the COVID-19 Pandemic
  • 2023
  • Ingår i: The Clinical Journal of Pain. - : Wolters Kluwer. - 0749-8047 .- 1536-5409. ; 39:10, s. 524-536
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: In response to COVID-19, virtual, group-based interdisciplinary pain management programs (PMPs) were rapidly implemented. This included implementing different intensities and formats of virtual PMPs to address a range of patient needs and complexity. This observational study investigated outcomes associated with virtual high and low-intensity and pre-neuromodulation PMPs based on acceptance and commitment therapy as part of routine care during the pandemic.Methods: Depending on patients’ needs, participants completed a virtual high-intensity or low-intensity PMP, or a virtual PMP in preparation for neuromodulation, from June 2020 to June 2022. Participants completed standardized measures of pain intensity and interference, work and social adjustment, depression, and pain acceptance before and after treatment. Data from 2018 to 2019 for in-person residential (n=561), outpatient (n=123), and pre-neuromodulation (n=207) PMPs were also examined to provide a historical benchmark of performance.Results: The virtual high-intensity PMP (n=294) showed significant improvements in all variables, with small effects. There were significant improvements with small effects for pain interference, depression, and acceptance for the virtual pre-neuromodulation PMP (n=129). No statistically significant improvements were observed for the virtual low-intensity PMP (n=90). The improvements associated with prepandemic in-person PMPs were generally larger relative to the virtual PMPs of comparable intensity delivered during the pandemic.Discussion: These data provide preliminary support for the potential benefits of high, but not low, intensity virtual acceptance and commitment therapy-based PMPs, including in the context of neuromodulation. Research is needed to maximize the impact of virtual PMPs and match patients with the most appropriate delivery format.
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47.
  • Holmes, Melissa N. Galea, et al. (författare)
  • Experiences of training and delivery of Physical therapy informed by Acceptance and Commitment Therapy (PACT) : a longitudinal qualitative study
  • 2021
  • Ingår i: Physiotherapy. - : Elsevier. - 0031-9406 .- 1873-1465. ; 112, s. 41-48
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Physiotherapy informed by Acceptance and Commitment Therapy (PACT) is a novel intervention that is related to improved disability and functioning in people with chronic lowback pain. This study explored physiotherapists experiences over time of the PACT training programme and intervention delivery. Design A longitudinal qualitative study using semi-structured, in-depth, individual interviews at three time points was conducted. Methods A phenomenological approach underpinned the methods. Interviews followed topic-guides developed a priori. Transcribed interviews were coded inductively to generate themes. Data were member checked by participants and validated by two researchers. Participants Eight clinical physiotherapists from three secondary care centres in the United Kingdom (n = 5 female; age, 24 to 44 years; duration of practice, 3 to 14 years) were included. Results Five themes emerged from the data. Experiential learning techniques were challenging but valued because they bridged theoretical principles and concepts with practice. Ongoing individual and group supervision was beneficial, but required tailoring and tapering. PACT delivery extended physiotherapy skills and practice, including techniques that acknowledged and addressed patient treatment expectations. With experience, participants desired greater flexibility and autonomy to tailor PACT delivery. Conclusions PACT training and delivery were acceptable to physiotherapists. Existing skills were developed and additional, applicable approaches were provided that addressed psychosocial and behavioural aspects of chronic low back pain. (c) 2021 Chartered Society of Physiotherapy. 
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48.
  • Kanzler, Kathryn E, et al. (författare)
  • Mitigating the Effect of Pain Severity on Activity and Disability in Patients with Chronic Pain : The Crucial Context of Acceptance.
  • 2018
  • Ingår i: Pain medicine (Malden, Mass.). - : Oxford University Press (OUP). - 1526-2375 .- 1526-4637.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The purpose of this study was to examine the effect of pain severity on activity levels and physical disability in the context of high pain acceptance. We hypothesized that pain acceptance moderates the effect of pain severity on general activity and physical disability, such that at higher levels of acceptance, the deleterious effect of pain is mitigated.Methods: Two hundred seven patients with chronic pain were recruited from three clinics in a large southwestern military treatment facility. Participants completed an anonymous self-report battery of standardized measures, including the Chronic Pain Acceptance Questionnaire, modified Oswestry Disability Index, and Pain Severity and General Activity subscales of the West Haven-Yale Multidimensional Pain Inventory.Results: Chronic pain acceptance was found to significantly moderate relations between pain severity and general activity (b  =  0.0061, t(198) = 2.75, P = 0.007, 95% confidence interval [CI] = 0.002 to 0.011) and pain severity and disability (b  =  0.036, t(193) = -2.564, P = 0.011, 95% CI = -0.063 to -0.008). In the context of higher acceptance, the negative effect of pain on activity and disability appeared reduced. Conversely, in the context of low acceptance, the effect of pain on disability appeared accentuated at all levels of pain severity.Conclusions: Higher acceptance mitigated both activity level and disability in a military-affiliated clinical sample of patients with chronic pain. Results further establish the role of acceptance in relation to functioning in a unique sample of people with chronic pain. These findings have implications for understanding and enhancing functioning in chronic pain populations.
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49.
  • Karayannis, Nicholas Vasilis., et al. (författare)
  • Pain acceptance and psychological inflexibility predict pain interference outcomes for persons with chronic pain receiving pain psychology
  • 2023
  • Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 23:3, s. 464-475
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Awareness (being present), acceptance, and engagement (committed action) are three dimensions of psychological flexibility. Understanding these in the context of chronic pain may identify treatment targets to help refine individual treatment. Our objective was to test the predictive capacity of three dimensions within the psychological flexibility model on the longitudinal trajectory of pain interference.Methods: Patients receiving pain psychology treatment at a pain management center participated in this pragmatic clinical longitudinal study (n=86 with at least three assessments; Mean age=51 years; Gender=60 females, 26 males). Measures included the Five Facet Mindfulness Questionnaire (FFMQ-SF); Chronic Pain Acceptance Questionnaire (CPAQ-8); Psychological Inflexibility in Pain Scale (PIPS-12); and Committed Action Questionnaire (CAQ-8). The dependent variable was the Patient Reported Outcomes Information System (PROMIS) Pain Interference (PI). We used latent growth modelling to analyze scores assessed within 180 days of patient care.Results: Psychological inflexibility (PIPS-12) and pain acceptance (CPAQ-8) measured at baseline predicted PI outcomes (n=86). PIPS-12 showed a direct relationship with pain interference (PI), where higher PIPS-12 scores predicted significantly higher PI mean scores on average across the study period (ρ=0.422, r2=0.382) but also predicted significantly greater decreases in PI across time (ρ=−0.489, r2=0.123). Higher CPAQ-8 scores predicted significantly lower PI mean scores on average across the study period (ρ=−0.478, r2=0.453) but also significantly smaller decreases in PI across time (ρ=0.495, r2=0.076). Awareness (FFMQ-SF) and engagement (CAQ-8) were not predictive of PI outcomes.Conclusions: Patients who entered pain psychology treatment with lower pain acceptance and higher psychological inflexibility showed the largest reductions in pain interference across time. These results contribute towards a novel prognostic understanding of the predictive roles of an enhancing dimension and limiting dimension of psychological flexibility.
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50.
  • Kilic, Aysenur, et al. (författare)
  • A 12-month longitudinal study examining the shared and unique contributions of self-compassion and psychological inflexibility to distress and quality of life in people with Type 2 Diabetes
  • 2022
  • Ingår i: Journal of Psychosomatic Research. - : Elsevier. - 0022-3999 .- 1879-1360. ; 155
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Self-compassion and psychological flexibility appear to benefit wellbeing and quality of life (QoL) in the general population and in people with long-term conditions like Type 2 Diabetes (T2D). However, both variables share similarities and their unique roles in relation to distress and QoL in people with diabetes over time are not clear.Design: This was a longitudinal study with online assessments of self-compassion, psychological inflexibility, distress (depression, anxiety, diabetes-distress), and QoL at baseline (T1) and six (T2) and 12 months (T3). Methods: In total, 173 UK adults with T2D completed baseline questionnaires; T2 and T3 follow-ups were completed by 82 and 52 participants, respectively. Correlations were conducted to understand the relationships between variables at each time point. Hierarchical regressions were conducted to understand the unique predictive role of baseline self-compassion and psychological inflexibility in relation to distress and QoL at T2 and T3, controlling for age and baseline distress and QoL.Results: There were large significant negative correlations between self-compassion and psychological inflexibility (r >-0.50), and both had significant large correlations with distress (r >-0.50) but not QoL across time points. Regressions indicated that psychological inflexibility uniquely predicted depression (T2) and anxiety symptoms (T2 and T3) and QoL (T3). Self-compassion did not uniquely predict any of the outcomes.Conclusions: Psychological inflexibility may play an important role in distress in T2D, but prospective studies with larger samples are needed to replicate these findings. Given the overlap between psychological inflexibility and self-compassion, treatments targeting either variable may be useful.
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