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2.
  • Cruz, Raquel, et al. (författare)
  • Novel genes and sex differences in COVID-19 severity
  • 2022
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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3.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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4.
  • Backes, Claudia, et al. (författare)
  • Production and processing of graphene and related materials
  • 2020
  • Ingår i: 2D Materials. - : IOP Publishing. - 2053-1583. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resource-consuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown. Section VIII discusses advances in GRM functionalization. A broad range of organic molecules can be anchored to the sp(2) basal plane by reductive functionalization. Negatively charged graphene can be prepared in liquid phase (e.g. via intercalation chemistry or electrochemically) and can react with electrophiles. This can be achieved both in dispersion or on substrate. The functional groups of GO can be further derivatized. Graphene can also be noncovalently functionalized, in particular with polycyclic aromatic hydrocarbons that assemble on the sp(2) carbon network by pi-pi stacking. In the liquid phase, this can enhance the colloidal stability of SLG/FLG. Approaches to achieve noncovalent on-substrate functionalization are also discussed, which can chemically dope graphene. Research efforts to derivatize CNMs are also summarized, as well as novel routes to selectively address defect sites. In dispersion, edges are the most dominant defects and can be covalently modified. This enhances colloidal stability without modifying the graphene basal plane. Basal plane point defects can also be modified, passivated and healed in ultra-high vacuum. The decoration of graphene with metal nanoparticles (NPs) has also received considerable attention, as it allows to exploit synergistic effects between NPs and graphene. Decoration can be either achieved chemically or in the gas phase. All LMs,
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5.
  • Bousquet, Jean, et al. (författare)
  • Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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6.
  • Menditto, Enrica, et al. (författare)
  • Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
  • 2019
  • Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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7.
  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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8.
  • Alarcon, Alvaro, et al. (författare)
  • All-in-Fiber Dynamically Reconfigurable Orbital Angular Momentum Mode Sorting
  • 2023
  • Ingår i: ACS Photonics. - : AMER CHEMICAL SOC. - 2330-4022. ; 10:10, s. 3700-3707
  • Tidskriftsartikel (refereegranskat)abstract
    • The orbital angular momentum (OAM) spatial degree of freedom of light has been widely explored in many applications, including telecommunications, quantum information, and light-based micromanipulation. The ability to separate and distinguish between the different transverse spatial modes is called mode sorting or mode demultiplexing, and it is essential to recover the encoded information in such applications. An ideal d mode sorter should be able to faithfully distinguish between the different d spatial modes, with minimal losses, and have d outputs and fast response times. All previous mode sorters rely on bulk optical elements, such as spatial light modulators, which cannot be quickly tuned and have additional losses if they are to be integrated with optical fiber systems. Here, we propose and experimentally demonstrate, to the best of our knowledge, the first all-in-fiber method for OAM mode sorting with ultrafast dynamic reconfigurability. Our scheme first decomposes the OAM mode in-fiber-optical linearly polarized (LP) modes and then interferometrically recombines them to determine the topological charge, thus correctly sorting the OAM mode. In addition, our setup can also be used to perform ultrafast routing of the OAM modes. These results show a novel and fiber-integrated form of optical spatial mode sorting that can be readily used for many new applications in classical and quantum information processing.
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9.
  • Borg, Alexander, et al. (författare)
  • Obesity is associated with pain and impaired mobility despite therapy in systemic lupus erythematosus
  • 2023
  • Ingår i: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate whether abnormal BMI is associated with health-related quality of life (HRQoL) impairments, defined as patient-reported problems within the different dimensions of the three-level EQ-5D (EQ-5D-3L), before and after treatment for active systemic lupus erythematosus (SLE).PATIENTS AND METHODS: We conducted a post-hoc analysis of data from two phase III clinical trials of belimumab in SLE, i.e., BLISS-52 (n = 865) and BLISS-76 (n = 819). Underweight was defined as BMI <18.5 kg/m2, normal weight as BMI ≥18.5 but <25 kg/m2, pre-obesity as BMI ≥25 but <30 kg/m2, and obesity as BMI ≥30 kg/m2. We investigated associations between BMI groups and problems (level 2 or 3) within each one of the five EQ-5D dimensions before treatment initiation and at week 52, using logistic regression analysis adjusting for age, ethnicity, disease activity, and glucocorticoid dose, and for the post-treatment analysis also for belimumab treatment and baseline EQ-5D-3L responses.RESULTS: Of 1,684 patients included, 73 (4%) were classified as underweight, 850 (50%) as normal weight, 438 (26%) as pre-obese, and 323 (19%) as obese. At baseline, obesity was associated with mild to severe problems in all EQ-5D dimensions (p < 0.05 for all), yielding the strongest association with problems in mobility (adjusted odds ratio, aOR: 2.1; 95% confidence interval, CI: 1.6-2.8; p < 0.001). Pre-obesity was also associated with problems in mobility (aOR: 1.4; 95% CI: 1.1-1.8; p = 0.005). Post-intervention, obesity was associated with problems in mobility and pain/discomfort, and pre-obesity with problems in mobility and self-care (p < 0.05 for all).CONCLUSION: Our study adds to the evidence that high BMI negatively affects SLE patients' HRQoL, with obesity being associated with pain and impaired mobility despite therapy.
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11.
  • Bousquet, Jean, et al. (författare)
  • ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
  • 2021
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
  • Forskningsöversikt (refereegranskat)abstract
    • Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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12.
  • Bousquet, J. Jean, et al. (författare)
  • Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
  • 2019
  • Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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13.
  • Castaño, Nicolas, et al. (författare)
  • Contrasting drivers of aboveground woody biomass and aboveground woody productivity in lowland forests of Colombia
  • 2024
  • Ingår i: Ecography. - 0906-7590 .- 1600-0587. ; 2024
  • Tidskriftsartikel (refereegranskat)abstract
    • The relative importance of abiotic and biotic factors in shaping forest biomass stocks and fluxes remains a controversial issue. Here, using data gathered from 39 1 ha plots located in flooded and terra firme mature tropical lowland forests of the Amazon and Orinoquia regions of Colombia, we evaluated the importance of climate, soil fertility, and flooding, as well as tree taxonomic/phylogenetic diversity and forest structural properties, in determining the aboveground biomass stocks (AGB; Mg ha−1) and aboveground woody productivity (AWP; Mg ha−1 year−1). Using information-theoretic multimodel inference and variance partitioning we found that forest structural features such as the number of trees with diameter at breast height ≥ 70 cm, and wood density, are the main drivers of variation in AGB. However, taxonomic diversity also contributes to AGB because it is associated with more large trees in these forests. In contrast, the key drivers of AWP in these forests were soil P and Mg concentrations, with no significant effects of diversity indices. These findings emphasize the need to include major soil cations other than N and P (e.g. Mg) in experimental studies to improve our understanding about the extent to which soil fertility can modulate increases in forest AWP due to climate change. Terra firme forests had higher AGB stocks than flooded forests, but both had similar AWP; and we found similar results for the drivers of AGB and AWP between flooded and terra firme forests. Our results provide limited evidence for strong effects of plant diversity on AGB or AWP. Therefore, we call for caution on generalizations of nature-based initiatives aiming to preserve diversity based on maximizing carbon stocks and productivity, due to the complex nature of the processes controlling carbon accumulation and carbon fluxes in tropical forests.
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14.
  • Emami, Nazanin, et al. (författare)
  • Ultra high molecular weight polyethylene based nano-composite in medical application: thermal, mechanical and tribological properties before and after aging and gama irradiation
  • 2016
  • Ingår i: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. - : Frontiers Media S.A..
  • Konferensbidrag (refereegranskat)abstract
    • Introduction: Osteolysis due the wear particles release at implant surfaces is one of the most important reasons for the failure of the polymer on metal implant devices in hip and knee prosthesis. Today the polymer on Metal/cermic composition is one of the most comon desgin used in clinic.Materials and Methods: In most of the polymer on metal (soft on hard) hip implant devices, Ultra High Molecular Weight Polyethylene (UHMWPE) is used as acetabluar liner. In the presented study, Surface functionalized Multi walled carbon nanotubes (MWCNTs), graphene oxide (GO) and nanodiamond (ND) were used to develop UHMWPE based nanocomposites. Effects of the reinforcement weight% were investigated (lowest of 0.1 wt% and highest of 2 wt% of different reinforcement were tested). Mechanical, thermal and tribological properties of different wt% of UHMWPE composites were characterised for all composites as manufactured, aged and gamma irradiated. The mentioned nanocomposites were compared to virgin UHMWPE as reference material. combination of ball milling and ultrasonication with controlled parameters were used to manufacture the nanocomposites.Results: In thermal properties, the degree of the crystalinity was not significantly affected, whereas the oxidation degradation was delayed significantly for as developed 3 different nanocomposites. The youngs’ modulus were increased by 10-15% for all nanocomposites and fracture stress reduced (from 0wt% to 0.5wt%) by 35%. Wear resistance was increased for UHMWPE/MWCNT nanocomposites at 0.5wt% for up to 30% and thereafter reduced when higher wt% of MWCNTs were added to the polymeric matrix. However, the UHMWPE/GO nanocompostes showed the maximum wear reduction at 2wt% of the reinforcement. For UHMWPE/ND nanocomposites, the wear mechanism showed the most improvement at 0.5 and 0.7 wt% of the reinforcement. The wear particles from wear tests for all different nano composites were collected and analysed via scanning electron microscopy (SEM). No significant differences in particle size distribution and shape among nanocomposites in comparison to the virgin UHMWPE were observed.   Gamma irradiation at 90 KGy affected the thermal, mechanical and tribological properties positively (in comparson to the virging UHMWPE). Whereas the aging reduced the wear resitance by 20% and tensile properties decreased by 30%. In general aging affected the performance of the nanocomposites negatively.Conclusion: Ball milling was successful method for preparation of nanocomposites. The addition of carbone based nano particles showed positive effect of thermal, mechanical and tribological properties of the developed nanocomposites in comparison to virgin UHMWPE.
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15.
  • Emamikia, Sharzad, et al. (författare)
  • Factors associated with non-adherence to medications in systemic lupus erythematosus : Results from a Swedish survey
  • 2024
  • Ingår i: Lupus. - : Sage Publications. - 0961-2033 .- 1477-0962. ; 33:6, s. 615-628
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To identify determinants of medication non-adherence in a Swedish population of systemic lupus erythematosus (SLE).METHODS: Patients with SLE from Karolinska and Örebro University Hospitals participated in a survey-based cross-sectional study. Demographics, disease activity, organ damage, HRQoL (LupusQol, EQ-5D-5 L), medication non-adherence (<80% on CQR-19 or MASRI) and beliefs about medicines (BMQ) were registered. MASRI was used to report adherence to different drugs/drug classes, categorised into (i) antimalarial agents (AMA), (ii) glucocorticoids and (iii) other SLE medications. Multivariable logistic regression adjusted for age, sex, disease activity and organ damage.RESULTS: Among 205 respondents, the median age was 52.0 years (IQR: 34.0-70.0), 86.3% were women, 66.8% were non-adherent to their medications according to CQR-19, and 6.6% and 6.3% were non-adherent to AMA and glucocorticoids, respectively, according to MASRI. Positive beliefs about glucocorticoids (OR; 95% CI: 0.77; 0.59-0.99; p = .039) and medications overall (0.71; 0.52-0.97; p = .029) were protective against non-adherence to glucocorticoids. Anxiety/depression (3.09; 1.12-8.54; p = .029), medication concerns (1.12; 1.05-1.20; p < .001) and belief that medications are overused (1.30; 1.15-1.46; p < .001) or harmful (1.36; 1.19-1.56; p < .001) were associated with medication non-adherence (CQR-19); beliefs in the necessity of medications (0.73; 0.65-0.82; p < .001) and positive beliefs in medications were protective (0.72; 0.60-0.86; p < .001). No associations were found between other investigated factors and medication non-adherence.CONCLUSIONS: Beliefs about medications were a major determinant of medication non-adherence. Patient education may help alleviate the negative impact of misinformation/unawareness on adherence.
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16.
  • Emamikia, Sharzad, et al. (författare)
  • Impact of remission and low disease activity on health-related quality of life in patients with systemic lupus erythematosus
  • 2022
  • Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 61:12, s. 4752-4762
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate the impact of remission and lupus low disease activity state (LLDAS) on health-related quality of life (HRQoL) in systemic lupus erythematosus.METHODS: SF-36, EQ-5D-3L and FACIT-Fatigue data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials were used. Duration in remission/LLDAS required to reach a HRQoL benefit ≥ minimal clinically important differences (MCIDs) during and post-treatment was determined using quantile regression and generalised estimating equations.RESULTS: Patients (N = 1684) were assessed every 4th week (15 visits). Four cumulative (β = 0.60) or four consecutive (β = 0.66) visits in remission were required to achieve a benefit ≥MCID in SF-36 physical component summary (PCS) scores, and six cumulative (β = 0.44) or five consecutive (β = 0.49) for a benefit ≥MCID in mental component summary (MCS) scores. Eight cumulative (β = 0.30 for both) or eight consecutive (β = 0.32 for both) visits in LLDAS were required for a benefit in PCS/MCS ≥MCID, respectively.For EQ-5D-3L index scores ≥MCID, six cumulative (β = 0.007) or five consecutive (β = 0.008) visits in remission were required, and eight cumulative (β = 0.005) or six consecutive (β = 0.006) visits in LLDAS. For FACIT-Fatigue scores ≥MCID, 12 cumulative (β = 0.34) or 10 consecutive (β = 0.39) visits in remission were required, and 17 cumulative (β = 0.24) or 16 consecutive (β = 0.25) visits in LLDAS.CONCLUSION: Remission and LLDAS contribute to a HRQoL benefit in a time-dependent manner. Shorter time in remission than in LLDAS was required for a clinically important benefit in HRQoL, and longer time in remission for a benefit in mental compared with physical HRQoL aspects. When remission/LLDAS was sustained, the same benefit was achieved in a shorter time.
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17.
  • Emamikia, Sharzad, et al. (författare)
  • The Impact of Remission and Low Disease Activity Attainment on Health-related Quality of Life in Two Phase III Clinical Trials of Belimumab in Systemic Lupus Erythematosus
  • 2021
  • Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 73:Suppl. 9, s. 2604-2606
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background/Purpose: Health- related quality of life (HRQoL) is considered one of the most important outcomes in clinical trials of systemic lupus erythematosus (SLE), along with reduction in disease activity and safety. We studied the duration and consecutiveness of remission or low disease activity throughout a 52- week long period on standard therapy plus belimumab or placebo in relation to HRQoL outcome.Methods: We analysed pooled 52- week data from the BLISS- 52 (N=865) and BLISS- 76 (N=819) phase III trials. We determined remission using the prevailing Definitions of Remission in SLE (DORIS) definition (1) and low disease activity using the Lupus Low Disease Activity State (LLDAS) (2). Remission required clinical (c)SLEDAI- 2K=0, PhGA (0– 3) <0.5, and prednisone ≤5 mg/day. LLDAS required SLEDAI- 2K ≤4, PhGA (0– 3) ≤1, and prednisone ≤7.5 mg/day. HRQoL was measured with the SF- 36 physical and mental component summary (PCS and MCS), and EQ- 5D- 3L. Minimal clinically important difference (MCID) at week 52 for PCS and MCS was set to 2.5, and for EQ- 5D- 3L utility index to 0.040. Associations were assessed using quantile regression analysis. Adjustments for demographics, disease duration, organ damage and baseline status were incorporated.Results: The minimum cumulative attainment of remission to achieve a benefit in PCS ≥MCID at week 52 was four visits (corresponding to 16 weeks) (β=0.63), while 7 visits (28 weeks) were required for MCS differences ≥MCID (β=0.37). Correspondingly, 9 visits in LLDAS (36 weeks) were required for achieving differences ≥MCID in both PCS (b=0.28) and MCS (β=0.29). Table 1 shows 95% confidence intervals and p values. When analysing the impact of sustained remission and LLDAS, four consecutive visits in remission (16 weeks) were required for PCS ≥MCID (b=0.70), whereas six visits (24 weeks) were required for MCS ≥MCID (b=0.46). Sustained LLDAS for nine consecutive visits (36 weeks) was needed for PCS and MCS ≥MCID (b=0.31 and 0.31, respectively). For EQ- 5D ≥MCID to be reached, a cumulative total of seven visits (28 weeks) in remission (b=0.006), or eight visits (32 weeks) in LLDAS (b=0.005) was required, whereas if sustained, remission for six visits (24 weeks; b=0.008) or LLDAS for seven visits (28 weeks; b=0.006) were sufficient.Conclusion: Attainment of remission or LLDAS in the BLISS- 52 and BLISS- 76 trials of belimumab was associated with improved HRQoL. Less time was required in remission than in LLDAS to achieve clinically important differences in multiple HRQoL aspects. Clinically important differences in HRQoL required shorter total time if the remission or LLDAS was sustained. Clinically important differences in mental aspects of HRQoL required longer time in remission than physical aspects. The impact of cumulative and sustained remission or LLDAS on HRQoL adds evidence on the clinical importance of these treat- to- target endpoints.References:1) van Vollenhoven R. et al. Ann Rheum Dis. 20172) Franklyn K. et al. Ann Rheum Dis. 2016
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18.
  • Gomez, Alvaro, et al. (författare)
  • Belimumab and antimalarials combined against renal flares in patients treated for extra-renal systemic lupus erythematosus : results from 4 phase III clinical trials
  • 2024
  • Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 63:2, s. 338-348
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To determine the effect of antimalarial agents (AMA) and different doses and pharmaceutical forms of belimumab on preventing renal flares in patients with systemic lupus erythematosus (SLE) treated for extra-renal disease.METHODS: We pooled data from the BLISS-52, BLISS-76, BLISS-SC and BLISS-Northeast Asia trials of belimumab (N = 3225), that included patients with active SLE yet no severe ongoing nephritis. Participants were allocated to receive intravenous belimumab 1 mg/kg, intravenous belimumab 10 mg/kg, subcutaneous belimumab 200 mg, or placebo in addition to standard therapy. We estimated hazards of renal flare development throughout the study follow-up (52-76 weeks) using Cox regression analysis.RESULTS: In total, 192 patients developed a renal flare after a median of 197 days. Compared with placebo, the risk of renal flares was lower among patients receiving intravenous belimumab 10 mg/kg (HR: 0.62; 95% CI: 0.41-0.92; p = 0.018) and intravenous belimumab 1 mg/kg (HR: 0.42; 95% CI: 0.22-0.79; p = 0.007), while no significant association was found for subcutaneous belimumab 200 mg. AMA use yielded a lower hazard of renal flares (HR: 0.66; 95% CI: 0.55-0.78; p < 0.001). The protection conferred was enhanced when belimumab and AMA were co-administered; the lowest flare rate was observed for the combination intravenous belimumab 1 mg/kg and AMA (18.5 cases per 1000 person-years).CONCLUSIONS: The protection conferred from belimumab against renal flare development in patients treated for extra-renal SLE appears enhanced when belimumab is administered along with AMA. The prominent effect of low-dose belimumab warrants investigation of the efficacy of intermediate doses.
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19.
  • Gomez, Alvaro, et al. (författare)
  • Do biological agents improve health-related quality of life in patients with systemic lupus erythematosus? Results from a systematic search of the literature
  • 2022
  • Ingår i: Autoimmunity Reviews. - : Elsevier. - 1568-9972 .- 1873-0183. ; 21:11
  • Forskningsöversikt (refereegranskat)abstract
    • Despite an unprecedented rise in the number of biological therapies developed for systemic lupus erythematosus (SLE) during the last decades, most randomised clinical trials (RCTs) have failed to reach their primary efficacy endpoint. These endpoints mainly constitute composite outcomes that encompass disease activity indices derived from clinician-reported and laboratory data and do not necessarily reflect the patient perspective, as symptoms that represent major concerns to patients, such as fatigue, are seldom part of the evaluation. To overcome this limitation, patient-reported outcomes (PROs) constitute useful tools for evaluating the effect of an intervention on facets that are particularly relevant for the patients. In the present review, we performed a systematic literature search aiming to examine the effect of biological therapies on SLE patients' health-related quality of life (HRQoL) and fatigue in RCT and real-life settings. We summarised results concerning 14 different biological agents, the majority of which targeting B cells or type I interferons, and discuss strategies that have been used to analyse HRQoL data, putting emphasis on minimal clinically important differences and the potential use of PROs as distinct targets in treat-to-target approaches. Lastly, we discuss differences between generic and disease-specific PRO measures and highlight the need of using a combination thereof aiming to capture the patient perspective in a comprehensive manner.
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20.
  • Gomez, Alvaro, et al. (författare)
  • Impact of Belimumab on Patient-Reported Outcomes in Systemic Lupus Erythematosus : Insights from Clinical Trials and Real-World Evidence
  • 2023
  • Ingår i: Patient Related Outcome Measures. - : Dove Medical Press Ltd.. - 1179-271X. ; 14, s. 1-13
  • Forskningsöversikt (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease, characterised by a relapsing-remitting pattern of inflammatory activity, with each relapse contributing to irreversible end-organ damage with detrimental effects on patients' course, adding up to morbidity burden and shortening life-length. Along with several other demographic, socioeconomic, and life-style factors, high inflammatory activity and accrued organ damage have been coupled with adverse health-related quality of life (HRQoL) within physical, mental, and psychosocial aspects. The management of SLE has improved substantially during the last decades, owing to a technological explosion that has advanced drug development towards more targeted options. Being the first drug to be approved for SLE in more than half a century and the first in history biological agent for SLE, the introduction in 2011 of the monoclonal antibody belimumab that specifically binds to the soluble counterpart of B cell activating factor (BAFF) was a breakthrough in SLE drug development. The efficacy and favourable safety profile of belimumab has been demonstrated across several clinical trials and observational studies. Herein, we reviewed the literature and provide a summary on the effects of belimumab on SLE patients' HRQoL based on 23 studies. Belimumab has been shown to induce clinically important improvements in physical aspects of HRQoL and in fatigue, the latter being a common and major complaint within the SLE population. People with SLE overall benefit more from belimumab within physical compared with mental aspects of HRQoL. However, despite improvements of clinical and immunological features upon therapy with belimumab, HRQoL perception remains unsatisfactory for a substantial percentage of the patients. Finally, our review made apparent an urgent need for optimisation of the use of patient-reported outcome measures, both in research and clinical practice.
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21.
  • Gomez, Alvaro, et al. (författare)
  • Obesity and tobacco smoking are independently associated with poor patient-reported outcomes in SLE : a cross-sectional study
  • 2024
  • Ingår i: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 44:5, s. 851-861
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated associations of obesity and tobacco smoking with health-related quality of life (HRQoL), pain, fatigue, and functional impairment in systemic lupus erythematosus (SLE). Furthermore, we explored whether there was an effect modification between these two factors. We included adult SLE patients from the Linköping University Hospital (n = 325) in the present cross-sectional analysis. We further included population-based controls and performed cardinality matching to balance age and sex distributions with cases (n = 224). HRQoL was assessed with the EQ-5D index score; pain, fatigue, and overall SLE-related health state with visual analogue scales (VAS; 0 [best] to 100 [worst]); and functional impairment with the HAQ-DI. Unacceptable outcomes were defined as VAS scores corresponding to the 90th percentile derived from the matched controls. SLE patients reported worse scores than controls in all measures, and approximately 30% experienced unacceptable outcomes. When compared with normal-weight, obese SLE patients reported lower HRQoL, and greater functional impairment and risk of unacceptable pain (OR: 3.2; 95% CI 1.6-6.7) and fatigue (OR: 2.1; 95% CI 1.0-4.3). Similarly, the current smokers reported higher levels of functional impairment and a greater risk of unacceptable pain (OR: 3.8; 95% CI 1.8-8.2) and fatigue (OR: 2.8; 95% CI 1.3-5.9) than never smokers. The associations were independent of age, sex, disease duration, disease activity, and organ damage. There was no evidence of a synergistic effect between increased BMI and smoking on any outcome. In summary, obesity and smoking are risk factors for unacceptable patient-reported outcomes in SLE, regardless of clinical activity.
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22.
  • Gómez-Correa, Luisa F., et al. (författare)
  • Canopy tree mortality depends on the proportion of crown exposed to sunlight, but this effect varies with species' wood density
  • 2023
  • Ingår i: Biotropica. - 0006-3606 .- 1744-7429. ; 55, s. 1136-1147
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding what drives changes in tree mortality as well as the covariates influencing trees' response is a research priority to predict forest responses to global change. Here, we combined drone photogrammetry and ground-based data to assess the influence of crown exposure to light (relative to total crown area), growth deviations (relative to conspecifics), tree size, and species' wood density (as a surrogate for light-demanding and shade-tolerant life-history strategies) on the mortality of 984 canopy trees in an Amazon terra firme forest. Trees with lower wood density were less prone to die when their proportion of crown was more exposed to sunlight, but this relationship with relative crown exposure weakened and slightly reversed as wood density increased. Trees growing less than their species average had higher mortality, especially when the species' wood density decreased. The role of wood density in determining the survival of canopy trees under varying light conditions indicates differential responses of light-demanding versus shade-tolerant species. Our results highlight the importance of accounting for life-history strategies, via plant functional types, in vegetation dynamic models aiming to predict forest demography under a rapidly changing climate. Abstract in Spanish is available with online material.
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23.
  • Hua, Nicole, et al. (författare)
  • Sensitivity analysis of EQ-5D-3L index scores in terms of discriminative and known-groups validity in SLE : introducing Adequate Health State
  • 2023
  • Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:12, s. 3916-3923
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate the ability of different EQ-5D-3L index scores to discriminate between verum drug and placebo (discriminant validity) as well as between responders and non-responders (known-groups validity) in the SLE patient population of two phase III clinical trials of belimumab.METHODS: Data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (N = 1684), which both showed superiority of belimumab to placebo, were utilised. Responders were defined as SLE Responder Index 4 (SRI-4) achievers at week 52. The Pearson's χ2 and Mann-Whitney U tests were used for comparisons, and logistic regression analysis was used for adjustments for confounders and assessment of independence.RESULTS: While full health state (FHS; EQ-5D index score 1) showed the best ability to discriminate between belimumab and placebo (adjusted OR: 1.47; 95% CI: 1.11-1.96; P = 0.008) and between SRI-4 responders and non-responders (adjusted OR: 3.47; 95% CI: 1.29-10.98; P = 0.020), the discriminative ability of EQ-5D index scores 0.800 or more reached statistical significance for both discriminant validity (adjusted OR: 1.29; 95% CI: 1.02-1.63; P = 0.036) and known-groups validity (adjusted OR: 3.08; 95% CI: 1.16-9.69; P = 0.034).CONCLUSION: Overall, higher EQ-5D index scores were associated with increasing ability to discriminate between belimumab and placebo, and between responders and non-responders. EQ-5D index scores less stringent than FHS may be clinically relevant HRQoL goals of treatment in patients with SLE, introducing the concept of EQ-5D adequate health state when FHS is not achievable.
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24.
  • Iani, Edoardo, et al. (författare)
  • MIDIS : JWST NIRCam and MIRI Unveil the Stellar Population Properties of Lyα Emitters and Lyman-break Galaxies at z ≃ 3–7
  • 2024
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 963:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We study the stellar population properties of 182 spectroscopically confirmed (MUSE/VLT) Lyα emitters (LAEs) and 450 photometrically selected Lyman-break galaxies (LBGs) at z = 2.8–6.7 in the Hubble Extreme Deep Field. Leveraging the combined power of Hubble Space Telescope and JWST NIRCam and MIRI observations, we analyze their rest-frame UV-through-near-IR spectral energy distributions, with MIRI playing a crucial role in robustly assessing the LAEs' stellar masses and ages. Our LAEs are low-mass objects (log10(M⋆/M⊙)≃7.5) with little or no dust extinction (E(B − V) ≃ 0.1) and a blue UV continuum slope (β ≃ −2.2). While 75% of our LAEs are young (<100 Myr), the remaining 25% have significantly older stellar populations (≥100 Myr). These old LAEs are statistically more massive, less extinct, and have lower specific star formation rate than young LAEs. Besides, they populate the plane of M⋆ versus star formation rate along the main sequence of star-forming galaxies, while young LAEs populate the starburst region. The comparison between the LAEs' properties and those of a stellar-mass-matched sample of LBGs shows no statistical difference between these objects, except for the LBGs' redder UV continuum slope and marginally larger E(B − V) values. Interestingly, 48% of the LBGs have ages <10 Myr and are classified as starbursts, but lack detectable Lyα emission. This is likely due to H i resonant scattering and/or dust-selective extinction. Overall, we find that JWST observations are crucial in determining the properties of LAEs and shedding light on their comparison with LBGs.
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25.
  • Jägerback, Sandra, et al. (författare)
  • Predictors of renal flares in systemic lupus erythematosus : a post-hoc analysis of four phase III clinical trials of belimumab
  • 2024
  • Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332.
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To identify predictors of renal flares in patients with SLE treated for active extra-renal disease.METHODS: Data from four clinical trials of belimumab in SLE (BLISS-52, NCT00424476; BLISS-76, NCT00410384; BLISS-NEA, NCT01345253; BLISS-SC, NCT01484496) were used. Patients were assigned to belimumab or placebo on top of standard therapy. We investigated the performance of predictors of renal flares through 52-76 weeks using proportional hazards regression analysis.RESULTS: Of 3225 participants, 192 developed at least one renal flare during follow-up, with the first occurring after a median time of 197 days. Current/former renal involvement (HR: 15.4; 95% CI: 8.3-28.2; p< 0.001), low serum albumin levels (HR 0.9; 95% CI: 0.8-0.9; p< 0.001), proteinuria (HR: 1.6; 95% CI: 1.5-1.7; p< 0.001), and low C3 levels (HR: 2.9; 95% CI: 2.1-4.1; p< 0.001) at baseline appeared robust determinants of renal flares. Anti-dsDNA positivity yielded an increased hazard for renal flares (HR: 2.1; 95% CI: 1.4-3.2; p< 0.001), which attenuated after adjustments. Anti-Sm positivity was associated with renal flares in the placebo (HR: 3.7; 95% CI: 2.0-6.9; p< 0.001) but not in the belimumab subgroup, whereas anti-ribosomal P positivity was associated with renal flares in the belimumab subgroup only (HR: 2.8; 95% CI: 1.5-5.0; p= 0.001).CONCLUSION: A history of renal involvement, high baseline proteinuria, hypoalbuminaemia, and C3 consumption were robust determinants of impending renal flares. Beyond anti-dsDNA, anti-Sm and anti-ribosomal P protein antibody positivity may have value in surveillance of renal SLE.
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26.
  • Lawrenson, Kate, et al. (författare)
  • Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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27.
  • Lindblom, Julius, et al. (författare)
  • EQ-5D full health state after therapy heralds reduced hazard to accrue subsequent organ damage in systemic lupus erythematosus
  • 2022
  • Ingår i: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate whether self-reported EQ-5D full health state (FHS) after therapeutic intervention for active systemic lupus erythematosus (SLE) is associated with a reduced risk to accrue organ damage. In a separate analysis, we sought to investigate associations between experience of "no problems" in each one of the five dimensions of EQ-5D and the risk to accrue damage.METHODS: Data from the open-label extension periods of the BLISS-52 and BLISS-76 trials of belimumab in SLE (NCT00724867; NCT00712933) were used (N = 973). FHS was defined as an experience of "no problems" in all five EQ-5D dimensions. Organ damage was assessed annually using the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Associations between the three-level version of the EQ-5D (EQ-5D-3L) responses at open-label baseline and the first documented increase in organ damage were investigated using Cox regression accounting for age, sex, ancestry, SDI at baseline, and background therapy, and associations with SDI items were investigated using phi (φ) correlation analyses.RESULTS: A total of 147 patients (15.1%) accrued organ damage during follow-up, with the first increase in their SDI score occurring after a mean time of 29.1 ± 19.6 months. Lower proportions of FHS respondents accrued damage over a course of up to 7.9 years of open-label follow-up compared with no FHS respondents (p = 0.004; derived from the logrank test). FHS was associated with a reduced hazard to accrue subsequent organ damage (HR: 0.60; 95% CI: 0.38-0.96; p = 0.033) after adjustments, as was experience of "no problems" in mobility (HR: 0.61; 95% CI: 0.43-0.87; p = 0.006). "No problems" in mobility was negatively correlated with musculoskeletal damage accrual (φ = -0.08; p = 0.008) and associated with a lower hazard to accrue musculoskeletal damage in Cox regression analysis (HR: 0.38; 95% CI: 0.19-0.76; p = 0.006).CONCLUSION: Experience of EQ-5D-3L FHS and "no problems" in mobility after therapeutic intervention heralded reduced hazard to accrue subsequent organ damage, especially musculoskeletal damage, suggesting that optimisation of these health-related quality of life aspects constitutes a clinically relevant treatment target in patients with SLE, along with clinical and laboratory parameters.
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28.
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29.
  • Maxwell, Christopher A., et al. (författare)
  • Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
  • 2011
  • Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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30.
  • Meyer, H.F., et al. (författare)
  • Overview of physics studies on ASDEX Upgrade
  • 2019
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
  • Forskningsöversikt (refereegranskat)abstract
    • The ASDEX Upgrade (AUG) programme, jointly run with the EUROfusion MST1 task force, continues to significantly enhance the physics base of ITER and DEMO. Here, the full tungsten wall is a key asset for extrapolating to future devices. The high overall heating power, flexible heating mix and comprehensive diagnostic set allows studies ranging from mimicking the scrape-off-layer and divertor conditions of ITER and DEMO at high density to fully non-inductive operation (q 95 = 5.5, ) at low density. Higher installed electron cyclotron resonance heating power 6 MW, new diagnostics and improved analysis techniques have further enhanced the capabilities of AUG. Stable high-density H-modes with MW m-1 with fully detached strike-points have been demonstrated. The ballooning instability close to the separatrix has been identified as a potential cause leading to the H-mode density limit and is also found to play an important role for the access to small edge-localized modes (ELMs). Density limit disruptions have been successfully avoided using a path-oriented approach to disruption handling and progress has been made in understanding the dissipation and avoidance of runaway electron beams. ELM suppression with resonant magnetic perturbations is now routinely achieved reaching transiently . This gives new insight into the field penetration physics, in particular with respect to plasma flows. Modelling agrees well with plasma response measurements and a helically localised ballooning structure observed prior to the ELM is evidence for the changed edge stability due to the magnetic perturbations. The impact of 3D perturbations on heat load patterns and fast-ion losses have been further elaborated. Progress has also been made in understanding the ELM cycle itself. Here, new fast measurements of and E r allow for inter ELM transport analysis confirming that E r is dominated by the diamagnetic term even for fast timescales. New analysis techniques allow detailed comparison of the ELM crash and are in good agreement with nonlinear MHD modelling. The observation of accelerated ions during the ELM crash can be seen as evidence for the reconnection during the ELM. As type-I ELMs (even mitigated) are likely not a viable operational regime in DEMO studies of 'natural' no ELM regimes have been extended. Stable I-modes up to have been characterised using -feedback. Core physics has been advanced by more detailed characterisation of the turbulence with new measurements such as the eddy tilt angle - measured for the first time - or the cross-phase angle of and fluctuations. These new data put strong constraints on gyro-kinetic turbulence modelling. In addition, carefully executed studies in different main species (H, D and He) and with different heating mixes highlight the importance of the collisional energy exchange for interpreting energy confinement. A new regime with a hollow profile now gives access to regimes mimicking aspects of burning plasma conditions and lead to nonlinear interactions of energetic particle modes despite the sub-Alfvénic beam energy. This will help to validate the fast-ion codes for predicting ITER and DEMO.
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31.
  • Nakamura, Lukas (författare)
  • Small energy isotopies of loose Legendrian submanifolds
  • 2023
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In the first paper, we prove that for a closed Legendrian submanifold L of dimension n>2 with a loose chart of size η, any Legendrian isotopy starting at L can be C0-approximated by a Legendrian isotopy with energy arbitrarily close to η/2. This in particular implies that the displacement energy of loose displaceable Legendrians is bounded by half the size of its smallest loose chart, which proves a conjecture of Dimitroglou Rizell and Sullivan.In the second paper, we show that the Legendrian lift of an exact, displaceable Lagrangian has vanishing Shelukhin-Chekanov-Hofer pseudo-metric by lifting an argument due to Sikorav to the contactization. In particular, this proves the existence of such Legendrians, providing counterexamples to a conjecture of Rosen and Zhang. After completion of the manuscript, we noticed that Cant (arXiv:2301.06205) independently proved a more general version of our main result.
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32.
  • Parodis, Ioannis, 1981-, et al. (författare)
  • Associations Between Early Changes in Circulating B Cell Subsets and Severe Flare in Systemic Lupus Erythematosus : Results from Three Phase III Trials of Belimumab
  • 2021
  • Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 73:Suppl. 9, s. 2699-2700
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background/Purpose: Belimumab is the only approved targeted treatment for systemic lupus erythematosus (SLE). Identification of early predictors of response or non- response to therapy is imperative to optimize surveillance and decision- making. We studied early changes in B cell subsets in relation to flare during standard therapy plus belimumab or placebo given to patients with active SLE within the frame of three phase III clinical trials of belimumab.Methods: We analyzed pooled 52- week data from BLISS- 76 (N=819), BLISS- SC (N=836), and BLISS North- East Asia (N=60). B cell subsets were determined with flow cytometry. Severe flare was evaluated according to the SELENA-SLEDAI Flare Index every fourth week. We investigated B cell changes relative to baseline using proportional hazards regression analysis.Results: Early decreases in CD19+CD20- CD138+ long- lived (HR: 0.7; 95% CI: 0.56– 0.98; P=0.034) and CD19+CD-38brightCD27bright SLE- associated plasma cells (HR: 0.7; 95% CI: 0.50– 0.87; P=0.003) from baseline through week 24 were negatively associated with the development of a severe flare during the study period, i.e. through week 52 from treatment initiation. A similar trend was seen for decreases in naïve CD19+CD20+CD27-  B cells (HR: 0.7; 95% CI: 0.56– 1.00; P=0.051). No such association was observed for early changes in the total CD19+CD20+ B cell pool, or in CD19+CD20+CD27+ memory B cells, CD19+CD20+CD69+ activated B cells, CD19+CD20+CD138+ cells or CD19+CD20- CD27bright short- lived plasma cells. The association with CD19+CD38brightCD27bright SLE- associated plasma cells held true for patients treated with belimumab (any dose) (HR: 0.7; 95% CI: 0.47– 0.97; P=0.032) but not placebo, while placebo receivers showing reductions in CD19+CD20- CD138+ long- lived plasma cells displayed a lower probability to flare (HR: 0.6; 95% CI: 0.38– 0.87; P=0.009).Conclusion: Early decreases in long- lived circulating plasma cells were negatively associated with severe flares in patients with active SLE treated with standard immunosuppression with or without add- on belimumab, while reductions in circulating CD19+CD38brightCD27bright SLE- associated plasma cells may prove a useful early biological marker of favorable response to belimumab therapy.
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33.
  • Parodis, Ioannis, et al. (författare)
  • Autoantibody and cytokine profiles during treatment with belimumab in patients with systemic lupus erythematosus
  • 2020
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated whether belimumab treatment impacts on levels of autoantibodies and cytokines of interest in systemic lupus erythematosus (SLE). Longitudinally collected serum samples from 78 belimumab-treated Swedish SLE patients were analysed. Serum cytokine levels were determined using Luminex xMAP technology, and nuclear antigen autoantibody specificities using addressable laser bead immunoassay. In patients with detectable levels at baseline, interferon (IFN)-α2 levels were lower at month 6 (median; interquartile range (IQR): 8.9; 1.5–54.9 pg/mL) versus baseline (28.4; 20.9–100.3 pg/mL; p = 0.043). Interleukin (IL)-6 (baseline: 7.1; 2.9–16.1 pg/mL) decreased from month 6 (0.5; 0.5–6.3 pg/mL; p = 0.018) and throughout a 24 month follow-up. IL-10 (baseline: 12.6; 2.8–29.7 pg/mL) showed more rapid decreases from month 3 (1.8; 0.6–9.1 pg/mL; p = 0.003). Levels of anti-dsDNA (p < 0.001), anti-Smith antigen (Sm) (p = 0.002), anti-U1 small nuclear ribonucleoprotein (U1RNP) (p < 0.001), anti-Sm-U1RNP complex (p = 0.028), and anti-ribosomal P (p = 0.012) antibodies decreased from month 3 and remained decreased. Anti-Sm positivity at baseline was associated with higher probability and/or shorter time to achieve sustained SLE responder index-4 response (hazard ratio (HR): 2.52; 95% CI: 1.20–5.29; p = 0.015), independently of other factors. Decline of IL-6 levels through month 3 was greater in responders. In summary, belimumab treatment lowered IFN-α2, IL-6, and IL-10 levels, as well as levels of multiple autoantibodies, however after different time spans. Notably, anti-Sm positivity and early decline in IL-6 levels were associated with favorable treatment outcome.
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34.
  • Parodis, Ioannis, 1981-, et al. (författare)
  • B Cell Kinetics upon Therapy Commencement for Active Extrarenal Systemic Lupus Erythematosus in Relation to Development of Renal Flares : Results from Three Phase III Clinical Trials of Belimumab
  • 2022
  • Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:22
  • Tidskriftsartikel (refereegranskat)abstract
    • Renal flares constitute major determinants of poor prognosis in people living with systemic lupus erythematosus (SLE). The aim of the present study was to investigate changes in B cell subsets in relation to renal flares upon initiation of standard therapy (ST) plus belimumab or placebo in patients with SLE. Using data from the BLISS-76, BLISS-SC, and BLISS Northeast Asia trials, we investigated associations of relative to baseline rapid (through week 8) and early (through week 24) percentage changes in circulating CD19+ B cell subsets characterised through flow cytometry, anti-dsDNA antibodies, and complement levels with the occurrence of renal flares over one year. Patients who developed renal flares showed more prominent rapid decreases in CD19+CD20+CD138+ short-lived plasma cells (-50.4% vs. -16.7%; p = 0.019) and CD19+CD20-CD27bright plasmablasts (-50.0% vs. -29.9%; p = 0.020) compared to non-flaring patients, followed by a subsequent return. Less prominent rapid reductions in CD19+CD27-CD24brightCD38bright transitional B cells (-42.9% vs. -75.0%; p = 0.038) and CD19+CD20-CD138+ peripheral long-lived plasma cells (-11.3% vs. -29.2%; p = 0.019) were seen in belimumab-treated-but not placebo-treated-patients who developed renal flares compared to belimumab-treated patients who did not. Rapid and early changes in anti-dsDNA or complement levels showed no clear association with renal flares. In summary, a rapid drop followed by a subsequent return in circulating short-lived plasma cells and plasmablasts upon treatment for active extra-renal SLE portended renal flares, indicating a need for therapeutic adjustments in patients showing such B cell patterns. Rapid decreases in transitional B cells and peripheral long-lived plasma cells upon belimumab therapy commencement may signify a greater protection against renal flares. B cell kinetics may prove useful in early drug evaluation.
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35.
  • Parodis, Ioannis, 1981-, et al. (författare)
  • Early B Cell and Plasma Cell Kinetics Upon Treatment Initiation Portend Flares in Systemic Lupus Erythematosus : A Post-Hoc Analysis of Three Phase III Clinical Trials of Belimumab
  • 2022
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate changes in B cell subsets in relation to disease flares upon initiation of standard therapy (ST) plus belimumab or placebo in patients with systemic lupus erythematosus (SLE).Patients and Methods: Using data from the BLISS-76, BLISS-SC and BLISS Northeast Asia trials, we investigated associations of relative to baseline rapid (through week 8) and early (through week 24) changes in peripheral B cell subsets, anti-dsDNA and complement levels with the occurrence of disease flares from week 24 through week 52 (Mann-Whitney U tests) or the entire study follow-up (Cox regression analysis), assessed using the SELENA-SLEDAI Flare Index.Results: Patients on ST alone who flared displayed less prominent early decreases in CD19+CD20-CD138+ long-lived plasma cells (-16.1% versus -35.1%; P=0.012). In all arms combined, patients who developed severe flares showed less prominent early decreases in CD19+CD20-CD138+ long-lived plasma cells (-23.5% versus -39.4%; P=0.028) and CD19+CD27brightCD38bright SLE-associated plasma cells (-19.0% versus -27.8%; P=0.045). After adjustment for rapid changes, early increases in overall CD19+CD20+ B cells (HR: 1.81; 95% CI: 1.08-3.05; P=0.024) and early increases or no return after a rapid expansion in CD19+CD20+CD27+ memory B cells (HR: 1.58; 95% CI: 1.18-2.11; P=0.002) portended subsequent severe flares. Patients who developed flares of any severity showed no or less prominent rapid (0.0% versus -12.5%; P<0.001) or early (-1.9% versus -21.7%; P<0.001) decreases in anti-dsDNA levels, and patients who developed severe flares showed no or less prominent early decreases in anti-dsDNA levels (0.0% versus -13.3%; P=0.020). Changes in complement levels exhibited no ability to distinguish flaring from non-flaring patients.Conclusions: Increase or lack of decrease in certain circulating B cell subsets or anti-dsDNA levels upon treatment initiation for active SLE heralded subsequent severe disease flares. A rapid expansion of memory B cells may signify sustained response to therapy when followed by a subsequent drop, while no return or delayed increases in memory B cells may portend flaring. Peripheral B cell and serological marker kinetics may help identify patients in whom therapeutic modifications could protect against flare development, and may hence prove a useful complement to traditional surveillance and early treatment evaluation in SLE.
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36.
  • Parodis, Ioannis, 1981-, et al. (författare)
  • Early Changes in B and Plasma Cell Subsets and Traditional Serological Markers as Predictors of SRI-4 Response to Therapy in Systemic Lupus Erythematosus
  • 2022
  • Ingår i: Frontiers in medicine. - : Frontiers Media S.A.. - 2296-858X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: With the premise of the hypothesis that early biological responses to therapy for active systemic lupus erythematosus (SLE) portend later clinical improvements, we studied changes in B cell subsets and traditional serological markers in relation to clinical response to standard therapy (ST) with or without the addition of belimumab.Patients and Methods: We analyzed data from the BLISS-76, BLISS-SC, and BLISS Northeast Asia trials (N = 1712). Circulating CD19+ B cell subsets were determined by flow-cytometry. We studied associations of relative to baseline percentage changes in circulating B and plasma cell subsets, anti-dsDNA antibody levels and complement levels with SLE Responder Index (SRI)-4 response after 52 weeks of treatment. Changes occurring through week 8 were deemed "rapid," through week 24 "early," and thereafter "delayed".Results: In the analysis of the entire cohort, SRI-4 responders showed more prominent decreases from baseline through week 52 in CD19+CD20+CD27- naïve B cells (median change: -61.2% versus -50.0%; P = 0.004), CD19+CD20-CD27 bright plasmablasts (-44.9% versus -33.3%; P = 0.011), and CD19+CD20-CD138+ long-lived plasma cells (-48.2% versus -37.1%; P = 0.024), and a more prominent rapid (+92.0% versus +66.7%; P = 0.002) and early (+60.0% versus +49.5%; P = 0.033) expansion of CD19+CD20+CD27+ memory B cells than non-responders. More prominent rapid reductions in anti-dsDNA (-14.8% versus -8.7%; P = 0.043) and increases in C3 (+4.9% versus +2.1%; P = 0.014) and C4 levels (+11.5% versus +8.3%; P = 0.017) were documented in SRI-4 responders compared with non-responders among patients who received add-on belimumab, but not among patients who received non-biological ST alone.Conclusion: SRI-4 responders showed a more prominent rapid expansion of memory B cells and more prominent delayed reductions in naïve B cells, plasmablasts and long-lived plasma cells. Moreover, clinical response to belimumab was associated with preceding more prominent reductions of anti-dsDNA and increases in C3 and C4 levels. Monitoring biological changes may prove useful in SLE patient surveillance and early treatment evaluation.
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37.
  • Parodis, Ioannis, 1981-, et al. (författare)
  • Early Increase in Circulating Memory B Cells Portends Clinical Response to Treatment in Pooled Data from Three Phase III Trials of Belimumab
  • 2021
  • Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 73:Suppl. 9, s. 2695-2696
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background/Purpose: Belimumab blocks soluble B cell activating factor (BAFF) and is the only to date approved targeted treatment for systemic lupus erythematosus (SLE). Identification of biological predictors of response occurring earlier upon treatment would provide measurable tools to improve patient monitoring and stratification according to likelihood of response. We investigated early changes in B lymphocyte subsets in relation to response to standard therapy plus belimumab or placebo given to patients with active SLE and mainly musculoskeletal and mucocutaneous symptoms.Methods: We analyzed pooled data from belimumab phase III clinical trials including BLISS-76 (N=819) and BLISS-SC (N=836); in addition, 60 patients from the BLISS North- East Asia trial were included in the analysis. B lymphocyte subsets were determined with flow cytometry. Treatment response was assessed using the composite measure SLE Responder Index 4 (SRI- 4), defined as decrease in SLEDAI by ≥4 points, no worsening in the physician’s global assessment by >30% and no new British Lupus Isles Assessment Group (BILAG) index (≥1 A or ≥2 B), at week 52. Additionally, persistence of SRI- 4 through week 52 was evaluated. We investigated B cell changes relative to baseline using logistic or proportional hazards regression analysis, as appropriate.Results: We found an association between an early expansion of CD19+CD20+CD27+ memory B cells from baseline through week 8 and attainment of SRI- 4 response at week 52 (OR: 1.5; 95% CI: 1.18– 1.89; P=0.001), or for relative increases >10% (OR: 1.5; 95% CI: 1.17– 1.83; P=0.001). Expansion above this threshold of 10% was also associated with increased probability or shorter time to achieve SRI- 4 response that was maintained through week 52 (HR: 1.4; 95% CI: 1.15– 1.61; P< 0.001). Notably, belimumab treatment (any dose) yielded an 11.5- fold increased probability of memory B cell expansion through week 8 compared with placebo (95% CI: 8.74– 15.02; P< 0.001). No association with SRI- 4 response was observed for early changes in CD19+CD20+ B cells, CD19+CD20+CD27-  naïve B cells, CD19+CD20+CD69+ activated B cells, CD19+CD20- CD27bright short- lived plasma cells, CD19+CD20- CD138+ long- lived plasma cells, or CD19+CD38brightCD27bright SLE- associated plasma cells.Conclusion: Early increases in memory B cells through the first 8 weeks of therapy, mainly driven by belimumab, portended good and sustained clinical response within one year from treatment initiation. Early immunological changes preceding the clinical outcome and may prove useful in early evaluation of belimumab therapy.
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38.
  • Parodis, Ioannis, 1981-, et al. (författare)
  • Lifestyle interventions in the management of systemic sclerosis : a systematic review of the literature
  • 2024
  • Ingår i: Rheumatology. - : Oxford University Press. - 2514-1775. ; 8:2
  • Forskningsöversikt (refereegranskat)abstract
    • OBJECTIVES: We aimed to investigate the efficacy of lifestyle interventions for the management of SSc. METHODS: We searched the MEDLINE, Embase, Web of Science and CINAHL databases in June 2021. We included studies conducted on five or more patients with SSc published between 1 January 2000 and the search date evaluating lifestyle interventions, excluding systematic reviews without meta-analyses. Critical appraisal was conducted using critical appraisal tools from the Joanna Briggs Institute. Thirty-six studies were included for full-text evaluation.RESULTS: A total of 17 studies evaluated the effect of physical exercise alone, whereas 14 studies evaluated educational interventions for mental health management, often with physical exercise as a central component. At an aggregated level, these studies support patient education and physical exercise for the improvement of physical function, in particular hand and mouth function. Studies on diet and nutrition were few (n = 5) and pertained to gastrointestinal as well as anthropometric outcomes; these studies were insufficient to support any conclusions.CONCLUSION: Physical exercise and patient education should be considered for improving physical function in patients with SSc. These interventions can be provided alongside pharmacotherapy, but there is no evidence supporting that they can be a substitute. Further research should aim at assessing the effects of reductions of harmful exposures, including tobacco smoking and alcohol, improving sleep and enhancing social relations, three hitherto underexplored facets of lifestyle in the context of SSc.
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39.
  • Parodis, Ioannis, et al. (författare)
  • Smoking reduces the efficacy of belimumab in mucocutaneous lupus.
  • 2018
  • Ingår i: Expert Opinion on Biological Therapy. - : Informa Healthcare. - 1471-2598 .- 1744-7682. ; 18:8, s. 911-920
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Recently, we demonstrated a negative impact of smoking on belimumab efficacy in patients with systemic lupus erythematosus (SLE). Here, we particularly investigated clinical effects of belimumab and a potential impact of smoking in mucocutaneous and articular SLE.METHODS: We surveyed 62 SLE patients treated between 2011 and 2017. Evaluation included the mucocutaneous descriptors of SLEDAI-2K (rash, alopecia, mucosal ulcers; mcSLEDAI-2K), CLASI, the arthritis SLEDAI-2K descriptor (arSLEDAI-2K) and the 28-joint count.RESULTS: mcSLEDAI-2K and CLASI activity decreased from baseline to month 6 and 12 (P<0.001 for all). No worsening in CLASI damage was observed. Current or previous smokers displayed a higher probability of unchanged/worsened mcSLEDAI-2K compared to never smokers (OR: 6.4; 95% CI: 1.5-27.4; P=0.012), also after adjustment for antimalarial agents. arSLEDAI-2K scores had decreased at month 6 (P<0.001) and 12 (P<0.001). Likewise, tender and swollen 28-joint counts had improved at month 6 (P=0.010 and P<0.001, respectively) and 12 (P=0.001 for both). We observed no impact of smoking on belimumab efficacy in articular SLE.CONCLUSION: We observed a negative impact of smoking on the efficacy of belimumab in mucocutaneous SLE. In contrast, no impact of smoking on belimumab efficacy was seen in patients with articular manifestations.
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40.
  • Parodis, Ioannis, 1981-, et al. (författare)
  • Systematic literature review informing the EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis
  • 2023
  • Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 9:3
  • Forskningsöversikt (refereegranskat)abstract
    • Through this systematic literature review, we assembled evidence to inform the EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). We screened articles published between January 2000 and June 2021. Studies selected for data extraction (118 for SLE and 92 for SSc) were thematically categorised by the character of their intervention. Of 208 articles included, 51 were classified as robust in critical appraisal. Physical activity was the most studied management strategy and was found to be efficacious in both diseases. Patient education and self-management also constituted widely studied topics. Many studies on SLE found psychological interventions to improve quality of life. Studies on SSc found phototherapy and laser treatment to improve cutaneous disease manifestations. In summary, non-pharmacological management of SLE and SSc encompasses a wide range of interventions, which can be combined and provided either with or without adjunct pharmacological treatment but should not aim to substitute the latter when this is deemed required. While some management strategies i.e., physical exercise and patient education, are already established in current clinical practice in several centres, others e.g., phototherapy and laser treatment, show both feasibility and efficacy, yet require testing in more rigorous trials than those hitherto conducted.
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41.
  • Perez-Gonzalez, Pablo G., et al. (författare)
  • Life beyond 30 : Probing the-20 < M (UV) <-17 Luminosity Function at 8 < z < 13 with the NIRCam Parallel Field of the MIRI Deep Survey
  • 2023
  • Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 951:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the ultraviolet luminosity function and an estimate of the cosmic star formation rate density at 8 < z < 13 derived from deep NIRCam observations taken in parallel with the MIRI Deep Survey of the Hubble Ultra Deep Field (HUDF), NIRCam covering the parallel field 2. Our deep (40 hr) NIRCam observations reach an F277W magnitude of 30.8 (5 & sigma;), more than 2 mag deeper than JWST public data sets already analyzed to find high-redshift galaxies. We select a sample of 44 z > 8 galaxy candidates based on their dropout nature in the F115W and/or F150W filters, a high probability for their photometric redshifts, estimated with three different codes, being at z > 8, good fits based on & chi; (2) calculations, and predominant solutions compared to z < 8 alternatives. We find mild evolution in the luminosity function from z & SIM; 13 to z & SIM; 8, i.e., only a small increase in the average number density of & SIM;0.2 dex, while the faint-end slope and absolute magnitude of the knee remain approximately constant, with values & alpha; = - 2.2 & PLUSMN; 0.1, and M * = - 20.8 & PLUSMN; 0.2 mag. Comparing our results with the predictions of state-of-the-art galaxy evolution models, we find two main results: (1) a slower increase with time in the cosmic star formation rate density compared to a steeper rise predicted by models; (2) nearly a factor of 10 higher star formation activity concentrated in scales around 2 kpc in galaxies with stellar masses & SIM;10(8) M (& ODOT;) during the first 350 Myr of the universe, z & SIM; 12, with models matching better the luminosity density observational estimations & SIM;150 Myr later, by z & SIM; 9.
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42.
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43.
  • Tinetti, G., et al. (författare)
  • A chemical survey of exoplanets with ARIEL
  • 2018
  • Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
  • Tidskriftsartikel (refereegranskat)abstract
    • Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
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44.
  • Toledo, Estefania, et al. (författare)
  • Plasma lipidome and risk of atrial fibrillation: results from the PREDIMED trial
  • 2023
  • Ingår i: Journal of Physiology and Biochemistry. - 1138-7548 .- 1877-8755. ; 79:2, s. 355-364
  • Tidskriftsartikel (refereegranskat)abstract
    • The potential role of the lipidome in atrial fibrillation (AF) development is still widely unknown. We aimed to assess the association between lipidome profiles of the Prevención con Dieta Mediterránea (PREDIMED) trial participants and incidence of AF. We conducted a nested case–control study (512 incident centrally adjudicated AF cases and 735 controls matched by age, sex, and center). Baseline plasma lipids were profiled using a Nexera X2 U-HPLC system coupled to an Exactive Plus orbitrap mass spectrometer. We estimated the association between 216 individual lipids and AF using multivariable conditional logistic regression and adjusted the p values for multiple testing. We also examined the joint association of lipid clusters with AF incidence. Hitherto, we estimated the lipidomics network, used machine learning to select important network-clusters and AF-predictive lipid patterns, and summarized the joint association of these lipid patterns weighted scores. Finally, we addressed the possible interaction by the randomized dietary intervention. Forty-one individual lipids were associated with AF at the nominal level (p < 0.05), but no longer after adjustment for multiple-testing. However, the network-based score identified with a robust data-driven lipid network showed a multivariable-adjusted ORper+1SD of 1.32 (95% confidence interval: 1.16–1.51; p < 0.001). The score included PC plasmalogens and PE plasmalogens, palmitoyl-EA, cholesterol, CE 16:0, PC 36:4;O, and TG 53:3. No interaction with the dietary intervention was found. A multilipid score, primarily made up of plasmalogens, was associated with an increased risk of AF. Future studies are needed to get further insights into the lipidome role on AF. Current Controlled Trials number, ISRCTN35739639.
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45.
  • Tsoi, Alexander, et al. (författare)
  • Efficacy of lifestyle interventions in the management of systemic lupus erythematosus : a systematic review of the literature
  • 2024
  • Ingår i: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 44:5, s. 765-778
  • Forskningsöversikt (refereegranskat)abstract
    • We performed a systematic review to explore existing evidence regarding the efficacy of lifestyle interventions for the management of systemic lupus erythematosus (SLE). The search was conducted on the 22nd of June 2021 for publications between 1st of January 2000 and the date of search. Additional articles within the aforementioned timeframe and until December 2023 were added by hand searching. Databases utilized were Medline, Embase, Web of Science, and Cinahl. Lifestyle interventions were defined as any intervention encompassing one or more of the following: physical exercise, diet and nutrition, mental health, harmful exposures, sleep, and social relations. The Joanna Briggs Institute critical appraisal tools were used for risk of bias assessment. The search yielded 11,274 unique records, we assessed the full text of 199 records, and finally included 102 studies. Overall, the quality of the evidence is limited, and there were multiple sources of heterogeneity. The two domains most extensively researched were mental health (40 records) and physical exercise (39 records). Psychological interventions had a positive effect on depressive symptoms, anxiety, and health-related quality of life (HRQoL), whereas physical exercise improved fatigue, depressive symptoms, aerobic capacity, and physical functioning. Studies on diet and nutrition (15 records) support that low fat intake and Mediterranean diet may be beneficial for reducing cardiovascular risk, but large interventional studies are lacking. Studies on harmful exposures (7 records) support photoprotection and use of sunscreen. While studies imply benefits regarding disease burden and drug efficacy in non-smokers and regarding HRQoL in normal-weight patients, more survey is needed on tobacco smoking and alcohol consumption, as well as weight control strategies. Studies on social relations (1 record) and sleep (no records) were sparse or non-existent. In conclusion, psychosocial interventions are viable for managing depressive symptoms, and exercise appears essential for reducing fatigue and improving aerobic capacity and physical function. Photoprotection should be recommended to all patients. Lifestyle interventions should be considered a complement, not a substitute, to pharmacotherapy.
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46.
  • Webster, Christopher R., et al. (författare)
  • Background levels of methane in Mars' atmosphere show strong seasonal variations
  • 2018
  • Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 360:6393, s. 1093-1096
  • Tidskriftsartikel (refereegranskat)abstract
    • Variable levels of methane in the martian atmosphere have eluded explanation partly because the measurements are not repeatable in time or location. We report in situ measurements at Gale crater made over a 5-year period by the Tunable Laser Spectrometer on the Curiosity rover. The background levels of methane have a mean value 0.41 ± 0.16 parts per billion by volume (ppbv) (95% confidence interval) and exhibit a strong, repeatable seasonal variation (0.24 to 0.65 ppbv). This variation is greater than that predicted from either ultraviolet degradation of impact-delivered organics on the surface or from the annual surface pressure cycle. The large seasonal variation in the background and occurrences of higher temporary spikes (~7 ppbv) are consistent with small localized sources of methane released from martian surface or subsurface reservoirs.
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47.
  • Youssef, Lina, et al. (författare)
  • Fetal cardiac remodeling and dysfunction is associated with both preeclampsia and fetal growth restriction
  • 2020
  • Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378. ; 222:1, s. 1-79
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Preeclampsia and fetal growth restriction share some pathophysiologic features and are both associated with placental insufficiency. Fetal cardiac remodeling has been described extensively in fetal growth restriction, whereas little is known about preeclampsia with a normally grown fetus. Objective: To describe fetal cardiac structure and function in pregnancies complicated by preeclampsia and/or fetal growth restriction as compared with uncomplicated pregnancies. Study design: This was a prospective, observational study including pregnancies complicated by normotensive fetal growth restriction (n=36), preeclampsia with a normally grown fetus (n=35), preeclampsia with fetal growth restriction (preeclampsia with a normally grown fetus–fetal growth restriction, n=42), and 111 uncomplicated pregnancies matched by gestational age at ultrasound. Fetal echocardiography was performed at diagnosis for cases and recruitment for uncomplicated pregnancies. Cord blood concentrations of B-type natriuretic peptide and troponin I were measured at delivery. Univariate and multiple regression analysis were conducted. Results: Pregnancies complicated by preeclampsia and/or fetal growth restriction showed similar patterns of fetal cardiac remodeling with larger hearts (cardiothoracic ratio, median [interquartile range]: uncomplicated pregnancies 0.27 [0.23–0.29], fetal growth restriction 0.31 [0.26–0.34], preeclampsia with a normally grown fetus 0.31 [0.29–0.33), and preeclampsia with fetal growth restriction 0.28 [0.26–0.33]; P<.001) and more spherical right ventricles (right ventricular sphericity index: uncomplicated pregnancies 1.42 [1.25–1.72], fetal growth restriction 1.29 [1.22–1.72], preeclampsia with a normally grown fetus 1.30 [1.33–1.51], and preeclampsia with fetal growth restriction 1.35 [1.27–1.46]; P=.04) and hypertrophic ventricles (relative wall thickness: uncomplicated pregnancies 0.55 [0.48–0.61], fetal growth restriction 0.67 [0.58–0.8], preeclampsia with a normally grown fetus 0.68 [0.61–0.76], and preeclampsia with fetal growth restriction 0.66 [0.58–0.77]; P<.001). Signs of myocardial dysfunction also were observed, with increased myocardial performance index (uncomplicated pregnancies 0.78 z scores [0.32–1.41], fetal growth restriction 1.48 [0.97–2.08], preeclampsia with a normally grown fetus 1.15 [0.75–2.17], and preeclampsia with fetal growth restriction 0.45 [0.54–1.94]; P<.001) and greater cord blood B-type natriuretic peptide (uncomplicated pregnancies 14.2 [8.4–30.9] pg/mL, fetal growth restriction 20.8 [13.1–33.5] pg/mL, preeclampsia with a normally grown fetus 31.8 [16.4–45.8] pg/mL and preeclampsia with fetal growth restriction 37.9 [15.7–105.4] pg/mL; P<.001) and troponin I as compared with uncomplicated pregnancies. Conclusion: Fetuses of preeclamptic mothers, independently of their growth patterns, presented cardiovascular remodeling and dysfunction in a similar fashion to what has been previously described for fetal growth restriction. Future research is warranted to better elucidate the mechanism(s) underlying fetal cardiac adaptation in these conditions.
  •  
48.
  • Zanti, Maria, et al. (författare)
  • A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2
  • 2023
  • Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 2023
  • Tidskriftsartikel (refereegranskat)abstract
    • A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
  •  
49.
  • Zhukova, Valentina, et al. (författare)
  • Free Space Microwave Sensing of Carbon Fiber Composites with Ferromagnetic Microwire Inclusions
  • 2024
  • Ingår i: IEEE Sensors Letters. - 2475-1472. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We provide new experimental results on studies of composites with glass-coated ferromagnetic microwires aligned with the requirements of carbon composites. This work focuses on the free space microwave measurements of composites made from carbon fibers and ferromagnetic microwires inclusion focusing on the electromagnetic properties. We prepared several glass-coated microwires and selected Co-based microwires with optimum soft magnetic properties and high magnetoimpedance effect for composite fabrication. We observed that by using a low frequency modulating AC magnetic field parallel oriented to the ferromagnetic microwires allows us to distinguish the microwave signals originated from the ferromagnetic microwires inclusions from the response generated by the carbon fibers. The location of carbon fibers near magnetic microwires has a critical effect on the response signals (parameters S amplitude) obtained from such composites.
  •  
50.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
  •  
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