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1.
  • De Leoz, M. L. A., et al. (author)
  • NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
  • 2020
  • In: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
  • Journal article (peer-reviewed)abstract
    • A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
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  • Byrne, Julianne, et al. (author)
  • The PanCareSurFup consortium : research and guidelines to improve lives for survivors of childhood cancer
  • 2018
  • In: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 103:Nov, s. 238-248
  • Journal article (peer-reviewed)abstract
    • Background: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. Methods: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. Results: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case-control studies of subsequent malignancies and cardiac disease in 5-year survivors. Conclusions: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health.
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  • Bouwman, Eline, et al. (author)
  • Healthcare professionals' perceived barriers and facilitators of health behavior support provision : A qualitative study
  • 2023
  • In: Cancer Medicine. - : Wiley. - 2045-7634. ; 12:6, s. 7414-7426
  • Journal article (peer-reviewed)abstract
    • Background: Childhood cancer survivors (CCSs) have an increased risk of developing chronic health conditions. Evidence suggests that poor health behaviors further increase health risks. Healthcare professionals (HCPs) involved in survivorship care have a key role in providing health behavior support (HBS) but can feel limited in their ability to do so. This study aims to explore European HCPs perceived facilitators and barriers to providing HBS to CCSs. Methods: Five focus groups with 30 HCPs from survivorship care clinics across Europe were conducted. Topic guides were informed by the Theoretical Domains Framework (TDF) to capture domains that may influence provision of HBS. Focus groups were analyzed with thematic analysis. Transcripts were inductively coded, after which axial coding was applied to organize codes into categories. Finally, categories were mapped onto the TDF domains. Results: Nine TDF domains were identified in the data. The most commonly reported TDF domains were “Knowledge”, “Skills”, and “Environmental context and resources”. HCPs indicated that their lack of knowledge of the association between late effects and health behaviors, besides time restrictions, were barriers to HBS. Facilitators for HBS included possession of skills needed to pass on health behavior information, good clinic organization, and an established network of HCPs. Conclusions: This study identified education and training of HCPs as key opportunities to improve HBS. Survivorship care clinics should work towards establishing well-integrated structured care with internal and external networks including HBS being part of routine care. Proper understanding of facilitators and barriers should lead to better survivorship care for CCSs.
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  • Falck, Felicitas A O K, et al. (author)
  • Subjective Experiences of Pregnancy, Delivery, and Nursing in Transgender Men and Non-Binary Individuals : A Qualitative Analysis of Gender and Mental Health Concerns
  • 2024
  • In: Archives of Sexual Behavior. - 0004-0002 .- 1573-2800. ; 53:5, s. 1981-2002
  • Journal article (peer-reviewed)abstract
    • Studies of how gender-diverse individuals experience pregnancy, childbirth, and nursing remain few, mainly focus on the US and contain scarce information about mental health concerns peri-partum. This hinders informed reproductive health decisions and counseling. We used in-depth interviews to examine how gestational gender-diverse individuals in Sweden experience the process of planning and undergoing pregnancy, delivery, and nursing. In total, 12 participants, identifying on the masculine side of the gender spectrum or as non-binary, who had attended Swedish antenatal care and delivered a live birth, were included in the study. Data were analyzed using qualitative thematic content analysis. The analysis resulted in one overarching theme: sustaining gender congruence during pregnancy and three main categories: (1) considering pregnancy; (2) undergoing pregnancy and childbirth; and (3) postnatal reflections. The association between childbearing and being regarded as female permeated narratives. Participants renegotiated the feminine connotations of pregnancy, accessed gender-affirming treatment, and concealed their pregnancy to safeguard their gender congruence. Mis-gendering and breast enlargement triggered gender dysphoria. Social judgment, loneliness, information shortages, hormonal influence and cessation of testosterone increased gender dysphoria and strained their mental health. Depression exacerbated gender dysphoria and made it harder to claim one's gender identity. Dissociation was used to handle a feminized body, vaginal delivery, and nursing. Pregnancy was easier to envision and handle after masculinizing gender-affirming treatments. The results deepen the understanding of gender dysphoria and may be used to inform reproductive counseling and healthcare development. Research outcomes on mental health concerns provide a basis for further research.
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  • Grabow, Desiree, et al. (author)
  • The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer : a cohort from 12 European countries
  • 2018
  • In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 33:3, s. 335-349
  • Journal article (peer-reviewed)abstract
    • Childhood cancer survivors face risks from a variety of late effects, including cardiac events, second cancers, and late mortality. The aim of the pan-European PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies (PanCareSurFup) Consortium was to collect data on incidence and risk factors for these late effects among childhood cancer survivors in Europe. This paper describes the methodology of the data collection for the overall PanCareSurFup cohort and the outcome-related cohorts. In PanCareSurFup 13 data providers from 12 countries delivered data to the data centre in Mainz. Data providers used a single variable list that covered all three outcomes. After validity and plausibility checks data was provided to the outcome-specific working groups. In total, we collected data on 115,596 patients diagnosed with cancer from 1940 to 2011, of whom 83,333 had survived 5 years or more. Due to the eligibility criteria and other requirements different numbers of survivors were eligible for the analysis of each of the outcomes. Thus, 1014 patients with at least one cardiac event were identified from a cohort of 39,152 5-year survivors; for second cancers 3995 survivors developed at least one second cancer from a cohort of 71,494 individuals, and from the late mortality cohort of 79,441 who had survived at least 5 years, 9247 died subsequently. Through the close cooperation of many European countries and the establishment of one central data collection and harmonising centre, the project succeeded in generating the largest cohort of children with cancer to date.
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  • Byrne, Julianne, et al. (author)
  • Impact of era of diagnosis on cause-specific late mortality among 77 423 five-year European survivors of childhood and adolescent cancer : The PanCareSurFup consortium
  • 2022
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 150:3, s. 406-419
  • Journal article (peer-reviewed)abstract
    • Late mortality of European 5-year survivors of childhood or adolescent cancer has dropped over the last 60 years, but excess mortality persists. There is little information concerning secular trends in cause-specific mortality among older European survivors. PanCareSurFup pooled data from 12 cancer registries and clinics in 11 European countries from 77 423 five-year survivors of cancer diagnosed before age 21 between 1940 and 2008 followed for an average age of 21 years and a total of 1.27 million person-years to determine their risk of death using cumulative mortality, standardized mortality ratios (SMR), absolute excess risks (AER), and multivariable proportional hazards regression analyses. At the end of follow-up 9166 survivors (11.8%) had died compared to 927 expected (SMR 9.89, 95% confidence interval [95% CI] 9.69-10.09), AER 6.47 per 1000 person-years, (95% CI 6.32-6.62). At 60 to 68 years of attained age all-cause mortality was still higher than expected (SMR = 2.41, 95% CI 1.90-3.02). Overall cumulative mortality at 25 years from diagnosis dropped from 18.4% (95% CI 16.5-20.4) to 7.3% (95% CI 6.7-8.0) over the observation period. Compared to the diagnosis period 1960 to 1969, the mortality hazard ratio declined for first neoplasms (P for trend <.0001) and for infections (P <.0001); declines in relative mortality from second neoplasms and cardiovascular causes were less pronounced (P =.1105 and P =.0829, respectively). PanCareSurFup is the largest study with the longest follow-up of late mortality among European childhood and adolescent cancer 5-year survivors, and documents significant mortality declines among European survivors into modern eras. However, continuing excess mortality highlights survivors' long-term care needs.
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  • Falck-Ytter, Terje, et al. (author)
  • The Babytwins Study Sweden (BATSS): A Multi-Method Infant Twin Study of Genetic and Environmental Factors Influencing Infant Brain and Behavioral Development
  • 2021
  • In: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 24:4, s. 217-227
  • Journal article (peer-reviewed)abstract
    • Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5-36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years.
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  • Hedegaard, Jakob, et al. (author)
  • Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
  • 2016
  • In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
  • Journal article (peer-reviewed)abstract
    • Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
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  • Kieran, Mark W., et al. (author)
  • A global approach to long-term follow-up of targeted and immune-based therapy in childhood and adolescence
  • 2021
  • In: Pediatric Blood and Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 68:7
  • Journal article (peer-reviewed)abstract
    • While considerable efforts and progress in our understanding of the long-term toxicities of surgery, radiation and chemotherapy in children with cancer have been made over the last 5 decades, there continues to be a wide gap in our knowledge of the long-term health impact of most novel targeted and immunotherapy agents. To address this gap, ACCELERATE, a multi-stakeholder collaboration of clinical and translational academics, regulators from the EMA and FDA, patient/family advocates and members spanning small biotechnology through to large pharmaceutical companies have initiated the development of an international long-term follow-up data registry to collect this important information prospectively. Providing critical safety data on the long-term use of these approved and investigational therapies in children will support the regulatory requirements and labeling information. It will also provide the necessary insight to help guide physicians and families on the appropriateness of a targeted or immune therapy for their child and inform survivorship planning.
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  • Mason, L., et al. (author)
  • Preference for biological motion is reduced in ASD : implications for clinical trials and the search for biomarkers
  • 2021
  • In: Molecular Autism. - : Springer Nature. - 2040-2392. ; 12
  • Journal article (peer-reviewed)abstract
    • Background: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology.Methods: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL).Results: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline.Limitations: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons.Conclusions: Biological motion preference elicits small-to-medium-sized case–control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear.
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  • Olsen, Are, 1972, et al. (author)
  • Overview of the Nordic Seas CARINA data and salinity measurements
  • 2009
  • In: Earth System Science Data Discussions. - 1866-3591. ; 2, s. 1-25
  • Journal article (peer-reviewed)abstract
    • Water column data of carbon and carbon relevant hydrographic and hydrochemical parameters from 188 previously non-publicly available cruises in the Arctic, Atlantic, and Southern Ocean have been retrieved and merged into a new database: CARINA (CARbon IN the Atlantic). The data have been subject to rigorous quality control (QC) in order to ensure highest possible quality and consistency. The data for most of the parameters included were examined in order to quantify systematic biases in the reported values, i.e. secondary quality control. Significant biases have been corrected for in the data products, i.e. the three merged files with measured, calculated and interpolated values for each of the three CARINA regions; the Arctic Mediterranean Seas (AMS), the Atlantic (ATL) and the Southern Ocean (SO). With the adjustments the CARINA database is consistent both internally as well as with GLODAP (Key et al., 2004) and is suitable for accurate assessments of, for example, oceanic carbon inventories and uptake rates and for model validation. The Arctic Mediterranean Seas includes the Arctic Ocean and the Nordic Seas, and the quality control was carried out separately in these two areas. This contribution provides an overview of the CARINA data from the Nordic Seas and summarises the findings of the QC of the salinity data. One cruise had salinity data that were of questionable quality, and these have been removed from the data product. An evaluation of the consistency of the quality controlled salinity data suggests that they are consistent to at least 0.05.
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  • Pijl, M. K. J., et al. (author)
  • Parent-child interaction during the first year of life in infants at elevated likelihood of autism spectrum disorder
  • 2021
  • In: Infant Behavior and Development. - : Elsevier. - 0163-6383 .- 1879-0453 .- 1934-8800. ; 62
  • Journal article (peer-reviewed)abstract
    • Autism spectrum disorder (ASD) likely emerges from a complex interaction between pre-existing neurodevelopmental vulnerabilities and the environment. The interaction with parents forms a key aspect of an infant’s social environment, but few prospective studies of infants at elevated likelihood (EL) for ASD (who have an older sibling with ASD) have examined parent-child interactions in the first year of life. As part of a European multisite network, parent-child dyads of free play were observed at 5 months (62 EL infants, 47 infants at typical likelihood (TL)) and 10 months (101 EL siblings, 77 TL siblings). The newly-developed Parent-Infant/Toddler Coding of Interaction (PInTCI) scheme was used, focusing on global characteristics of infant and parent behaviors. Coders were blind to participant information. Linear mixed model analyses showed no significant group differences in infant or parent behaviors at 5 or 10 months of age (all ps≥0.09, d≤0.36), controlling for infant’s sex and age, and parental educational level. However, without adjustments, EL infants showed fewer and less clear initiations at 10 months than TL infants (p = 0.02, d = 0.44), but statistical significance was lost after controlling for parental education (p = 0.09, d = 0.36), which tended to be lower in the EL group. Consistent with previous literature focusing on parent-infant dyads, our findings suggest that differences between EL and TL dyads may only be subtle during the first year of life. We discuss possible explanations and implications for future developmental studies.
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  • van Kalsbeek, Rebecca J., et al. (author)
  • The PanCareFollowUp Care Intervention : A European harmonised approach to person-centred guideline-based survivorship care after childhood, adolescent and young adult cancer
  • 2022
  • In: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 162, s. 34-44
  • Journal article (peer-reviewed)abstract
    • Background: Long-term follow-up (LTFU) care, although endorsed, is not available for the majority of adult survivors of childhood, adolescence and young adult (CAYA) cancer. Barriers to implementation include lack of time, knowledge, personnel and funding. Sustainable solutions are urgently needed to address the needs of CAYA cancer survivors to improve the quality of life and reduce the burden of late effects on survivors, health care systems and society. The European Union–funded PanCareFollowUp project, initiated by the Pan-European Network for Care of Survivors after Childhood and Adolescent Cancer, was established to facilitate the implementation of person-centred survivorship care across Europe. Patients and methods: The PanCareFollowUp Care Intervention was co-developed with survivors as part of the PanCareFollowUp project. It is a person-centred approach to survivorship care, supported by guidelines and with flexibility to adapt to local health care settings. The Care Intervention consists of three steps: (1) previsit completion of a Survivor Questionnaire (by the survivor) and Treatment Summary (by the health care provider [HCP]), (2) a clinic visit including shared decision-making, and (3) a follow-up call to finalise the individualised Survivorship Care Plan. Results: We developed the key components of the PanCareFollowUp Care Intervention: a PanCareFollowUp Survivor Questionnaire, Treatment Summary template, Survivorship Care Plan template, and educational materials for HCPs and survivors. Wide implementation of the PanCareFollowUp Care Intervention will be supported with a freely distributed Replication Manual on completion of the PanCareFollowUp project. Conclusions: The PanCareFollowUp Care Intervention will support the implementation of person-centred, guideline-based LTFU care in different health care settings across Europe to improve survivors’ health and well-being.
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  • Brownlie, D, et al. (author)
  • Comparison of Lung-Homing Receptor Expression and Activation Profiles on NK Cell and T Cell Subsets in COVID-19 and Influenza
  • 2022
  • In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 834862-
  • Journal article (peer-reviewed)abstract
    • Respiratory viral infections with SARS-CoV-2 and influenza viruses commonly induce a strong infiltration of immune cells into the human lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of circulating lymphocytes in the lung, rather little is known about how peripheral blood natural killer (NK) cell and T cell subsets are equipped for lung-homing in COVID-19 and influenza. Here, we provide a detailed comparative analysis of NK cells and T cells in patients infected with SARS-CoV-2 or influenza virus, focusing on the protein and gene expression of chemokine receptors known to be involved in recruitment to the lung. For this, we used 28-colour flow cytometry as well as re-analysis of a publicly available single-cell RNA-seq dataset from bronchoalveolar lavage (BAL) fluid. Frequencies of NK cells and T cells expressing CXCR3, CXCR6, and CCR5 were altered in peripheral blood of COVID-19 and influenza patients, in line with increased transcript expression of CXCR3, CXCR6, and CCR5 and their respective ligands in BAL fluid. NK cells and T cells expressing lung-homing receptors displayed stronger phenotypic signs of activation compared to cells lacking lung-homing receptors, and activation was overall stronger in influenza compared to COVID-19. Together, our results indicate a role for CXCR3+, CXCR6+, and/or CCR5+ NK cells and T cells that potentially migrate to the lungs in moderate COVID-19 and influenza patients, identifying common targets for future therapeutic interventions in respiratory viral infections.
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  • Falck, Emma, et al. (author)
  • Interaction of fusidic acid with lipid membranes: Implications to the mechanism of antibiotic activity
  • 2006
  • In: Biophysical Journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 91:5, s. 1787-1799
  • Journal article (peer-reviewed)abstract
    • We have studied the effects of cholesterol and steroid-based antibiotic fusidic acid (FA) on the behavior of lipid bilayers using a variety of experimental techniques together with atomic-scale molecular dynamics simulations. Capillary electrophoretic measurements showed that FA was incorporated into fluid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membranes. Differential scanning calorimetry in turn showed that FA only slightly altered the thermodynamic properties of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers, whereas cholesterol abolished all endotherms when the mole fraction of cholesterol (X-chol) was > 0.20. Fluorescence spectroscopy was then used to further characterize the influence of these two steroids on DPPC large unilamellar vesicles. In the case of FA, our result strongly suggested that FA was organized into lateral microdomains with increased water penetration into the membrane. For cholesterol/DPPC mixtures, fluorescence spectroscopy results were compatible with the formation of the liquid-ordered phase. A comparison of FA and cholesterol-induced effects on DPPC bilayers through atomistic molecular dynamics simulations showed that both FA and cholesterol tend to order neighboring lipid chains. However, the ordering effect of FA was slightly weaker than that of cholesterol, and especially for deprotonated FA the difference was significant. Summarizing, our results show that FA is readily incorporated into the lipid bilayer where it is likely to be enriched into lateral microdomains. These domains could facilitate the association of elongation actor-G into lipid rafts in living bacteria, enhancing markedly the antibiotic efficacy of FA.
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  • Hendry, Alexandra, et al. (author)
  • Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits
  • 2020
  • In: Journal of autism and developmental disorders. - : Springer Nature. - 0162-3257 .- 1573-3432. ; 50:11, s. 4085-4105
  • Journal article (peer-reviewed)abstract
    • Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.
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  • Kennedy, Daniel P., et al. (author)
  • Genetic Influence on Eye Movements to Complex Scenes at Short Timescales
  • 2017
  • In: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 27:22, s. 3554-3560
  • Journal article (peer-reviewed)abstract
    • Where one looks within their environment constrains one?s visual experiences, directly affects cognitive, emotional, and social processing [1?4], influences learning opportunities [5], and ultimately shapes one?s developmental path. While there is a high degree of similarity across individuals with regard to which features of a scene are fixated [6?8], large individual differences are also present, especially in disorders of development [9?13], and clarifying the origins of these differences is essential to understand the processes by which individuals develop within the complex environments in which they exist and interact. Toward this end, a recent paper [14] found that ?social visual engagement??namely, gaze to eyes and mouths of faces?is strongly influenced by genetic factors. However, whether genetic factors influence gaze to complex visual scenes more broadly, impacting how both social and non-social scene content are fixated, as well as general visual exploration strategies, has yet to be determined. Using a behavioral genetic approach and eye tracking data from a large sample of 11-year-old human twins (233 same-sex twin pairs; 51% monozygotic, 49% dizygotic), we demonstrate that genetic factors do indeed contribute strongly to eye movement patterns, influencing both one?s general tendency for visual exploration of scene content, as well as the precise moment-to-moment spatiotemporal pattern of fixations during viewing of complex social and non-social scenes alike. This study adds to a now growing set of results that together illustrate how genetics may broadly influence the process by which individuals actively shape and create their own visual experiences.
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  • Laring, Jonas, 1951, et al. (author)
  • Simulation for manufacturing engineering (ViPP)
  • 2005
  • In: SAE Technical Papers. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191 .- 2688-3627. ; Digital Human Modeling for Design and Engineering Symposium
  • Journal article (peer-reviewed)abstract
    • The aim of this project is to develop methodologies and supportive tools to handle introduction and administration of ergonomics simulation tools for manufacturing engineering. The main result will be a web-based handbook for effective use of digital human modelling tools inside companies and between suppliers and companies. ViPP is divided in three parts: Part A: Studies will be done with the purpose to advise on proper content of input data and on method for assessment of simulations' results. Part B: Studies will be done in order to check reliability of used digital human tools: (1) intra- and inter-individual differences concerning simulation results, (2) vision analysis and (3) the importance of the digital human model appearance/representation on simulation results. Part C: A handbook will be written on virtual production planning for pre production engineers, designers and decision makers. Copyright © 2005 SAE International.
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  • Martinez-Aparicio, Carmen, et al. (author)
  • Nerve conduction study of the three supraclavicular nerve branches
  • 2018
  • In: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 58:2, s. 300-303
  • Journal article (peer-reviewed)abstract
    • Introduction: We describe a new nerve conduction study technique with reference values for the 3 branches of the supraclavicular nerve (SCN) in young healthy subjects and application of it in 2 patients.Methods: The recording electrode was placed on the posterior border of the sternocleidomastoid muscle, 6–7 cm from the sternoclavicular joint. SCN branches were stimulated below the clavicle, 2.5, 7, and 10.5 cm lateral to the sternoclavicular joint.Results: Twenty healthy volunteers (10 men), 19–38 years, mean 25.9 years (SD 6.3), and 2 patients with SCN lesions were studied. The mean conduction velocities of the SCN branches were 70–78 m/s (SD 8–10 m/s), and amplitudes 3–4 µV (SD 0.9–2.0 µV). There were no side‐to‐side or gender differences.Discussion: The 3 SCN branches could be studied in all subjects. We provide reference values for young subjects. This new method was useful in verifying SCN lesions in 2 patients.
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  • Ohlsson, R, et al. (author)
  • PDGFB regulates the development of the labyrinthine layer of the mouse fetal placenta.
  • 1999
  • In: Dev Biol. - : Elsevier BV. - 0012-1606. ; 212:1, s. 124-36
  • Journal article (peer-reviewed)abstract
    • PDGFB is a growth factor which is vital for the completion of normal prenatal development. In this study, we report the phenotypic analysis of placentas from mouse conceptuses that lack a functional PDGFB or PDGFRbeta gene. Placentas of both types of mutant exhibit changes in the labyrinthine layer, including dilated embryonic blood vessels and reduced numbers of both pericytes and trophoblasts. These changes are seen from embryonic day (E) 13.5, which coincides with the upregulation of PDGFB mRNA levels in normal placentas. By E17, modifications in shape, size, and number of the fetal blood vessels in the mutant placentas cause an abnormal ratio of the surface areas between the fetal and the maternal blood vessels in the labyrinthine layer. Our data suggest that PDGFB acts locally to contribute to the development of the labyrinthine layer of the fetal placenta and the formation of a proper nutrient-waste exchange system during fetal development. We point out that the roles of PDGFB/Rbeta signaling in the placenta may be analogous to those in the developing kidney, by controlling pericytes in the labyrinthine layer and mesangial cells in the kidney.
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49.
  • Siqueiros Sanchez, Monica, et al. (author)
  • Visual Disengagement : Genetic Architecture and Relation to Autistic Traits in the General Population
  • 2020
  • In: Journal of autism and developmental disorders. - : Springer Nature. - 0162-3257 .- 1573-3432. ; 50:6, s. 2188-2200
  • Journal article (peer-reviewed)abstract
    • Visual disengagement has been hypothesized as an endophenotype for autism. In this study we used twin modelling to assess the role of genetics in basic measures of visual disengagement, and tested their putative association to autistic traits in the general population. We used the Gap Overlap task in a sample of 492 twins. Results showed that most of the covariance among eye movement latencies across conditions was shared and primarily genetic. Further, there were unique genetic contributions to the Gap condition, but not to the Overlap condition—i.e. the one theorized to capture visual disengagement. We found no phenotypic association between autistic traits and disengagement, thus not supporting the hypothesis of visual disengagement as an endophenotype for autistic traits.
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50.
  • Siqueiros Sanchez, Monica, et al. (author)
  • Volitional eye movement control and ADHD traits : a twin study
  • 2020
  • In: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 61:12, s. 1309-1316
  • Journal article (peer-reviewed)abstract
    • BackgroundTop-down volitional command of eye movements may serve as a candidate endophenotype of ADHD, an important function underlying goal-directed action in everyday life. In this twin study, we examined the relation between performance on a response inhibition eye-tracking paradigm and parent-rated ADHD traits in a population-based twin sample. We hypothesized that altered eye movement control is associated with the severity of ADHD traits and that this association is attributable to genetic factors.MethodsA total of 640 twins (320 pairs, 50% monozygotic) aged 9–14 years) from the Child and Adolescent Twin Study in Sweden (CATSS) participated. Twins performed the antisaccade task indexing inhibitory alterations as either direction errors (following exogenous cues rather than instructions) or premature anticipatory eye movements (failure to wait for cues). We calculated the associations of eye movement control and ADHD traits using linear regression mixed-effects models and genetic and environmental influences with multivariate twin models.ResultsPremature anticipatory eye movements were positively associated with inattentive traits (β = .17; 95% CI: 0.04, 0.31), while controlling for hyperactive behaviors and other covariates. Both premature anticipatory eye movements and inattention were heritable (h2 = 0.40, 95% CI: 0.22, 0.56; h2 = 0.55; 95% CI: 0.42, 0.65; respectively), and their genetic correlation was small but statistically significant (r = .19, 95% CI: 0.02, 0.36). However, the genetic correlation did not remain significant after adjusting for covariates (age, sex, hyperactivity traits, IQ). No link was found between direction errors and ADHD traits.ConclusionsThis study indicates that there is a specific, genetically influenced, relation between top-down eye movement control and the inattentive traits typical of ADHD.
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