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| 4. |
- Emery, Carolyn A, et al.
(författare)
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Establishing outcome measures in early knee osteoarthritis
- 2019
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Ingår i: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1759-4804 .- 1759-4790. ; 15:7, s. 438-448
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Forskningsöversikt (refereegranskat)abstract
- The classification and monitoring of individuals with early knee osteoarthritis (OA) are important considerations for the design and evaluation of therapeutic interventions and require the identification of appropriate outcome measures. Potential outcome domains to assess for early OA include patient-reported outcomes (such as pain, function and quality of life), features of clinical examination (such as joint line tenderness and crepitus), objective measures of physical function, levels of physical activity, features of imaging modalities (such as of magnetic resonance imaging) and biochemical markers in body fluid. Patient characteristics such as adiposity and biomechanics of the knee could also have relevance to the assessment of early OA. Importantly, research is needed to enable the selection of outcome measures that are feasible, reliable and validated in individuals at risk of knee OA or with early knee OA. In this Perspectives article, potential outcome measures for early symptomatic knee OA are discussed, including those measures that could be of use in clinical practice and/or the research setting.
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| 5. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Pelkmans, L., et al.
(författare)
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Monitoring the Impact of Sustainability Certification in Relation to Biomass Use for Energy
- 2012
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Ingår i: EUBCE 2012 proceedings. - 9788889407547 ; , s. 2013-2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Since the public has expressed concern about unintended consequences associated with potentially unsustainable biomass production and use for energy (or biofuels), producers of biomass feedstocks in the private sector as well as governmental and non-governmental organisations have initiated many generally unlinked efforts to define 'sustainable' bioenergy production and supply chains. These 'sustainability' standards may be implemented through certification systems involving 3rd party audit, and influence production systems and trade of bioenergy products from producers to consumers of ‘green' energy. At present numerous biomass and biofuel sustainability certification systems are being developed or implemented by a variety of private and public organisations. Systems are applicable to different feedstock production sectors (forests, agricultural crops), different bioenergy products (relatively unprocessed forest residues, ethanol, biodiesel, electricity), and whole or segments of supply chains (production system, chain of custody from growers to energy consumers). It is expected that such a wide range of systems, developed largely without coordination among the organisations involved, could be problematic for all stakeholders along the supply chain in individual sectors and for those involved in deployment of bioenergy systems globally. These are individual feedstock producers, companies and commodity sectors that must comply with these systems either to maintain market access and share or to comply with legislative mandates, and also consumers who prefer to purchase certified green energy, and regulatory agencies and local to national governments that may be involved in enforcing sustainability standards. The potential for confusion among the actors, depression of markets, and unnecessary restrictions on sustainable trade seems high. Within IEA Bioenergy a strategic study was initiated between Task 40, Task 43 and Task 38 to monitor the actual implementation process of sustainability certification of bioenergy, evaluate how stakeholders are affected by certification initiatives, quantify the anticipated impact on worldwide bioenergy trade, assess the level of coordination among schemes, and make recommendations to remove barriers which may depress markets and reduce sustainable trade. Interaction with different stakeholder groups is one of the main objectives of this study, so we anticipate the recommendations being representative of the whole bioenergy certification sector and therefore having high potential to improve an otherwise uncoordinated interest in ensuring bioenergy trade is sustainable.
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| 7. |
- Pilegaard, S. P., et al.
(författare)
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Psychosocial wellbeing shortly after allocation to a freeze-all strategy compared with a fresh transfer strategy in women and men: a sub-study of a randomized controlled trial
- 2023
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Ingår i: Human Reproduction. - 0268-1161. ; 38:11, s. 2175-2186
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION Is the psychosocial wellbeing affected in women and men shortly after allocation to a freeze-all strategy with postponement of embryo transfer compared to a fresh transfer strategy?SUMMARY ANSWER In general, psychosocial wellbeing (i.e. emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit) was similar in women and men allocated to a freeze-all versus those allocated to a fresh-transfer strategy 6 days after disclosure of treatment strategy (i.e. 4 days after oocyte retrieval), although women in the freeze-all group reported a slightly higher degree of depressive symptoms and mood swings compared to women in the fresh transfer group.WHAT IS KNOWN ALREADY The use of a freeze-all strategy, i.e. freezing of the entire embryo cohort followed by elective frozen embryo transfer in subsequent cycles has increased steadily over the past decade in assisted reproductive technology (ART). This strategy essentially eliminates the risk of ovarian hyperstimulation syndrome and has proven beneficial regarding some reproductive outcomes in subgroups of women. However, patients experience a longer time interval between oocyte retrieval and embryo transfer, hence a longer time to pregnancy, possibly adding additional stress to the ART treatment. So far, little focus has been on the possible psychosocial strains caused by postponement of embryo transfer.STUDY DESIGN, SIZE, DURATION This is a self-reported questionnaire based sub-study of a multicentre randomized controlled trial (RCT) including 460 women and 396 male partners initiating their first, second, or third treatment cycle of invitro fertilisation or intracytoplasmic sperm injection (ICSI) from May 2016 to September 2018. This sub-study was included in the primary project protocol and project plan for the RCT, as psychosocial wellbeing was considered a secondary outcome.PARTICIPANTS/MATERIALS, SETTING, METHODS Women from eight public fertility clinics in Denmark and Sweden and one private clinic in Spain were randomized in a 1:1 ratio on the day of inclusion (menstrual cycle day 2 or 3) to either a freeze-all strategy with postponement of embryo transfer to a subsequent modified natural menstrual cycle or a fresh transfer strategy with embryo transfer in the hormone stimulated cycle. Treatment allocation was blinded until the day of the ovulation trigger. Women and their male partners were asked to complete a validated self-reported questionnaire 6 days after unblinding of treatment group allocation, corresponding to 4 days after oocyte retrieval, investigating their psychosocial wellbeing related to the treatment defined as emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit. The questionnaire included items from the Copenhagen Multi-Centre Psychosocial Infertility (COMPI) Fertility Problem Stress Scales and the COMPI Marital Benefit Measure.MAIN RESULTS AND THE ROLE OF CHANCE Baseline characteristics were comparable between the two groups for both women and men. In total, response rates were 90.7% for women and 90.2% for men. In the freeze-all group, 207 women and 179 men completed the questionnaire compared with 204 women and 178 men in the fresh transfer group. Men in the two treatment groups did not differ in any of the explored aspects of psychosocial wellbeing (i.e. emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit) 6 days after disclosure of treatment strategy. Women in the freeze-all group reported a slightly higher degree of depressive symptoms (P = 0.045) and mood swings (P = 0.001) (i.e. variables included in 'emotional reactions to treatment') compared to women in the fresh transfer group. When adjusted for multiple testing, depressive symptoms were no longer significantly different between the two groups. No additional differences in psychosocial wellbeing were found. Self-reported quality-of-life during treatment was also rated as similar between the two groups in both women and men, but was slightly lower than they would rate their quality-of-life when not in fertility treatment.LIMITATIONS, REASONS FOR CAUTION Although response rates were high, selection bias cannot be excluded. As this study was an RCT, we assume that psychosocial characteristics of the participants were equally distributed in the two groups, thus it is unlikely that the identified psychosocial differences between the freeze-all and fresh transfer group were present already at baseline. Furthermore, the questionnaire was completed as a one-time assessment 4 days after oocyte retrieval, thus not reflecting the whole treatment process, whereas an assessment after the full completed treatment cycle is needed to draw firm conclusions about the psychosocial consequences of the whole waiting period. However, a question posted that late would be highly biased on whether or not a pregnancy had been achieved.WIDER IMPLICATIONS OF THE FINDINGS The results indicate that individuals in the freeze-all group exhibited slightly higher levels of depressive symptoms and mood swings compared to those in the fresh transfer group. Nevertheless, it is important to note that any worries related to potential emotional strains stemming from delaying embryo transfer should not overshadow the adoption of a freeze-all approach in cases where it is clinically recommended. As long as patients are provided with comprehensive information about the treatment strategy before initiating the process, it is worth emphasising that other aspects of psychosocial wellbeing were comparable between the two groups.STUDY FUNDING/COMPETING INTEREST(S) The study is part of the Reprounion collaborative study, co-financed by the European Union, Interreg V oresund-Kattegat-Skagerrak. L.P. reports financial support from Merck A/S. H.S.N. reports grants from Freya Biosciences ApS, Ferring Pharmaceuticals, BioInnovation Institute, Ministry of Education, Novo Nordic Foundation, Augustinus Fonden, Oda og Hans Svenningsens Fond, Demant Fonden, Ole Kirks Fond and Independent Research Fund Denmark and personal fees from Ferring Pharmaceuticals, Merck A/S, Astra Zeneca, Cook Medical, IBSA Nordic and Gedeon Richter. H.S.N is founder and chairman of the Maternity Foundation and co-developed the Safe Delivery App (non-profit). N.C.F. reports grants from Gedeon Richter, Merck A/S, Cryos International and financial support from Ferring Pharmaceuticals, Merck A/S and Gedeon Richter. N.C.F. is chairman in the steering committee for the guideline groups for The Danish Fertility Society (non-profit). P.H. reports honoraria from Merch A/S, IBSA Nordic and Gedeon Richter. A.L.M.E. reports grants and financial support from Merck A/S and Gedeon Richter. A.P. reports grants from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S and personal fees from Preglem S.A., Novo Nordic Foundation, Ferring Pharmaceuticals, Gedeon Richter, Cryos International, Merch A/S, Theramex and Organon and the lend of embryoscope to the institution from Gedeon Richter. All other authors declare no conflict of interest.
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| 8. |
- Cadenas, J., et al.
(författare)
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Regulation of human oocyte maturation in vivo during the final maturation of follicles
- 2023
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 38:4, s. 686-700
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Which substances and signal transduction pathways are potentially active downstream to the effect of FSH and LH in the regulation of human oocyte maturation in vivo? SUMMARY ANSWER: The regulation of human oocyte maturation appears to be a multifactorial process in which several different signal transduction pathways are active. WHAT IS KNOWN ALREADY: Many studies in animal species have provided insight into the mechanisms that govern the final maturation of oocytes. Currently, these studies have identified several different mechanisms downstream to the effects of FSH and LH. Some of the identified mechanisms include the regulation of cAMP/cGMP levels in oocytes involving C-type natriuretic peptide (CNP), effects of epidermal growth factor (EGF)-related peptides such as amphiregulin (AREG) and/or epiregulin (EREG), effect of TGF-β family members including growth differentiation factor 9 (GDF9) and morphogenetic protein 15 (BMP15), activins/inhibins, follicular fluid meiosis activating sterol (FF-MAS), the growth factor midkine (MDK), and several others. However, to what extent these pathways and mechanisms are active in humans in vivo is unknown. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 50 women undergoing fertility treatment in a standard antagonist protocol at a university hospital affiliated fertility clinic in 2016-2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated the substances and signalling pathways potentially affecting human oocyte maturation in follicular fluid (FF) and granulosa cells (GCs) collected at five time points during the final maturation of follicles. Using ELISA measurement and proteomic profiling of FF and whole genome gene expression in GC, the following substances and their signal transduction pathways were collectively evaluated: CNP, the EGF family, inhibin-A, inhibin-B, activins, FF-MAS, MDK, GDF9, and BMP15. MAIN RESULTS AND THE ROLE OF CHANCE: All the evaluated substances and signal transduction pathways are potentially active in the regulation of human oocyte maturation in vivo except for GDF9/BMP15 signalling. In particular, AREG, inhibins, and MDK were significantly upregulated during the first 12-17 h after initiating the final maturation of follicles and were measured at significantly higher concentrations than previously reported. Additionally, the genes regulating FF-MAS synthesis and metabolism were significantly controlled in favour of accumulation during the first 12-17 h. In contrast, concentrations of CNP were low and did not change during the process of final maturation of follicles, and concentrations of GDF9 and BMP15 were much lower than reported in small antral follicles, suggesting a less pronounced influence from these substances. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR CAUTION: Although GC and cumulus cells have many similar features, it is a limitation of the current study that information for the corresponding cumulus cells is not available. However, we seldom recovered a cumulus-oocyte complex during the follicle aspiration from 0 to 32 h. WIDER IMPLICATIONS OF THE FINDINGS: Delineating the mechanisms governing the regulation of human oocyte maturation in vivo advances the possibility of developing a platform for IVM that, as for most other mammalian species, results in healthy offspring with good efficacy. Mimicking the intrafollicular conditions during oocyte maturation in vivo in small culture droplets during IVM may enhance oocyte nuclear and cytoplasmic maturation. The primary outlook for such a method is, in the context of fertility preservation, to augment the chances of achieving biological children after a cancer treatment by subjecting oocytes from small antral follicles to IVM. Provided that aspiration of oocytes from small antral follicles in vivo can be developed with good efficacy, IVM may be applied to infertile patients on a larger scale and can provide a cheap alternative to conventional IVF treatment with ovarian stimulation. Successful IVM has the potential to change current established techniques for infertility treatment. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the University Hospital of Copenhagen, Rigshospitalet, the Independent Research Fund Denmark (grant number 0134-00448), and the Interregional EU-sponsored ReproUnion network. There are no conflicts of interest to be declared.
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| 13. |
- Plymale, Andrew E., et al.
(författare)
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Niche Partitioning of Microbial Communities at an Ancient Vitrified Hillfort : Implications for Vitrified Radioactive Waste Disposal
- 2021
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Ingår i: Geomicrobiology Journal. - : Taylor & Francis. - 0149-0451 .- 1521-0529. ; 38:1, s. 36-56
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Tidskriftsartikel (refereegranskat)abstract
- Because microbes cannot be eliminated from radioactive waste disposal facilities, the consequences of bio-colonization must be understood. At a pre-Viking era vitrified hillfort, Broborg, Sweden, anthropogenic glass has been subjected to bio-colonization for over 1,500 years. Broborg is used as a habitat analogue for disposed radioactive waste glass to inform how microbial processes might influence long-term glass durability. Electron microscopy and DNA sequencing of surficial material from the Broborg vitrified wall, adjacent soil, and general topsoil show that the ancient glass supports a niche microbial community of bacteria, fungi, and protists potentially involved in glass alteration. Communities associated with the vitrified wall are distinct and less diverse than soil communities. The vitrified niche of the wall and adjacent soil are dominated by lichens, lichen-associated microbes, and other epilithic, endolithic, and epigeic organisms. These organisms exhibit potential bio-corrosive properties, including silicate dissolution, extraction of essential elements, and secretion of geochemically reactive organic acids, that could be detrimental to glass durability. However, long-term biofilms can also possess a homeostatic function that could limit glass alteration. This study documents potential impacts that microbial colonization and niche partitioning can have on glass alteration, and subsequent release of radionuclides from a disposal facility for vitrified radioactive waste.
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| 14. |
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| 15. |
- Ulugut, Hulya, et al.
(författare)
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Clinical recognition of frontotemporal dementia with right anterior temporal predominance : A multicenter retrospective cohort study
- 2024
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Ingår i: Alzheimer's and Dementia. - 1552-5260.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS: Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS: Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION: This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. Highlights: This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.
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| 16. |
- Bergman, Susanna L., et al.
(författare)
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In-situ studies of oxidation/reduction of copper in Cu-CHA SCR catalysts: Comparison of fresh and SO2-poisoned catalysts
- 2020
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Ingår i: Applied Catalysis B: Environmental. - : Elsevier BV. - 0926-3373 .- 1873-3883. ; 269
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Tidskriftsartikel (refereegranskat)abstract
- SO2-poisoning results in deactivation of Cu-CHA SCR under standard SCR conditions; however regeneration at 700 °C completely restores the SCR performance. To understand the nature of these effects, Cu-species in the fresh and poisoned catalysts were characterized by in-situ temperature-dependent time-resolved Cu K-edge X-ray absorption spectroscopy using the multivariate curve resolution alternating least squares (MCR-ALS) approach and continuous Cauchy wavelet transforms. The extracted chemically-meaningful reference spectra of Cu-species were analyzed by DFT-assisted XANES calculations. Cu-bisulfates were found as the most energetically favorable poisoned Cu-species. The response of Cu-species to a reducing environment differs in the fresh and SO2-poisoned catalysts. Differences in reducibility are related to the formation of quasi-linear Cu-complexes in the SO2-poisoned catalyst formed during heating in H2/He. Heating in H2/He leads to partial desulfurization of the poisoned catalyst. Cooling in H2/He after heating results in more facile formation of Cu-metal clusters in fresh catalyst than in SO2-poisoned.
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| 17. |
- Brantsæter, A. L., et al.
(författare)
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Diet matters, particularly in pregnancy – Results from MoBa studies of maternal diet and pregnancy outcomes
- 2014
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Ingår i: Norsk Epidemiologi. - 0803-2491. ; 24:1-2, s. 63-77
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Forskningsöversikt (refereegranskat)abstract
- Awareness that maternal diet may influence the outcome of pregnancy as well as the long-term health of mother and child has increased in recent years. A new food frequency questionnaire (FFQ) was developed and validated specifically for the Norwegian Mother and Child Cohort Study (MoBa). The MoBa FFQ is a semi-quantitative tool which covers the average intake of food, beverages and dietary supplements during the first 4 to 5 months of pregnancy. It includes questions about intakes of 255 foods and dishes and was used from 2002 onwards. Data assessed by the MoBa FFQ is available for 87,700 pregnancies. Numerous sub-studies have examined associations between dietary factors and health outcomes in MoBa. The aim of this paper is to summarize the results from 19 studies of maternal diet and pregnancy outcomes, which is the complete collection of studies based on the MoBa FFQ and published before September 2014. The overall research question is whether maternal diet – from single substances to dietary patterns – matters for pregnancy outcome. The pregnancy outcomes studied till now include birth size measures, infants being small and large for gestational age, pregnancy duration, preterm delivery, preeclampsia, as well as maternal gestational weight gain and postpartum weight retention. As a whole, the results from these studies corroborate that the current dietary recommendations to pregnant women are sound and that maternal diet during pregnancy is likely to contribute to reduce the risk of pregnancy complications including preterm birth, preeclampsia, and reduced foetal growth. The results provide supporting evidence for recommending pregnant women to consume vegetables, fruit, whole grain, fish, dairy, and water regularly and lower the intake of sugar sweetened beverages, processed meat products and salty snacks. The results showing negative impact of even low levels of environmental contaminants support the precautionary advice on consumption of foods containing these. New findings are that particularly lean fish explained the positive association between seafood intake and foetal growth, and the indications of a protective effect of probiotic and antimicrobial foods on pregnancy outcomes. This points to the importance of diet composition for a healthy gut flora and the body’s immune response. Although these studies are observational and cannot infer causality, the results identify diet as an important modifiable lifestyle factor, suggesting that healthy eating, defined as following the official recommendations, is particularly important in pregnancy.
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| 18. |
- Capo, Eric, et al.
(författare)
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Lake sedimentary dna research on past terrestrial and aquatic biodiversity: Overview and recommendations
- 2021
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Ingår i: Quaternary. - : MDPI. - 2571-550X. ; 4:1
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Forskningsöversikt (refereegranskat)abstract
- The use of lake sedimentary DNA to track the long-term changes in both terrestrial and aquatic biota is a rapidly advancing field in paleoecological research. Although largely applied nowadays, knowledge gaps remain in this field and there is therefore still research to be conducted to ensure the reliability of the sedimentary DNA signal. Building on the most recent literature and seven original case studies, we synthesize the state-of-the-art analytical procedures for effective sampling, extraction, amplification, quantification and/or generation of DNA inventories from sedimentary ancient DNA (sedaDNA) via high-throughput sequencing technologies. We provide recommendations based on current knowledge and best practises.
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| 19. |
- Clayton, Emma L., et al.
(författare)
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Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation
- 2017
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 26:5, s. 873-887
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like changes in social behaviour. These data are the first to show neurodegeneration in mice expressing mutant CHMP2B and indicate that our mouse model is able to recapitulate neurodegenerative changes observed in FTD. Neuroinflammation has been increasingly implicated in neurodegeneration, including FTD. Therefore, we investigated neuroinflammation in our CHMP2B mutant mice. We observed very early microglial proliferation that develops into a clear pro-inflammatory phenotype at late stages. Importantly, we also observed a similar inflammatory profile in CHMP2B patient frontal cortex. Aberrant microglial function has also been implicated in FTD caused by GRN, MAPT and C9orf72 mutations. The presence of early microglial changes in our CHMP2B mutant mice indicates neuroinflammation may be a contributing factor to the neurodegeneration observed in FTD.
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| 20. |
- El-Sayed, Najib M., et al.
(författare)
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The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease.
- 2005
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5733, s. 409-15
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
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| 21. |
- Freitas, Flavio L M, et al.
(författare)
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Biodiversity values of Brazilian native vegetation – How much is protected by the Forest Act?
- 2018
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Konferensbidrag (refereegranskat)abstract
- Human-induced land use change (LUC) is the most important driver of biodiversity loss. In Brazil, this process is particularly concerning considering that here are the most extensive tracts of tropical forest and other rare habitat types which host unique biodiversity. The preservation of much of this area is highly dependent on the implementation of the Forest Act, the central legal framework regulating the conservation of native vegetation on private land in Brazil. Recent studies provide a modelling framework for assessing the impacts of the Forest Act on the protection of native vegetation and associated carbon stocks for the entire Brazilian territory. However, there is not sufficient knowledge on the efficiency of this legislation in protecting areas of high and unique biodiversity in Brazil.This study aims to apply the existing land use governance assessment (LUGA) model to quantify the extent to which the Forest Act protects biodiversity. For this purpose, we construct indicators at fine-scale levels to capture the multiple dimensions of biodiversity (species richness, genetic, and functional diversity) and how these are related to the native vegetation. Using state-of-the-art databases of species distribution data, GIS-based modeling frameworks are developed and adapted to identify values of native vegetation related to the preservation of biodiversity in general, and endangered species in particular, and ecological connectivity. The results are evaluated for Brazilian regions where the LUC pressure is recognized to be most significant. The final model output consists of geoexplicit indicators at a high resolution, which informs about the degree of biodiversity protection provided by the Forest Act. The information provided by this project can support decision-making related to the selection of areas of high importance for biodiversity protection at local and regional levels. Further, it can potentially contribute to efficient use of resources and improved effectiveness of incentive mechanisms in promoting conservation of unprotected native vegetation of high biodiversity value.
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| 22. |
- Höglinger, Günter U, et al.
(författare)
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Clinical diagnosis of progressive supranuclear palsy : The movement disorder society criteria
- 2017
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 32:6, s. 853-864
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Tidskriftsartikel (refereegranskat)abstract
- Background: PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome. Objective: We aimed to provide an evidence- and consensus-based revision of the clinical diagnostic criteria for PSP. Methods: We searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy-confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2-day meeting, and refined in three further Delphi rounds. Results: Defined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context-dependent exclusion criteria. We identified four functional domains (ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction) as clinical predictors of PSP. Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features. Conclusions: Here, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence.
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| 23. |
- Jensen, L. L., et al.
(författare)
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Paediatric ventilation treatment of acute lung injury in Nordic intensive care units
- 2015
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 59:5, s. 568-575
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTreatment of acute respiratory distress syndrome (ARDS) in children is largely based on extrapolated knowledge obtained from adults and which varies between different hospitals. This study explores ventilation treatment strategies for children with ARDS in the Nordic countries, and compares these with international practice. MethodsIn October 2012, a questionnaire covering ventilation treatment strategies for children aged 1 month to 6 years of age with ARDS was sent to 21 large Nordic intensive care units that treat children with ARDS. Pre-terms and children with congenital conditions were excluded. ResultsEighteen of the 21 (86%) targeted intensive care units responded to the questionnaire. Fiftypercent of these facilities were paediatric intensive care units. Written guidelines existed in 44% of the units. Fiftypercent of the units frequently used cuffed endotracheal tubes. Ventilation was achieved by pressure control for 89% vs. volume control for 11% of units. Bronchodilators were used by all units, whereas steroids usage was 83% and surfactant 39%. Inhaled nitric oxide and high frequency oscillation were available in 94% of the units. Neurally adjusted ventilator assist was used by 44% of the units. Extracorporeal membrane oxygenation could be started in 44% of the units. ConclusionVentilation treatment strategies for paediatric ARDS in the Nordic countries are relatively uniform and largely in accordance with international practice. The use of steroids and surfactant is more frequent than shown in other studies.
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| 24. |
- Lundberg, C, et al.
(författare)
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Dementia and driving: an attempt at consensus
- 1997
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Ingår i: Alzheimer disease and associated disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341. ; 11:1, s. 28-37
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Tidskriftsartikel (refereegranskat)
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| 25. |
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| 26. |
- Matthews, Bethany E., et al.
(författare)
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Micro- and Nanoscale Surface Analysis of Late Iron Age Glass from Broborg, a Vitrified Swedish Hillfort
- 2023
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Ingår i: Microscopy and Microanalysis. - : Oxford University Press. - 1431-9276 .- 1435-8115. ; 29:1, s. 50-68
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Tidskriftsartikel (refereegranskat)abstract
- Archaeological glasses with prolonged exposure to biogeochemical processes in the environment can be used to understand glass alteration, which is important for the safe disposal of vitrified nuclear waste. Samples of mafic and felsic glasses with different chemistries, formed from melting amphibolitic and granitoid rocks, were obtained from Broborg, a Swedish Iron Age hillfort. Glasses were excavated from the top of the hillfort wall and from the wall interior. A detailed microscopic, spectroscopic, and diffraction study of surficial textures and chemistries were conducted on these glasses. Felsic glass chemistry was uniform, with a smooth surface showing limited chemical alteration (<150 nm), irrespective of the position in the wall. Mafic glass was heterogeneous, with pyroxene, spinel, feldspar, and quartz crystals in the glassy matrix. Mafic glass surfaces in contact with topsoil were rougher than those within the wall and had carbon-rich material consistent with microbial colonization. Limited evidence for chemical or physical alteration of mafic glass was found; the thin melt film that coated all exposed surfaces remained intact, despite exposure to hydraulically unsaturated conditions, topsoil, and associated microbiome for over 1,500 years. This supports the assumption that aluminosilicate nuclear waste glasses will have a high chemical durability in near-surface disposal facilities.
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| 27. |
- Mesilov, Vitaly, et al.
(författare)
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Impact of Biodiesel-Based Phosphorus and Sulfur on Copper Speciation of Cu-SSZ-13 Catalysts : XAFS Scanning during H-2-TPR
- 2022
-
Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 126:7, s. 3385-3396
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Tidskriftsartikel (refereegranskat)abstract
- Biodiesel is a promising renewable fuel, which may help to limit our dependence on fossil fuels. However, the presence of contaminants in biodiesel can affect the Cu speciation of the Cu-SSZ-13 selective catalytic reduction (SCR) catalyst, resulting in its deactivation and decreased durability. In situ Cu K-edge X-ray absorption fine structure (XAFS) scanning during a temperature-programmed reduction in hydrogen (H-2-TPR) has been applied here for the analysis of Cu speciation in Cu-SSZ-13 catalysts aged using pure and contaminated biodiesel fuels. XAFS data were analyzed using the multivariate curve resolution alternating least-squares (MCR-ALS) method. While only reduction from Cu-II to Cu-I was observed at temperatures below 500 degrees C for the catalyst aged using pure biodiesel, a one-step reduction of Cu-II to Cu-0 at temperatures between 400 and 500 degrees C was found for the catalyst aged using P-doped biodiesel. The transformation of isolated CuII species to Cu-II clusters was suggested for the catalyst as a result of aging using P-doped biodiesel. The catalyst aged using S-doped biodiesel showed mainly the reduction of isolated Cu-II to Cu-I, which was inhibited as compared to that observed for the catalyst aged using pure biodiesel. The reduction of the catalyst aged using P+S-doped biodiesel led to the reduction of Cu-II to both Cu-I and Cu-0. The phosphorus was responsible for the formation of Cu-II clusters during aging of the catalyst using P+S-doped biodiesel. This study reveals that the presence of phosphorus in biofuels should be strictly regulated to avoid major changes in the Cu speciation of Cu-SSZ-13 catalysts.
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| 28. |
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| 29. |
- Roeder, SS, et al.
(författare)
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Evidence for postnatal neurogenesis in the human amygdala
- 2022
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 366-
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Tidskriftsartikel (refereegranskat)abstract
- The human amygdala is involved in processing of memory, decision-making, and emotional responses. Previous studies suggested that the amygdala may represent a neurogenic niche in mammals. By combining two distinct methodological approaches, lipofuscin quantification and 14C-based retrospective birth dating of neurons, along with mathematical modelling, we here explored whether postnatal neurogenesis exists in the human amygdala. We investigated post-mortem samples of twelve neurologically healthy subjects. The average rate of lipofuscin-negative neurons was 3.4%, representing a substantial proportion of cells substantially younger than the individual. Mass spectrometry analysis of genomic 14C-concentrations in amygdala neurons compared with atmospheric 14C-levels provided evidence for postnatal neuronal exchange. Mathematical modelling identified a best-fitting scenario comprising of a quiescent and a renewing neuronal population with an overall renewal rate of >2.7% per year. In conclusion, we provide evidence for postnatal neurogenesis in the human amygdala with cell turnover rates comparable to the hippocampus.
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| 30. |
- Smith, Ruben, et al.
(författare)
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Cholinergic neuronal defect without cell loss in Huntington's disease.
- 2006
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 15:21, s. 3119-3131
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG-repeat expansion in the huntingtin (IT15) gene. The striatum is one of the regions most affected by neurodegeneration, resulting in the loss of the medium-sized spiny neurons. Traditionally, the large cholinergic striatal interneurons are believed to be spared. Recent studies demonstrate that neuronal dysfunction without cell death also plays an important role in early and mid-stages of the disease. Here, we report that cholinergic transmission is affected in a HD transgenic mouse model (R6/1) and in tissues from HD patients. Stereological analysis shows no loss of cholinergic neurons in the striatum or septum in R6/1 mice. In contrast, the levels of mRNA and protein for vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) are decreased in the striatum and cortex, and acetylcholine esterase activity is lowered in the striatum of R6/1 mice already at young ages. Accordingly, VAChT is also reduced in striatal tissue from patients with HD. The decrease of VAChT in the patient samples studied is restricted to the striatum and does not occur in the hippocampus or the spinal cord. The expression and localization of REST/NRSF, a transcriptional regulator for the VAChT and ChAT genes, are not altered in cholinergic neurons. We show that the R6/1 mice exhibit severe deficits in learning and reference memory. Taken together, our data show that the cholinergic system is dysfunctional in R6/1 and HD patients. Consequently, they provide a rationale for testing of pro-cholinergic drugs in this disease.
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| 31. |
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| 32. |
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| 33. |
- Watt, F. E., et al.
(författare)
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Towards prevention of post-traumatic osteoarthritis : report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury
- 2019
-
Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:1, s. 23-33
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. Design: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. Results: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. Conclusions: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.
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| 34. |
- Whittaker, Jackie L., et al.
(författare)
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Toward designing human intervention studies to prevent osteoarthritis after knee injury : A report from an interdisciplinary OARSI 2023 workshop
- 2024
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Ingår i: Osteoarthritis and Cartilage Open. - 2665-9131. ; 6:2
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.
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| 35. |
- Abbott, Allan, 1978-, et al.
(författare)
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Understanding the role of diabetes in the osteoarthritis disease and treatment process: a study protocol for the Swedish Osteoarthritis and Diabetes (SOAD) cohort
- 2019
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 9:12
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide. Metabolic comorbidities such as type II diabetes occur with a higher rate in people with OA than in the general population. Several factors including obesity, hyperglycaemia toxicity and physical inactivity have been suggested as potential links between diabetes and OA, and have been shown to negatively impact patients' health and quality of life. However, little is known on the role of diabetes in determining the outcome of non-surgical and surgical management of OA, and at the same time, how different OA interventions may affect diabetes control. Thus, the overall aim of this project is to explore (1) the impact of diabetes on the outcome of non-surgical and surgical OA treatments and (2) the impact of non-surgical and surgical OA treatments on diabetes control. Methods and analysis The study cohort is based on prospectively ascertained register data on a national level in Sweden. Data from OA patients who received a first-line non-surgical intervention and are registered in the National Quality Register for Better Management of Patients with Osteoarthritis will be merged with data from the Swedish Knee and Hip Arthroplasty Registers and the National Diabetes Register. Additional variables regarding patients' use of prescribed drugs, comorbidities, socioeconomic status and cause of death will be obtained through other national health and population data registers. The linkage will be performed on an individual level using unique personal identity numbers. Ethics and dissemination This study received ethical approval (2019-02570) from the Swedish Ethical Review Authority. Results from this cohort will be submitted to peer-reviewed scientific journals and reported at the leading national and international meetings in the field.
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| 36. |
- Abella, J., et al.
(författare)
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SAFEXPLAIN : Safe and Explainable Critical Embedded Systems Based on AI
- 2023
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Ingår i: Proceedings -Design, Automation and Test in Europe, DATE. - : Institute of Electrical and Electronics Engineers Inc.. - 9783981926378
-
Konferensbidrag (refereegranskat)abstract
- Deep Learning (DL) techniques are at the heart of most future advanced software functions in Critical Autonomous AI-based Systems (CAIS), where they also represent a major competitive factor. Hence, the economic success of CAIS industries (e.g., automotive, space, railway) depends on their ability to design, implement, qualify, and certify DL-based software products under bounded effort/cost. However, there is a fundamental gap between Functional Safety (FUSA) requirements on CAIS and the nature of DL solutions. This gap stems from the development process of DL libraries and affects high-level safety concepts such as (1) explainability and traceability, (2) suitability for varying safety requirements, (3) FUSA-compliant implementations, and (4) real-time constraints. As a matter of fact, the data-dependent and stochastic nature of DL algorithms clashes with current FUSA practice, which instead builds on deterministic, verifiable, and pass/fail test-based software. The SAFEXPLAIN project tackles these challenges and targets by providing a flexible approach to allow the certification - hence adoption - of DL-based solutions in CAIS building on: (1) DL solutions that provide end-to-end traceability, with specific approaches to explain whether predictions can be trusted and strategies to reach (and prove) correct operation, in accordance to certification standards; (2) alternative and increasingly sophisticated design safety patterns for DL with varying criticality and fault tolerance requirements; (3) DL library implementations that adhere to safety requirements; and (4) computing platform configurations, to regain determinism, and probabilistic timing analyses, to handle the remaining non-determinism.
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| 37. |
- Ahmad Kiadaliri, Aliasghar, et al.
(författare)
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Association of knee pain and different definitions of knee osteoarthritis with health-related quality of life : A population-based cohort study in southern Sweden
- 2016
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Ingår i: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: While the impact of knee pain and knee osteoarthritis (OA) on health-related quality of life (HRQoL) has been investigated in the literature, there is a lack of knowledge on the impact of different definitions of OA on HRQoL. The main aim of this study was to measure and compare the impact of knee OA and its different definitions on HRQoL in the general population. Methods: A random sample of 1300 participants from Malmö, Sweden with pain in one or both knees in the past 12 months with duration ≥4 weeks and 650 participants without were invited to clinical and radiographic knee examination. A total of 1527 individuals with a mean (SD) age 69.4 (7.2) participated and responded to both generic (EQ-5D-3L) and disease-specific (the Knee injury and Osteoarthritis Outcome Score) questionnaires. Knee pain was defined as pain during the last month during most of the days. Knee OA was defined radiographically (equivalent to Kellgren and Lawrence grade ≥2) and clinically according to the American College of Rheumatology (ACR) criteria. Results: Of participants with either knee pain or knee OA or both, 7 % reported no problem for the EQ-5D-3L attributes. The corresponding proportion among references (neither knee pain nor OA) was 42 %. The participants with knee pain and OA had all HRQoL measures lower compared to those with knee pain but no OA. The ACR clinical definition of knee OA was associated with lower HRQoL than the definition based on radiographic knee OA (adjusted difference -0.08 in UK EQ-5D-3L index score). Conclusions: Applying different definitions of knee OA result in different levels of HRQoL and this is mainly explained by the knee pain experience. These differences may lead to discrepant conclusions from cost-utility analyses.
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| 38. |
- Ahmad Kiadaliri, Aliasghar, et al.
(författare)
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Socioeconomic inequalities in knee pain, knee osteoarthritis, and health-related quality of life : a population-based cohort study in southern Sweden
- 2017
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 46:2, s. 143-151
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine socioeconomic inequalities in frequent knee pain (FKP), knee osteoarthritis (OA), and associated health-related quality of life (HRQoL) in Sweden. Method: In 2007 a postal questionnaire about knee pain was sent to a random sample of 10 000 residents of Malmö, Sweden (7402 individuals responded). Subjects reporting pain with duration ≥ 4 weeks in one or both knees in the past 12 months were classified as having FKP. A random sample of 1527 subjects with and without FKP attended a clinical and radiographic knee examination and responded to generic and disease-specific HRQoL questionnaires. We used the individuals’ level of education and occupation as socioeconomic status (SES) measures, and we calculated the relative index of inequality (RII) using Poisson regression with robust standard errors adjusted for age and gender. We applied weighting to account for a possible selection bias that might arise from non-responses in the study. Results: With education, the RIIs for FKP and knee OA were 0.71 [95% confidence interval (CI) 0.61–0.84] and 0.56 (95% CI 0.34–0.93), respectively. With occupation, the corresponding figures were 0.70 (95% CI 0.60–0.82) and 0.59 (95% CI 0.37–0.94), respectively. There were socioeconomic gradients in HRQoL in favour of people with better SES. RIIs for FKP and HRQoL but not knee OA were essentially similar after additional adjustment for mediators. Conclusions: In Sweden there are socioeconomic gradients related to both FKP and knee OA as well as HRQoL in favour of people with better SES. SES should be taken into account in health resource allocation pertaining to knee-related disorders.
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| 39. |
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| 40. |
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| 41. |
- Berg, B., et al.
(författare)
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Development of osteoarthritis in patients with degenerative meniscal tears treated with exercise therapy or surgery : a randomized controlled trial
- 2020
-
Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:7, s. 897-906
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate progression of individual radiographic features 5 years following exercise therapy or arthroscopic partial meniscectomy as treatment for degenerative meniscal tear. Design: Randomized controlled trial including 140 adults, aged 35–60 years, with a magnetic resonance image verified degenerative meniscal tear, and 96% without definite radiographic knee osteoarthritis. Participants were randomized to either 12-weeks of supervised exercise therapy or arthroscopic partial meniscectomy. The primary outcome was between-group difference in progression of tibiofemoral joint space narrowing and marginal osteophytes at 5 years, assessed semi-quantitatively by the OARSI atlas. Secondary outcomes included incidence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis, medial tibiofemoral fixed joint space width (quantitatively assessed), and patient-reported outcome measures. Statistical analyses were performed using a full analysis set. Per protocol and as treated analysis were also performed. Results: The risk ratios (95% CI) for progression of semi-quantitatively assessed joint space narrowing and medial and lateral osteophytes for the surgery group were 0.89 (0.55–1.44), 1.15 (0.79–1.68) and 0.77 (0.42–1.42), respectively, compared to the exercise therapy group. In secondary outcomes (full-set analysis) no statistically significant between-group differences were found. Conclusion: The study was inconclusive with respect to potential differences in progression of individual radiographic features after surgical and non-surgical treatment for degenerative meniscal tear. Further, we found no strong evidence in support of differences in development of incident radiographic knee osteoarthritis or patient-reported outcomes between exercise therapy and arthroscopic partial meniscectomy.
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| 42. |
- Boza-Serrano, Antonio, et al.
(författare)
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Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease
- 2019
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 251-273
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer’s disease) mice and found specifically expressed in microglia associated with Aβ plaques. Single-nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aβ. Gal3 deletion decreased the Aβ burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aβ aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2–DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD.
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| 43. |
- Brantsaeter, A. L., et al.
(författare)
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Maternal intake of seafood and supplementary long chain n-3 poly-unsaturated fatty acids and preterm delivery
- 2017
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm delivery increases the risk of neonatal morbidity and mortality. Studies suggest that maternal diet may affect the prevalence of preterm delivery. The aim of this study was to assess whether maternal intakes of seafood and marine long chain n-3 polyunsaturated fatty acids (LCn-3PUFA) from supplements were associated with preterm delivery. Methods: The study population included 67,007 women from the Norwegian Mother and Child Cohort Study. Maternal food and supplement intakes were assessed by a validated self-reported food frequency questionnaire in mid-pregnancy. Information about gestational duration was obtained from the Medical Birth Registry of Norway. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between total seafood, lean fish, fatty fish, and LCn-3PUFA intakes and preterm delivery. Preterm was defined as any onset of delivery before gestational week 37, and as spontaneous or iatrogenic deliveries and as preterm delivery at early, moderate, and late preterm gestations. Results: Lean fish constituted 56%, fatty fish 34% and shellfish 10% of seafood intake. Any intake of seafood above no/rare intake (> 5 g/d) was associated with lower prevalence of preterm delivery. Adjusted HRs were 0.76 (CI: 0.66, 0.88) for 1-2 servings/week (20-40 g/d), 0.72 (CI: 0.62, 0.83) for 2-3 servings/week (40-60 g/d), and 0.72 (CI: 0.61, 0. 85) for >= 3 servings/week (>60 g/d), p-trend <0.001. The association was seen for lean fish (p-trend: 0.005) but not for fatty fish (p-trend: 0.411). The intake of supplementary LCn-3PUFA was associated only with lower prevalence of early preterm delivery (before 32 gestational weeks), while increasing intake of LCn-3PUFA from food was associated with lower prevalence of overall preterm delivery (p-trend: 0.002). Any seafood intake above no/rare was associated with lower prevalence of both spontaneous and iatrogenic preterm delivery, and with lower prevalence of late preterm delivery. Conclusions: Any intake of seafood above no/rare consumption was associated with lower prevalence of preterm delivery. The association was stronger for lean than for fatty fish. Intake of supplementary LCn-3PUFA was associated only with early preterm delivery. The findings corroborate the current advice to include fish and seafood as part of a balanced diet during pregnancy.
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| 44. |
- Burguillos Garcia, Miguel, et al.
(författare)
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Apoptosis-inducing factor mediates dopaminergic cell death in response to lps-induced inflammatory stimulus Evidence in Parkinson's disease patients.
- 2011
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 41, s. 177-188
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Tidskriftsartikel (refereegranskat)abstract
- We show that intranigral lipopolysaccharide (LPS) injection, which provokes specific degeneration of DA neurons, induced caspase-3 activation in the rat ventral mesencephalon, which was mostly associated with glial cells. In contrast, nigral DA neurons exhibited AIF nuclear translocation in response to LPS. A significant decrease of the Bcl-2/Bax ratio in nigral tissue after LPS injection was observed. We next developed an in vitro co-culture system with the microglial BV2 and the DA neuronal MN9D murine cell lines. The silencing of caspase-3 or AIF by small interfering RNAs exclusively in the DA MN9D cells demonstrated the key role of AIF in the LPS-induced death of DA cells. In vivo chemical inhibition of caspases and poly(ADP-ribose)polymerase-1, an upstream regulator of AIF release and calpain, proved the central role of the AIF-dependent pathway in LPS-induced nigral DA cell death. We also observed nuclear translocation of AIF in the ventral mesencephalon of Parkinson's disease subjects.
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| 45. |
- Burguillos Garcia, Miguel, et al.
(författare)
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Caspase signalling controls microglia activation and neurotoxicity.
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 472, s. 214-319
-
Tidskriftsartikel (refereegranskat)abstract
- Activation of microglia and inflammation-mediated neurotoxicity are suggested to play a decisive role in the pathogenesis of several neurodegenerative disorders. Activated microglia release pro-inflammatory factors that may be neurotoxic. Here we show that the orderly activation of caspase-8 and caspase-3/7, known executioners of apoptotic cell death, regulate microglia activation through a protein kinase C (PKC)-δ-dependent pathway. We find that stimulation of microglia with various inflammogens activates caspase-8 and caspase-3/7 in microglia without triggering cell death in vitro and in vivo. Knockdown or chemical inhibition of each of these caspases hindered microglia activation and consequently reduced neurotoxicity. We observe that these caspases are activated in microglia in the ventral mesencephalon of Parkinson's disease (PD) and the frontal cortex of individuals with Alzheimer's disease (AD). Taken together, we show that caspase-8 and caspase-3/7 are involved in regulating microglia activation. We conclude that inhibition of these caspases could be neuroprotective by targeting the microglia rather than the neurons themselves.
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| 46. |
- Clapham, Eric, et al.
(författare)
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Revisiting the Past and Settling the Score:Index Revision for House Price Derivatives
- 2006
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Ingår i: Real Estate Economics. - : Wiley. - 1080-8620 .- 1540-6229. ; 34:2, s. 275-302
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Tidskriftsartikel (refereegranskat)abstract
- This paper examines index revision in measuring the prices for owner-occupied housing. We consider the context of equity insurance and the settlement of futures contracts. In addition to other desirable characteristics for aggregate price indexes, their usefulness in these contexts requires stability as they are revised. Methods that are subject to substantial or complex revision raise questions about the viability of derivatives markets. Of course, all indexes are subject to revision as the result of new information. Nevertheless, we find that the most-widely used house price indexes are not equally exposed to volatility in revision. Hedonic indexes appear to be substantially more stable than repeat-sales indexes and are less prone to substantial revision in the light of new information. Moreover, we find that the repeat-sales indexes are subject to systematic downward revision. We analyze alternative settlement procedures and contracts to mitigate the impact of revision associated with repeat sale indexes.
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| 47. |
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| 48. |
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| 49. |
- Daugaard, C. L., et al.
(författare)
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The effects of weight loss on imaging outcomes in osteoarthritis of the hip or knee in people who are overweight or obese : a systematic review
- 2020
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:1, s. 10-21
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Forskningsöversikt (refereegranskat)abstract
- Objective: To evaluate the structural effects of weight loss on hip or knee osteoarthritis (OA) and to summarize which structural joint pathologies have been examined and the evidence for the outcome measurement instruments applied. Design: Based on a pre-specified protocol (available: PROSPERO CRD42017065263), we conducted a systematic search of the bibliographic databases, Medline, Embase and Web of Science identifying longitudinal articles reporting the effects of weight loss on structural imaging outcomes in OA of the hip or knee in people who are overweight or obese. Results: From 1625 potentially eligible records, 14 articles (from 6 cohorts) were included. 2 cohorts were derived from RCTs. Evaluated pathologies were: articular cartilage (n = 7), joint space width (n = 3), bone marrow lesions (n = 5), synovitis (n = 2), effusion (n = 1), meniscus (n = 3), bone marrow density (n = 1) and infrapatellar fat pad (IPFP; n = 2). Cartilage showed conflicting results when evaluating cartilage thickness by direct thickness measurements. Compositional dGEMRIC and T2 mapping measures in early knee OA showed trends towards reduced cartilage degeneration. Joint space width on conventional radiographs showed no change. Weight loss reduced the size of the IPFP. Synovitis and effusion were not affected. Following weight loss DXA showed bone loss at the hip. Conclusion: We did not find consistent evidence of the effects of weight loss on OA structural pathology in people who are overweight or obese. There is a need to achieve consensus on which structural pathologies and measurements to apply in weight loss and OA research.
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| 50. |
- Dell'Isola, Andrea, et al.
(författare)
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The coexistence of diabetes, hypertension and obesity is associated with worse pain outcomes following exercise for osteoarthritis: A cohort study on 80,893 patients
- 2024
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Ingår i: Osteoarthritis and Cartilage. - 1063-4584 .- 1522-9653.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To investigate how the co-occurrence of diabetes, hypertension and overweight/obesity is associated with pain following an exercise intervention for knee and hip osteoarthritis (OA).Methods Register-based cohort study. We included people from the Swedish Osteoarthritis Register who underwent education and exercise for knee or hip OA. Diabetes and hypertension were defined using medical records and dispensation of medication. Body Mass Index (BMI) was used to identify people with overweight (≥25 to <30), and obesity (≥30). We used linear mixed-effect models with patients nested into clinics to estimate the associations between the exposures and pain (Numeric Rating Scale 0–10), adjusting for age, sex, education, and physical activity.Results We analysed 80,893 patients with knee or hip OA. The accumulation of metabolic conditions was associated with worse pain at baseline and follow-ups. When obesity, hypertension and diabetes coexisted, patients treated for knee OA reported more pain at baseline (adjusted mean pain difference 0.9 [95 %CI: 0.8; 1.0]), 3 months (1.0 [0.9; 1.1]) and 12 months (1.3 [1.1; 1.4]) compared to those without any of the conditions. Similar results were observed for patients treated for hip OA when obesity, hypertension and diabetes coexisted (baseline (0.7 [0.5; 0.8], 3 (0.8[0.6; 1.0]) and 12 months (1.1[0.8; 1.3]).Conclusions When diabetes, hypertension and obesity coexist with OA, patients not only experience heightened baseline pain compared to metabolically healthy individuals, but the disparity increases after an education and exercise intervention suggesting that a one-size-fits-all approach may be inadequate in addressing the complex interplay between metabolic health and OA.
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