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Sökning: WFRF:(Schober A)

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  • Cossarizza, A., et al. (författare)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Tidskriftsartikel (refereegranskat)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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  • Abele, H., et al. (författare)
  • Particle physics at the European Spallation Source
  • 2023
  • Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84
  • Forskningsöversikt (refereegranskat)abstract
    • Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
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  • Santoro, V., et al. (författare)
  • The HighNESS Project at the European Spallation Source : Current Status and Future Perspectives
  • 2024
  • Ingår i: Nuclear science and engineering. - 0029-5639 .- 1943-748X. ; 198:1, s. 31-63
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Spallation Source (ESS), presently under construction in Lund, Sweden, is a multidisciplinary international laboratory that, once completed at full specifications, will operate the world's most powerful pulsed neutron source. Supported by a 3 M Euro Research and Innovation Action within the European Union Horizon 2020 program, a design study (HighNESS) is now underway to develop a second neutron source located below the spallation target. Compared to the first source, which is located above the spallation target and designed for high cold and thermal brightness, the new source is being optimized to deliver higher intensity and a shift to longer wavelengths in the spectral regions of cold neutrons (CNs) (2 to 20 & Aring;), very cold neutrons (VCNs) (10 to 120 & Aring;), and ultracold neutrons (UCNs) (> 500 & Aring;). The second source consists of a large liquid deuterium moderator to deliver CNs and serve secondary VCN and UCN sources, for which different options are under study. These new sources will boost several areas of condensed matter research and will provide unique opportunities in fundamental physics. The HighNESS project is now entering its last year, and we are working toward the Conceptual Design Report of the ESS upgrade. In this paper, results obtained in the first 2 years, ongoing developments, and future perspectives are described.
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  • Bölling, T, et al. (författare)
  • Development of Curative Therapies for Ewing Sarcomas by Interdisciplinary Cooperative Groups in Europe.
  • 2015
  • Ingår i: Klinische Pädiatrie. - : Georg Thieme Verlag KG. - 1439-3824 .- 0300-8630. ; 227:3, s. 108-115
  • Forskningsöversikt (refereegranskat)abstract
    • Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival.
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  • McKnight, J. A., et al. (författare)
  • Glycaemic control of Type1 diabetes in clinical practice early in the 21st century: an international comparison
  • 2015
  • Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071. ; 32:8, s. 1036-1050
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsImproving glycaemic control in people with Type1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type1 diabetes using data gathered in regional or national registries. MethodsData were obtained for children and/or adults with Type1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173880. Proportions with HbA(1c) <58mmol/mol (<7.5%) and 75mmol/mol (9.0%) were compared by age and sex. ResultsData were available for 324501 people. The proportions with HbA(1c) 58mmol/mol (<7.5%) varied from 15.7% to 46.4% among 44058 people aged <15years, from 8.9% to 49.5% among 50766 people aged 15-24years and from 20.5% to 53.6% among 229677 people aged 25years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. ConclusionThese results suggest that there are substantial variations in glycaemic control among people with Type1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults. We present HbA(1c) data from registries in 19 different countries describing control in 324501 people with Type1 diabetes, across all age groups. These data are the best representation of diabetes care available and therefore describe the state of the art'. We show clearly that Type1 diabetes control is not as good as suggested in guidelines, but that some healthcare systems appear to result in better control than others. These data present a challenge to diabetes services. Leaders in diabetes units/service can compare their local data to our data and encourage improvement.
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  • Siibak, Triinu, et al. (författare)
  • A multi-systemic mitochondrial disorder due to a dominant p.Y955H disease variant in DNA polymerase gamma
  • 2017
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 26:13, s. 2515-2525
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutations in the mitochondrial DNA polymerase, POLG, are associated with a variety of clinical presentations, ranging from early onset fatal brain disease in Alpers syndrome to chronic progressive external ophthalmoplegia. The majority of mutations are linked with disturbances of mitochondrial DNA (mtDNA) integrity and maintenance. On a molecular level, depending on their location within the enzyme, mutations either lead to mtDNA depletion or the accumulation of multiple mtDNA deletions, and in some cases these molecular changes can be correlated to the clinical presentation. We identified a patient with a dominant p.Y955H mutation in POLG, presenting with a severe, early-onset multi-systemic mitochondrial disease with bilateral sensorineural hearing loss, cataract, myopathy, and liver failure. Using a combination of disease models of Drosophila melanogaster and in vitro biochemistry analysis, we compare the molecular consequences of the p.Y955H mutation to the well-documented p.Y955C mutation. We demonstrate that both mutations affect mtDNA replication and display a dominant negative effect, with the p.Y955H allele resulting in a more severe polymerase dysfunction.
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  • Cardwell, C R, et al. (författare)
  • Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data
  • 2010
  • Ingår i: DIABETOLOGIA. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 53:4, s. 641-651
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p = 0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p = 0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p = 0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.
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  • Engvall, M, et al. (författare)
  • Case Report: A Novel Mutation in the Mitochondrial MT-ND5 Gene Is Associated With Leber Hereditary Optic Neuropathy (LHON)
  • 2021
  • Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 12, s. 652590-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Leber hereditary optic neuropathy (LHON) is a mitochondrial disease causing severe bilateral visual loss, typically in young adults. The disorder is commonly caused by one of three primary point mutations in mitochondrial DNA, but a number of other rare mutations causing or associated with the clinical syndrome of LHON have been reported. The mutations in LHON are almost exclusively located in genes encoding subunits of complex I in the mitochondrial respiratory chain. Here we report two patients, a mother and her son, with the typical LHON phenotype. Genetic investigations for the three common mutations were negative, instead we found a new and previously unreported mutation in mitochondrial DNA. This homoplasmic mutation, m.13345G&gt;A, is located in the MT-ND5 gene, encoding a core subunit in complex I in the mitochondrial respiratory chain. Investigation of the patients mitochondrial respiratory chain in muscle found a mild defect in the combined activity of complex I+III. In the literature six other mutations in the MT-ND5 gene have been associated with LHON and by this report a new putative mutation in the MT-ND5 can be added.
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  • Park, Seung Hyun, et al. (författare)
  • Nonpharmaceutical interventions reduce the incidence and mortality of COVID-19: A study based on the survey from the International COVID-19 Research Network (ICRN)
  • 2023
  • Ingår i: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 95:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)," caused a highly contagious disease called coronavirus disease 2019 (COVID-19). It has severely damaged the worlds most developed countries and has turned into a major threat for low- and middle-income countries. Since its emergence in late 2019, medical interventions have been substantial, and most countries relied on public health measures collectively known as nonpharmaceutical interventions (NPIs). We aimed to centralize the accumulative knowledge of NPIs against COVID-19 for each country under one worldwide consortium. International COVID-19 Research Network collaborators developed a cross-sectional online survey to assess the implications of NPIs and sanitary supply on the incidence and mortality of COVID-19. The survey was conducted between January 1 and February 1, 2021, and participants from 92 countries/territories completed it. The association between NPIs, sanitation supplies, and incidence and mortality were examined by multivariate regression, with the log-transformed value of population as an offset value. The majority of countries/territories applied several preventive strategies, including social distancing (100.0%), quarantine (100.0%), isolation (98.9%), and school closure (97.8%). Individual-level preventive measures such as personal hygiene (100.0%) and wearing facial masks (94.6% at hospitals; 93.5% at mass transportation; 91.3% in mass gathering facilities) were also frequently applied. Quarantine at a designated place was negatively associated with incidence and mortality compared to home quarantine. Isolation at a designated place was also associated with reduced mortality compared to home isolation. Recommendations to use sanitizer for personal hygiene reduced incidence compared to the recommendation to use soap. Deprivation of masks was associated with increased incidence. Higher incidence and mortality were found in countries/territories with higher economic levels. Mask deprivation was pervasive regardless of economic level. NPIs against COVID-19 such as using sanitizer, quarantine, and isolation can decrease the incidence and mortality of COVID-19.
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  • Abou Ghayda, Ramy, et al. (författare)
  • The global case fatality rate of coronavirus disease 2019 by continents and national income: A meta-analysis
  • 2022
  • Ingår i: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 94:6, s. 2402-2413
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study is to provide a more accurate representation of COVID-19s case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.
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  • Clemente, P, et al. (författare)
  • ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing
  • 2022
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 5750-
  • Tidskriftsartikel (refereegranskat)abstract
    • Canonical RNA processing in mammalian mitochondria is defined by tRNAs acting as recognition sites for nucleases to release flanking transcripts. The relevant factors, their structures, and mechanism are well described, but not all mitochondrial transcripts are punctuated by tRNAs, and their mode of processing has remained unsolved. Using Drosophila and mouse models, we demonstrate that non-canonical processing results in the formation of 3′ phosphates, and that phosphatase activity by the carbon catabolite repressor 4 domain-containing family member ANGEL2 is required for their hydrolysis. Furthermore, our data suggest that members of the FAST kinase domain-containing protein family are responsible for these 3′ phosphates. Our results therefore propose a mechanism for non-canonical RNA processing in metazoan mitochondria, by identifying the role of ANGEL2.
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25.
  • Euchner, H., et al. (författare)
  • Anomalous vibrational dynamics in the Mg(2)Zn(11) phase
  • 2011
  • Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 83:14, s. 144202-
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a combined experimental and theoretical study of the structure and the lattice dynamics in the complex metallic alloy Mg(2)Zn(11), by means of neutron and x-ray scattering, as well as ab initio and empirical potential calculations. Mg(2)Zn(11) can be seen as an intermediate step in structural complexity between the simple Laves-phase MgZn(2) on one side, and the complex 1/1 approximants and quasicrystals ZnMgAl and Zn(Mg)Sc on the other. The structure can be described as a cubic packing of a triacontahedron whose center is partially occupied by a Zn atom. This partially occupied site turned out to play a major role in understanding the lattice dynamics. Data from inelastic neutron scattering evidence a Van Hove singularity in the vibrational spectrum of Mg(2)Zn(11) for an energy as low as 4.5 meV, which is a unique feature for a nearly-close-packed metallic alloy. This corresponds to a gap opening at the Brillouin zone boundary and an interaction between a low-lying optical branch and an acoustic one, as could be deduced from the dispersion relation measured by inelastic x-ray scattering. Second, the measured phonon density of states exhibits many maxima, indicating strong mode interactions across the whole energy range. The origin of the low-energy modes in Mg(2)Zn(11) and other features of the vibrational spectra are studied, using both ab initio and empirical potential calculations. A detailed analysis of vibrational eigenmodes is presented, linking features in the vibrational spectrum to atomic motions within structural building blocks.
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26.
  • Euchner, H., et al. (författare)
  • Anomalous vibrational dynamics in the Mg2Zn11 phase
  • 2011
  • Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 83:14, s. 144202-
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a combined experimental and theoretical study of the structure and the lattice dynamics in the complex metallic alloy Mg2Zn11, by means of neutron and x-ray scattering, as well as ab initio and empirical potential calculations. Mg2Zn11 can be seen as an intermediate step in structural complexity between the simple Laves-phase MgZn2 on one side, and the complex 1/1 approximants and quasicrystals ZnMgAl and Zn(Mg)Sc on the other. The structure can be described as a cubic packing of a triacontahedron whose center is partially occupied by a Zn atom. This partially occupied site turned out to play a major role in understanding the lattice dynamics. Data from inelastic neutron scattering evidence a Van Hove singularity in the vibrational spectrum of Mg2Zn11 for an energy as low as 4.5 meV, which is a unique feature for a nearly-close-packed metallic alloy. This corresponds to a gap opening at the Brillouin zone boundary and an interaction between a low-lying optical branch and an acoustic one, as could be deduced from the dispersion relation measured by inelastic x-ray scattering. Second, the measured phonon density of states exhibits many maxima, indicating strong mode interactions across the whole energy range. The origin of the low-energy modes in Mg2Zn11 and other features of the vibrational spectra are studied, using both ab initio and empirical potential calculations. A detailed analysis of vibrational eigenmodes is presented, linking features in the vibrational spectrum to atomic motions within structural building blocks.
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  • Patterson, C. C., et al. (författare)
  • Trends in childhood type 1 diabetes incidence in Europe during 1989-2008 : evidence of non-uniformity over time in rates of increase
  • 2012
  • Ingår i: Diabetologia. - : Springer-Verlag New York. - 0012-186X .- 1432-0428. ; 55:8, s. 2142-2147
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to describe 20-year incidence trends for childhood type 1 diabetes in 23 EURODIAB centres and compare rates of increase in the first (1989-1998) and second (1999-2008) halves of the period. All registers operate in geographically defined regions and are based on a clinical diagnosis. Completeness of registration is assessed by capture-recapture methodology. Twenty-three centres in 19 countries registered 49,969 new cases of type 1 diabetes in individuals diagnosed before their 15th birthday during the period studied. Ascertainment exceeded 90% in most registers. During the 20-year period, all but one register showed statistically significant changes in incidence, with rates universally increasing. When estimated separately for the first and second halves of the period, the median rates of increase were similar: 3.4% per annum and 3.3% per annum, respectively. However, rates of increase differed significantly between the first half and the second half for nine of the 21 registers with adequate coverage of both periods; five registers showed significantly higher rates of increase in the first half, and four significantly higher rates in the second half. The incidence rate of childhood type 1 diabetes continues to rise across Europe by an average of approximately 3-4% per annum, but the increase is not necessarily uniform, showing periods of less rapid and more rapid increase in incidence in some registers. This pattern of change suggests that important risk exposures differ over time in different European countries. Further time trend analysis and comparison of the patterns in defined regions is warranted.
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31.
  • Patterson, Cc, et al. (författare)
  • Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 European centers during 1989-2008 : little short-term influence of sunshine hours or average temperature
  • 2015
  • Ingår i: Pediatric Diabetes. - : Wiley-Blackwell. - 1399-543X .- 1399-5448. ; 16:8, s. 573-580
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The month of diagnosis in childhood type 1 diabetes shows seasonal variation.OBJECTIVE: We describe the pattern and investigate if year-to-year irregularities are associated with meteorological factors using data from 50 000 children diagnosed under the age of 15 yr in 23 population-based European registries during 1989-2008.METHODS: Tests for seasonal variation in monthly counts aggregated over the 20 yr period were performed. Time series regression was used to investigate if sunshine hour and average temperature data were predictive of the 240 monthly diagnosis counts after taking account of seasonality and long term trends.RESULTS: Significant sinusoidal pattern was evident in all but two small centers with peaks in November to February and relative amplitudes ranging from ±11 to ±38% (median ±17%). However, most centers showed significant departures from a sinusoidal pattern. Pooling results over centers, there was significant seasonal variation in each age-group at diagnosis, with least seasonal variation in those under 5 yr. Boys showed greater seasonal variation than girls, particularly those aged 10-14 yr. There were no differences in seasonal pattern between four 5-yr sub-periods. Departures from the sinusoidal trend in monthly diagnoses in the period were significantly associated with deviations from the norm in average temperature (0.8% reduction in diagnoses per 1 °C excess) but not with sunshine hours.CONCLUSIONS: Seasonality was consistently apparent throughout the period in all age-groups and both sexes, but girls and the under 5 s showed less marked variation. Neither sunshine hour nor average temperature data contributed in any substantial way to explaining departures from the sinusoidal pattern.
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  • van Rijswijk, Merlijn, et al. (författare)
  • The future of metabolomics in ELIXIR.
  • 2017
  • Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolomics, the youngest of the major omics technologies, is supported by an active community of researchers and infrastructure developers across Europe. To coordinate and focus efforts around infrastructure building for metabolomics within Europe, a workshop on the "Future of metabolomics in ELIXIR" was organised at Frankfurt Airport in Germany. This one-day strategic workshop involved representatives of ELIXIR Nodes, members of the PhenoMeNal consortium developing an e-infrastructure that supports workflow-based metabolomics analysis pipelines, and experts from the international metabolomics community. The workshop established metabolite identification as the critical area, where a maximal impact of computational metabolomics and data management on other fields could be achieved. In particular, the existing four ELIXIR Use Cases, where the metabolomics community - both industry and academia - would benefit most, and which could be exhaustively mapped onto the current five ELIXIR Platforms were discussed. This opinion article is a call for support for a new ELIXIR metabolomics Use Case, which aligns with and complements the existing and planned ELIXIR Platforms and Use Cases.
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36.
  • Bals, Robert, et al. (författare)
  • Electronic cigarettes : a task force report from the European Respiratory Society
  • 2019
  • Ingår i: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 53:2
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a marked increase in the development and use of electronic nicotine delivery systems or electronic cigarettes (ECIGs). This statement covers electronic cigarettes (ECIGs), defined as "electrical devices that generate an aerosol from a liquid" and thus excludes devices that contain tobacco. Database searches identified published articles that were used to summarise the current knowledge on the epidemiology of ECIG use; their ingredients and accompanied health effects; second-hand exposure; use of ECIGs for smoking cessation; behavioural aspects of ECIGs and social impact; in vitro and animal studies; and user perspectives. ECIG aerosol contains potentially toxic chemicals. As compared to conventional cigarettes, these are fewer and generally in lower concentrations. Second-hand exposures to ECIG chemicals may represent a potential risk, especially to vulnerable populations. There is not enough scientific evidence to support ECIGs as an aid to smoking cessation due to a lack of controlled trials, including those that compare ECIGs with licenced stop-smoking treatments. So far, there are conflicting data that use of ECIGs results in a renormalisation of smoking behaviour or for the gateway hypothesis. Experiments in cell cultures and animal studies show that ECIGs can have multiple negative effects. The long-term effects of ECIG use are unknown, and there is therefore no evidence that ECIGs are safer than tobacco in the long term. Based on current knowledge, negative health effects cannot be ruled out.
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  • Cardwell, Chris R, et al. (författare)
  • Birth order and childhood type 1 diabetes risk: a pooled analysis of 31 observational studies
  • 2011
  • Ingår i: INTERNATIONAL JOURNAL OF EPIDEMIOLOGY. - : OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND. - 0300-5771 .- 1464-3685. ; 40:2, s. 363-374
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. Methods Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. Results Data were available for 6 cohort and 25 case-control studies, including 11 955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second- or later born children became apparent [fully adjusted OR = 0.90 95% confidence interval (CI) 0.83-0.98; P = 0.02] but this association varied markedly between studies (I-2 = 67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children andlt; 5 years of age (n = 25 studies, maternal age adjusted OR = 0.84 95% CI 0.75, 0.93; I-2 = 23%). Conclusion Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged andlt; 5 years. This finding could reflect increased exposure to infections in early life in later born children.
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  • Cardwell, Chris R, et al. (författare)
  • Maternal Age at Birth and Childhood Type 1 Diabetes: A Pooled Analysis of 30 Observational Studies
  • 2010
  • Ingår i: DIABETES. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:2, s. 486-494
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE-The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders. RESEARCH DESIGN AND METHODS-Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies. RESULTS-Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2-9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I-2 = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. CONCLUSIONS-There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.
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  • Clerckx, Bruno, et al. (författare)
  • Is NOMA Efficient in Multi-Antenna Networks? : A Critical Look at Next Generation Multiple Access Techniques
  • 2021
  • Ingår i: IEEE Open Journal of the Communications Society. - : Institute of Electrical and Electronics Engineers (IEEE). - 2644-125X. ; 2, s. 1310-1343
  • Tidskriftsartikel (refereegranskat)abstract
    • In the past few years, a large body of literature has been created on downlink Non-Orthogonal Multiple Access (NOMA), employing superposition coding and Successive Interference Cancellation (SIC), in multi-antenna wireless networks. Furthermore, the benefits of NOMA over Orthogonal Multiple Access (OMA) have been highlighted. In this paper, we take a critical and fresh look at the downlink Next Generation Multiple Access (NGMA) literature. Instead of contrasting NOMA with OMA, we contrast NOMA with two other multiple access baselines. The first is conventional Multi-User Linear Precoding (MU-LP), as used in Space-Division Multiple Access (SDMA) and multi-user Multiple-Input Multiple-Output (MIMO) in 4G and 5G. The second, called Rate-Splitting Multiple Access (RSMA), is based on multi-antenna Rate-Splitting (RS). It is also a non-orthogonal transmission strategy relying on SIC developed in the past few years in parallel and independently from NOMA. We show that there is some confusion about the benefits of NOMA, and we dispel the associated misconceptions. First, we highlight why NOMA is inefficient in multi-antenna settings based on basic multiplexing gain analysis. We stress that the issue lies in how the NOMA literature, originally developed for single-antenna setups, has been hastily applied to multi-antenna setups, resulting in a misuse of spatial dimensions and therefore loss in multiplexing gains and rate. Second, we show that NOMA incurs a severe multiplexing gain loss despite an increased receiver complexity due to an inefficient use of SIC receivers. Third, we emphasize that much of the merits of NOMA are due to the constant comparison to OMA instead of comparing it to MU-LP and RS baselines. We then expose the pivotal design constraint that multi-antenna NOMA requires one user to fully decode the messages of the other users. This design constraint is responsible for the multiplexing gain erosion, rate and spectral efficiency loss, ineffectiveness to serve a large number of users, and inefficient use of SIC receivers in multi-antenna settings. Our analysis and simulation results confirm that NOMA should not be applied blindly to multi-antenna settings, highlight the scenarios where MU-LP outperforms NOMA and vice versa, and demonstrate the inefficiency, performance loss, and complexity disadvantages of NOMA compared to RSMA. The first takeaway message is that, while NOMA is suited for single-antenna settings (as originally intended), it is not efficient in most multi-antenna deployments. The second takeaway message is that another non-orthogonal transmission framework, based on RSMA, exists which fully exploits the multiplexing gain and the benefits of SIC to boost the rate and the number of users to serve in multi-antenna settings and outperforms both NOMA and MU-LP. Indeed, RSMA achieves higher multiplexing gains and rates, serves a larger number of users, is more robust to user deployments, network loads and inaccurate channel state information and has a lower receiver complexity than NOMA. Consequently, RSMA is a promising technology for NGMA and future networks such as 6G and beyond.
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41.
  • Coomans, Emma M., et al. (författare)
  • In vivo tau pathology is associated with synaptic loss and altered synaptic function
  • 2021
  • Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([18F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease. Methods: Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [18F]flortaucipir PET, dynamic 60-min [11C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [18F]flortaucipir- and [11C]UCB-J-specific binding (binding potential, BPND) and MEG spectral measures (relative delta, theta and alpha power; broadband power; and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [18F]flortaucipir BPND, [11C]UCB-J BPND and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models. Results: Across subjects, higher regional [18F]flortaucipir uptake was associated with lower [11C]UCB-J uptake. Within subjects, the association between [11C]UCB-J and [18F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [18F]flortaucipir and lower [11C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe. Conclusions: These results indicate that in Alzheimer’s disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction.
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42.
  • Dal Bello, F., et al. (författare)
  • Improvement of the quality and shelf life of wheat bread by fermentation with the antifungal strain Lactobacillus plantarum FST 1.7
  • 2007
  • Ingår i: Journal of Cereal Science. - London, United Kingdom : Elsevier. - 0733-5210 .- 1095-9963. ; 45:3, s. 309-318
  • Tidskriftsartikel (refereegranskat)abstract
    • Lactobacillus plantarum FST 1.7 was screened for in vitro antimicrobial activity and was shown to be active against spoilage moulds and bacteria. Isolation of antimicrobial compounds from cell-free supernatant identified lactic acid, phenyllactic acid and the two cyclic dipeptides cyclo ((L)-Leu-(L)-Pro) and cyclo ((L)-Phe-(L)-Pro) as the major components responsible for this activity. L. plantarum FST 1.7 was tested for the ability to produce the antifungal compounds during sourdough fermentation and to produce bread of good quality and increased shelf-life. A rheofermentometer was used to examine the gaseous release and development characteristics of the dough. A range of parameters was determined including pH, TTA and specific loaf volume. The results were compared with those obtained using Lactobacillus sanfranciscensis, a chemically acidified and a non-acidified dough. The quality of sourdough and bread produced using L. plantarum FST 1.7 was comparable to that obtained using common sourdough starters, e.g. L. sanfranciscensis. Sourdoughs and breads were evaluated for the ability to retard growth of Fusarium culmorum and Fusarium graminearum two fungi found on breads. Sourdough and bread produced with strain FST 1.7 showed consistent ability to retard the growth of both Fusarium species, thus indicating that L. plantarum FST 1.7 has also the potential to improve the shelf-life of wheat bread.
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43.
  • Emami Khoonsari, Payam, et al. (författare)
  • Interoperable and scalable data analysis with microservices : Applications in metabolomics
  • 2019
  • Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 35:19, s. 3752-3760
  • Tidskriftsartikel (refereegranskat)abstract
    • MotivationDeveloping a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed using the Kubernetes container orchestrator.ResultsWe developed a Virtual Research Environment (VRE) which facilitates rapid integration of new tools and developing scalable and interoperable workflows for performing metabolomics data analysis. The environment can be launched on-demand on cloud resources and desktop computers. IT-expertise requirements on the user side are kept to a minimum, and workflows can be re-used effortlessly by any novice user. We validate our method in the field of metabolomics on two mass spectrometry, one nuclear magnetic resonance spectroscopy and one fluxomics study. We showed that the method scales dynamically with increasing availability of computational resources. We demonstrated that the method facilitates interoperability using integration of the major software suites resulting in a turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, statistics and identification. Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative science.
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46.
  • Javed, Muhammad Ahsan, et al. (författare)
  • Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe
  • 2019
  • Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 19:1, s. 97-104
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe.METHODS: A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors.RESULTS: Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4-12.6), NAB+GEM 7.9 months (95%CI 6.2-10.0), other combinations 8.5 months (95%CI 7.7-9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4-5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1-3) with poor prognosis.CONCLUSION: Gemcitabine monotherapy was predominantly used in 2012-2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.
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47.
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48.
  • Le, Nha, et al. (författare)
  • Real-world clinical practice of intensified chemotherapies for metastatic pancreatic cancer : results from a Pan-European questionnaire study
  • 2016
  • Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 94:4, s. 222-229
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Recently, FOLFIRINOX and gemcitabine + nab-paclitaxel have been introduced as a novel intensified chemotherapy regimen for patients with metastasized pancreatic cancer. This study aims to analyze the real-world clinical practice with FOLFIRINOX and gemcitabine + nab-paclitaxel across Europe.Methods: Invitations to participate in an anonymous web-based questionnaire were sent via e-mail to 5,420 doctors in 19 European countries through the network of national gastroenterological, oncological, surgical and pancreatic societies as well as the European Pancreatic Club. The questionnaire consisted of 20 questions, 14 regarding the use of intensified chemotherapy, 4 regarding demographics of the participants, and 1 to verify the active involvement in the management of metastatic pancreatic cancer.Results: Two hundred and thirteen responses were received and 153 entries were valid for analysis. Of those, 63.4% came from an academic institution, 51% were oncologists, and 52% treated more than 25 cases per year. A majority of responses (71%) were from Italy (40%), Germany (23%), and Spain (8%). As first-line therapy, 11% used gemcitabine +/- erlotinib, 42% used FOLFIRINOX, and 47% used gemcitabine + nab-paclitaxel. Of the intensified regimens, both were applied to equal parts, but the likelihood of protocol deviation was higher when using FOLFIRINOX (p < 0.01). FOLFIRINOX was considered more toxic than gemcitabine + nab-paclitaxel (neutropenia 88 vs. 68%; polyneuropathy 42 vs. 41%; rapid deterioration 42 vs. 31%). FOLFIRINOX was rated to achieve longer survival with an acceptable quality of life (52 vs. 44%). Moreover, 57% of participants thought that gemcitabine + nab-paclitaxel should be the backbone for further clinical trials in pancreatic cancer.Conclusion: Intensified chemotherapy is widely used in pancreatic cancer patients in Europe following its recent clinical approval. Interestingly, nab-paclitaxel and FOLFIRINOX were used at comparable frequency although the latter had to be de-escalated more often.
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