| 1. |
- Bécoulet, A., et al.
(författare)
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Science and technology research and development in support to ITER and the Broader Approach at CEA
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10
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Tidskriftsartikel (refereegranskat)abstract
- In parallel to the direct contribution to the procurement phase of ITER and Broader Approach, CEA has initiated research & development programmes, accompanied by experiments together with a significant modelling effort, aimed at ensuring robust operation, plasma performance, as well as mitigating the risks of the procurement phase. This overview reports the latest progress in both fusion science and technology including many areas, namely the mitigation of superconducting magnet quenches, disruption-generated runaway electrons, edge-localized modes (ELMs), the development of imaging surveillance, and heating and current drive systems for steady-state operation. The WEST (W Environment for Steady-state Tokamaks) project, turning Tore Supra into an actively cooled W-divertor platform open to the ITER partners and industries, is presented.
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| 2. |
- Zuntini, Alexandre R., et al.
(författare)
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Phylogenomics and the rise of the angiosperms
- 2024
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Ingår i: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850
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Tidskriftsartikel (refereegranskat)abstract
- Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
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| 3. |
- Danaei, Goodarz, et al.
(författare)
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Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
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| 4. |
- Zhou, Bin, et al.
(författare)
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Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
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Ingår i: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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| 5. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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| 6. |
- Rosenling, Therese, 1980-, et al.
(författare)
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The effect of preanalytical factors on stability of the proteome and selected metabolites in cerebrospinal fluid (CSF).
- 2009
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 8:12, s. 5511-22
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Tidskriftsartikel (refereegranskat)abstract
- To standardize the use of cerebrospinal fluid (CSF) for biomarker research, a set of stability studies have been performed on porcine samples to investigate the influence of common sample handling procedures on proteins, peptides, metabolites and free amino acids. This study focuses at the effect on proteins and peptides, analyzed by applying label-free quantitation using microfluidics nanoscale liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (chipLC-MS) as well as matrix-assisted laser desorption ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FT-ICR-MS) and Orbitrap LC-MS/MS to trypsin-digested CSF samples. The factors assessed were a 30 or 120 min time delay at room temperature before storage at -80 degrees C after the collection of CSF in order to mimic potential delays in the clinic (delayed storage), storage at 4 degrees C after trypsin digestion to mimic the time that samples remain in the cooled autosampler of the analyzer, and repeated freeze-thaw cycles to mimic storage and handling procedures in the laboratory. The delayed storage factor was also analyzed by gas chromatography mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS) for changes of metabolites and free amino acids, respectively. Our results show that repeated freeze/thawing introduced changes in transthyretin peptide levels. The trypsin digested samples left at 4 degrees C in the autosampler showed a time-dependent decrease of peak areas for peptides from prostaglandin D-synthase and serotransferrin. Delayed storage of CSF led to changes in prostaglandin D-synthase derived peptides as well as to increased levels of certain amino acids and metabolites. The changes of metabolites, amino acids and proteins in the delayed storage study appear to be related to remaining white blood cells. Our recommendations are to centrifuge CSF samples immediately after collection to remove white blood cells, aliquot, and then snap-freeze the supernatant in liquid nitrogen for storage at -80 degrees C. Preferably samples should not be left in the autosampler for more than 24 h and freeze/thaw cycles should be avoided if at all possible.
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| 7. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 8. |
- Kowal, Marta, et al.
(författare)
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Reasons for Facebook Usage : Data From 46 Countries
- 2020
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Seventy-nine percent of internet users use Facebook, and on average they access Facebook eight times a day (Greenwood et al., 2016). To put these numbers into perspective, according to Clement (2019), around 30% of the world's population uses this Online Social Network (OSN) site.Despite the constantly growing body of academic research on Facebook (Chou et al., 2009; Back et al., 2010; Kaplan and Haenlein, 2010; McAndrew and Jeong, 2012; Wilson et al., 2012; Krasnova et al., 2017), there remains limited research regarding the motivation behind Facebook use across different cultures. Our main goal was to collect data from a large cross-cultural sample of Facebook users to examine the roles of sex, age, and, most importantly, cultural differences underlying Facebook use.
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| 9. |
- Rosenling, Therese, et al.
(författare)
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The Impact of Delayed Storage on the Measured Proteome and Metabolome of Human Cerebrospinal Fluid
- 2011
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 57:12, s. 1703-1711
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Because cerebrospinal fluid (CSF) is in close contact with diseased areas in neurological disorders, it is an important source of material in the search for molecular biomarkers. However, sample handling for CSF collected from patients in a clinical setting might not always be adequate for use in proteomics and metabolomics studies. METHODS: We left CSF for 0, 30, and 120 min at room temperature immediately after sample collection and centrifugation/removal of cells. After tryptic digestion at 2 laboratories by nanoLC Orbitrap-MS and chipLC QTOF-MS, CSF proteomes were analyzed. Metabolome analysis was performed at 3 laboratories by NMR, GC-MS, and LC-MS. Targeted analyses of cystatin C and albumin were performed by LC-MS/MS in the selected reaction monitoring mode. RESULTS: We did not find significant changes in the measured proteome and metabolome of CSF stored at room temperature after centrifugation, except for 2 peptides and 1 metabolite, 2,3,4-trihydrobutanoic acid, of 5780 identified peptides and 93 identified metabolites. A sensitive protein stability marker, cystatin C, was not affected. CONCLUSIONS: The measured proteome and metabolome of centrifuged, human CSF is stable at room temperature for up to 2 hours. We cannot exclude, however, that changes undetectable with our current methodology, such as denaturation or proteolysis, might occur due to sample handling conditions. The stability we observed gives laboratory personnel at the collection site sufficient time to aliquot samples before freezing and storage at -80 °C.
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| 10. |
- Abraham, Vojtech, et al.
(författare)
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Patterns in recent and Holocene pollen accumulation rates across Europe - the Pollen Monitoring Programme Database as a tool for vegetation reconstruction
- 2021
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 18:15, s. 4511-4534
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Tidskriftsartikel (refereegranskat)abstract
- The collection of modern, spatially extensive pollen data is important for the interpretation of fossil pollen assemblages and the reconstruction of past vegetation communities in space and time. Modern datasets are readily available for percentage data but lacking for pollen accumulation rates (PARs). Filling this gap has been the motivation of the pollen monitoring network, whose contributors monitored pollen deposition in modified Tauber traps for several years or decades across Europe. Here we present this monitoring dataset consisting of 351 trap locations with a total of 2742 annual samples covering the period from 1981 to 2017. This dataset shows that total PAR is influenced by forest cover and climate parameters, which determine pollen productivity and correlate with latitude. Treeless vegetation produced PAR values of at least 140 grains cm(-2) yr(-1). Tree PAR increased by at least 400 grains cm(-2) yr(-1) with each 10% increase in forest cover. Pollen traps situated beyond 200 km of the distribution of a given tree species still collect occasional pollen grains of that species. The threshold of this long-distance transport differs for individual species and is generally below 60 grains cm(-2) yr(-1). Comparisons between modern and fossil PAR from the same regions show similar values. For temperate taxa, modern analogues for fossil PARs are generally found downslope or southward of the fossil sites. While we do not find modern situations comparable to fossil PAR values of some taxa (e.g. Corylus), CO2 fertilization and land use may cause high modern PARs that are not documented in the fossil record. The modern data are now publicly available in the Neotoma Paleoecology Database and aid interpretations of fossil PAR data.
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| 11. |
- Bogo, Renata, et al.
(författare)
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The Role of Genetic Factors for Hearing Deterioration Across 20 Years : A Twin Study
- 2015
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 70:5, s. 647-653
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Tidskriftsartikel (refereegranskat)abstract
- Background. Hearing deterioration at advanced ages is associated with environmental exposures (eg, to noise and solvents) and genetic influences may also be important. Little is known about the role of genetic influences on hearing when evaluated longitudinally. We sought to investigate longitudinal hearing loss in a cohort of adult male twins to evaluate the importance of genetic and environmental factors for hearing deterioration over time. Methods. Hearing using conventional clinical audiometry was assessed in 583 male twins (128 monozygotic twin pairs and 111 dizygotic twin pairs) aged 34-79 at baseline and again two decades later. The hearing thresholds at two time points were compared at each frequency and in two different frequency regions. Genetic analyses were based on structural equation models. Bivariate Cholesky decomposition was used for longitudinal analysis. Results. The prevalence of hearing loss increased over time in better and worse ear. The hearing threshold shift was more pronounced in the high-frequency region, especially at 8000 Hz. Genetic influences were moderate (heritability: 53%-65%) for pure-tone averages at both lower and higher frequencies, and were of equal magnitude at baseline and follow-up. In contrast, environmental influences were of substantial importance (55%-88%) for rate of change of the hearing threshold over the 18-year period. Conclusions. Genetic factors are of considerable importance for level of hearing acuity, but environmental factors are more important for rate of change over an 18-year period.
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| 12. |
- Bolognesi, B, et al.
(författare)
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The N-terminus of amyloid-beta plays a crucial role in its aggregation and toxicity
- 2010
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Ingår i: The FEBS Journal. - : Wiley-Blackwell. - 1742-464X .- 1742-4658. ; 277:Suppl. 1, s. 79-80
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The aggregation of Amyloid Beta (Aß) peptide into insolubleamyloid fibrils that deposit in the brain is one of the primarypathogenic events in Alzheimer’s disease. We have previouslyshown, using a Drosophila model of Aß toxicity, that the N terminus of the Aß peptide, despite being unstructured in themature Aß fibril, nonetheless affects Aß induced neurodegeneration in vivo. In order to understand the contribution of the N terminusof Aß to its aggregation behaviour, we have investigated anumber of rationally designed N-terminal mutants in vitro. We find that single amino acid mutations in this region affect significantlythe kinetics of Aß aggregation in vitro as measured by arange of spectroscopic techniques. Furthermore, we observe striking differences in the morphology of the aggregated speciesformed by these different Aß mutants when imaged with TEM or AFM and also in the ß-sheet content of their mature fibrils. Interestingly, mutants with an increased net charge or lower hydrophobicity tend to show slower aggregation kinetics, and to form more ordered aggregates whereas mutations that reduce net charge or increase hydrophobicity favour faster aggregation kinetics and poorly structured aggregates. In addition, the exposed hydrophobicity of aggregates formed in the early stages of aggregation is correlated to their toxicity. These findings demonstrate not only that the N-terminus of the Aß peptide plays a crucial role in its aggregation and toxicity but also suggest that this region of Aß may modulate in vivo toxicity by altering the conformations of aggregates that it forms.
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| 13. |
- Brorsson, Ann-Christin, et al.
(författare)
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Intrinsic determinants of neurotoxic aggregate formation by the amyloid beta peptide
- 2010
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 98:8, s. 1677-84
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which proteins aggregate into distinct structures ranging from prefibrillar oligomers to amyloid fibrils is key to the pathogenesis of many age-related degenerative diseases. We describe here for the Alzheimer's disease-related amyloid beta peptide (Abeta) an investigation of the sequence-based determinants of the balance between the formation of prefibrillar aggregates and amyloid fibrils. We show that by introducing single-point mutations, it is possible to convert the normally harmless Abeta40 peptide into a pathogenic species by increasing its relative propensity to form prefibrillar but not fibrillar aggregates, and, conversely, to abolish the pathogenicity of the highly neurotoxic E22G Abeta42 peptide by reducing its relative propensity to form prefibrillar species rather than mature fibrillar ones. This observation can be rationalized by the demonstration that whereas regions of the sequence of high aggregation propensity dominate the overall tendency to aggregate, regions with low intrinsic aggregation propensities exert significant control over the balance of the prefibrillar and fibrillar species formed, and therefore play a major role in determining the neurotoxicity of the Abeta peptide.
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| 14. |
- Conroy-Beam, Daniel, et al.
(författare)
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Assortative mating and the evolution of desirability covariation
- 2019
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Ingår i: Evolution and human behavior. - : Elsevier. - 1090-5138 .- 1879-0607. ; 40:5, s. 479-491
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Tidskriftsartikel (refereegranskat)abstract
- Mate choice lies dose to differential reproduction, the engine of evolution. Patterns of mate choice consequently have power to direct the course of evolution. Here we provide evidence suggesting one pattern of human mate choice-the tendency for mates to be similar in overall desirability-caused the evolution of a structure of correlations that we call the d factor. We use agent-based models to demonstrate that assortative mating causes the evolution of a positive manifold of desirability, d, such that an individual who is desirable as a mate along any one dimension tends to be desirable across all other dimensions. Further, we use a large cross-cultural sample with n = 14,478 from 45 countries around the world to show that this d-factor emerges in human samples, is a cross-cultural universal, and is patterned in a way consistent with an evolutionary history of assortative mating. Our results suggest that assortative mating can explain the evolution of a broad structure of human trait covariation.
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| 15. |
- Conroy-Beam, Daniel, et al.
(författare)
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Contrasting Computational Models of Mate Preference Integration Across 45 Countries
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Humans express a wide array of ideal mate preferences. Around the world, people desire romantic partners who are intelligent, healthy, kind, physically attractive, wealthy, and more. In order for these ideal preferences to guide the choice of actual romantic partners, human mating psychology must possess a means to integrate information across these many preference dimensions into summaries of the overall mate value of their potential mates. Here we explore the computational design of this mate preference integration process using a large sample of n = 14,487 people from 45 countries around the world. We combine this large cross-cultural sample with agent-based models to compare eight hypothesized models of human mating markets. Across cultures, people higher in mate value appear to experience greater power of choice on the mating market in that they set higher ideal standards, better fulfill their preferences in choice, and pair with higher mate value partners. Furthermore, we find that this cross-culturally universal pattern of mate choice is most consistent with a Euclidean model of mate preference integration.
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| 16. |
- Demmelmaier, Ingrid, 1960-, et al.
(författare)
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Does exercise intensity matter for fatigue during (neo-)adjuvant cancer treatment? The Phys-Can randomized clinical trial
- 2021
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 31:5, s. 1144-1159
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Tidskriftsartikel (refereegranskat)abstract
- Exercise during cancer treatment improves cancer-related fatigue (CRF), but the importance of exercise intensity for CRF is unclear. We compared the effects of high- vs low-to-moderate-intensity exercise with or without additional behavior change support (BCS) on CRF in patients undergoing (neo-)adjuvant cancer treatment. This was a multicenter, 2x2 factorial design randomized controlled trial (Clinical Trials NCT02473003) in Sweden. Participants recently diagnosed with breast (n = 457), prostate (n = 97) or colorectal (n = 23) cancer undergoing (neo-)adjuvant treatment were randomized to high intensity (n = 144), low-to-moderate intensity (n = 144), high intensity with BCS (n = 144) or low-to-moderate intensity with BCS (n = 145). The 6-month exercise intervention included supervised resistance training and home-based endurance training. CRF was assessed by Multidimensional Fatigue Inventory (MFI, five subscales score range 4-20), and Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F, score range 0-52). Multiple linear regression for main factorial effects was performed according to intention-to-treat, with post-intervention CRF as primary endpoint. Overall, 577 participants (mean age 58.7 years) were randomized. Participants randomized to high- vs low-to-moderate-intensity exercise had lower physical fatigue (MFI Physical Fatigue subscale; mean difference −1.05 [95% CI: −1.85, −0.25]), but the difference was not clinically important (ie <2). We found no differences in other CRF dimensions and no effect of additional BCS. There were few minor adverse events. For CRF, patients undergoing (neo-)adjuvant treatment for breast, prostate or colorectal cancer can safely exercise at high- or low-to-moderate intensity, according to their own preferences. Additional BCS does not provide extra benefit for CRF in supervised, well-controlled exercise interventions.
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| 17. |
- Denger, Christian, et al.
(författare)
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A Snapshot of the State of Practice in Software Development for Medical Devices
- 2007
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Ingår i: First International Symposium on Empirical Software Engineering and Measurement, 2007. ESEM 2007. - 1938-6451. - 9780769528861 ; , s. 485-487
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Konferensbidrag (refereegranskat)abstract
- The medical device industry is a constantly growing domain which makes use of more and more software products. Given the importance to this industry of dependable software components, rigorous software engineering techniques would seem to have an important role to play. However, in a recent survey of the industry we found a lower than expected rate of adoption of certain sound software engineering practices. To ensure and improve the quality of developed software products, whether they are stand-alone applications or embedded in complex systems, both the medical device industry as well as software engineers have to take action. Our survey is a first step in this direction and may help in identifying appropriate programs and future research topics.
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| 18. |
- Dore, Riccardo, et al.
(författare)
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Resistance to thyroid hormone induced tachycardia in RTHα syndrome
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in thyroid hormone receptor α1 (TRα1) cause Resistance to Thyroid Hormone α (RTHα), a disorder characterized by hypothyroidism in TRα1-expressing tissues including the heart. Surprisingly, we report that treatment of RTHα patients with thyroxine to overcome tissue hormone resistance does not elevate their heart rate. Cardiac telemetry in male, TRα1 mutant, mice indicates that such persistent bradycardia is caused by an intrinsic cardiac defect and not due to altered autonomic control. Transcriptomic analyses show preserved, thyroid hormone (T3)-dependent upregulation of pacemaker channels (Hcn2, Hcn4), but irreversibly reduced expression of several ion channel genes controlling heart rate. Exposure of TRα1 mutant male mice to higher maternal T3 concentrations in utero, restores altered expression and DNA methylation of ion channels, including Ryr2. Our findings indicate that target genes other than Hcn2 and Hcn4 mediate T3-induced tachycardia and suggest that treatment of RTHα patients with thyroxine in high dosage without concomitant tachycardia, is possible.
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| 19. |
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| 20. |
- Karlsson, L., et al.
(författare)
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The meaning of caring touch for healthcare professionals in an intensive care unit : A qualitative interview study
- 2022
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Ingår i: Intensive & Critical Care Nursing. - : Elsevier. - 0964-3397 .- 1532-4036. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- Background: The way health care professionals touch patients and relatives in the intensive care unit plays a significant role. A negative feeling can be caused by being touched in the wrong way, this is why a holistic approach with respect for the patient is important for the ability to make the patient and their relatives feel secure, avoiding unnecessary suffering.Aim: The aim of the study was to describe the meaning of caring touch that is given in the ICU from the health care professionals perspective.Method: Qualitative interview study with health care professionals in the intensive care unit, analysed using inductive content analysis, resulting in two themes and four main categories.Findings: Two themes emerged: Imperative touch and emotional touch and four main categories: touch as a natural tool, create a prerequisite for touch, empathetic touch and conversant touch.Conclusion: Caring touch can be used as a natural tool in the daily work in order to bring comfort and calm to the patient in the intensive care unit.
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| 21. |
- Kulakova, Alina, et al.
(författare)
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Chemometrics in Protein Formulation : Stability Governed by Repulsion and Protein Unfolding
- 2023
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Ingår i: Molecular Pharmaceutics. - 1543-8384. ; 20:6, s. 2951-2965
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic proteins can be challenging to develop due to their complexity and the requirement of an acceptable formulation to ensure patient safety and efficacy. To date, there is no universal formulation development strategy that can identify optimal formulation conditions for all types of proteins in a fast and reliable manner. In this work, high-throughput characterization, employing a toolbox of five techniques, was performed on 14 structurally different proteins formulated in 6 different buffer conditions and in the presence of 4 different excipients. Multivariate data analysis and chemometrics were used to analyze the data in an unbiased way. First, observed changes in stability were primarily determined by the individual protein. Second, pH and ionic strength are the two most important factors determining the physical stability of proteins, where there exists a significant statistical interaction between protein and pH/ionic strength. Additionally, we developed prediction methods by partial least-squares regression. Colloidal stability indicators are important for prediction of real-time stability, while conformational stability indicators are important for prediction of stability under accelerated stress conditions at 40 °C. In order to predict real-time storage stability, protein-protein repulsion and the initial monomer fraction are the most important properties to monitor.
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| 22. |
- Laine, Romain F., et al.
(författare)
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NanoJ : a high-performance open-source super-resolution microscopy toolbox
- 2019
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Ingår i: Journal of Physics D. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 52:16
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Forskningsöversikt (refereegranskat)abstract
- Super-resolution microscopy (SRM) has become essential for the study of nanoscale biological processes. This type of imaging often requires the use of specialised image analysis tools to process a large volume of recorded data and extract quantitative information. In recent years, our team has built an open-source image analysis framework for SRM designed to combine high performance and ease of use. We named it NanoJ-a reference to the popular ImageJ software it was developed for. In this paper, we highlight the current capabilities of NanoJ for several essential processing steps: spatio-temporal alignment of raw data (NanoJ-Core), super-resolution image reconstruction (NanoJ-SRRF), image quality assessment (NanoJ-SQUIRREL), structural modelling (NanoJ-VirusMapper) and control of the sample environment (NanoJ-Fluidics). We expect to expand NanoJ in the future through the development of new tools designed to improve quantitative data analysis and measure the reliability of fluorescent microscopy studies.
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| 23. |
- Larsson, L-G, et al.
(författare)
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Symptoms related to snoring and sleep apnoea in subjects with chronic bronchitis : report from the Obstructive Lung Disease in Northern Sweden study
- 1997
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Ingår i: Respiratory Medicine. - 0954-6111 .- 1532-3064. ; 91:1, s. 5-12
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Tidskriftsartikel (refereegranskat)abstract
- To assess the relationship between chronic bronchitis and obstructive sleep apnoea, a postal survey was performed. A postal questionnaire was sent to 523 subjects identified as having chronic bronchitis or long-standing cough and sputum production in the Obstructive Lung Disease in Northern Sweden Study I (OLIN I). In 1986-88, all 6610 adults born in 1919-20, 1934-35 and 1949-50 living in representative areas in Northern Sweden were screened for airway diseases according to different methods. A random sample of healthy adults identified in the screening were chosen as references (n = 625). Subjects were asked about a variety of airway symptoms, smoking habits and symptoms related to obstructive sleep apnoea syndrome (OSAS). In the bronchitic group, 20% did not report bronchitic symptoms in the present study, and 26% of the formerly healthy reference group reported at least one bronchitic symptom in the present study. Snoring, apnoea and liability to 'nod off' during activity were much more common in the bronchitic group in both men and women, and most common in men, as expected. Snoring was reported by 29% of the men in the bronchitic group and by 14% in the reference group. In women, the corresponding figures were 14 and 8%, respectively, and for apnoea, the figures were 25 vs. 11% in men and 6 vs. 4% in women. The prevalence of OSAS symptoms was similar in subjects with attacks of breathlessness, long-standing cough, sputum production and recurrent wheezing. Bronchitic symptoms may influence quality of sleep and contribute to daytime tiredness, but this does not fully explain the high prevalence of snoring and apnoea reported by subjects in this cohort. This study indicates a positive correlation between chronic bronchitis and OSAS, but sleep studies are required to confirm this
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| 24. |
- Lindskog, Stefan, et al.
(författare)
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Phenotypic expression of a family with multiple endocrine neoplasia type 2A due to a RET mutation at codon 618
- 2004
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 91:6, s. 713-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple endocrine neoplasia type 2A (MEN2A) is caused by missense mutations in the RET proto-oncogene on chromosome 10. This paper reports the phenotypic expression of a family with MEN2A, in which serine substitutes for cysteine at codon 618 in exon 10 of the RET gene. It was first claimed that medullary thyroid cancer (MTC) with this rare mutation led to mild disease; this has recently been updated to intermediate-high risk, based on stratified genetic information. METHODS: The family was mapped over six generations. In 1971 family members were invited to join a screening programme. Genetic testing was started in 1994. RESULTS: Twenty-two individuals with MTC were identified, 16 by the screening programme. One screened patient had a phaeochromocytoma and four had hyperparathyroidism. At surgery for MTC 12 patients had local tumour metastases and two young patients also had liver metastases. No screened patient died from MTC during a mean observation time of 19 years. Six other family members were diagnosed with MTC by signs and symptoms, five of whom died from MTC. CONCLUSION: Because of the great interindividual differences in tumour aggressiveness within the family it is impossible to predict whether an individual gene carrier will have an aggressive MTC or not. This unpredictability is an additional argument, besides those obtained in stratified genetic studies, for operating on gene carriers at young age.
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| 25. |
- Lundström, Jan O., et al.
(författare)
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Transstadial Transmission of Francisella tularensis holarctica in Mosquitoes, Sweden
- 2011
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 17:5, s. 794-799
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Tidskriftsartikel (refereegranskat)abstract
- In Sweden, human cases of tularemia caused by Francisella tularensis holarctica are assumed to be transmitted by mosquitoes, but how mosquito vectors acquire and transmit the bacterium is not clear. To determine how transmission of this bacterium occurs, mosquito larvae were collected in an area where tularemia is endemic, brought to the laboratory, and reared to adults in their original pond water. Screening of adult mosquitoes by real-time PCR demonstrated F tularensis IpnA sequences in 14 of the 48 mosquito pools tested; IpnA sequences were demonstrated in 6 of 9 identified mosquito species. Further analysis confirmed the presence of F tularensis holarctica-specific 30-bp deletion region sequences (FtM19inDel) in water from breeding containers and in 3 mosquito species (Aedes sticticus, Ae. vexans, and Ae. punctor) known to take blood from humans. Our results suggest that the mosquitoes that transmit F tularensis holarctica during tularemia outbreaks acquire the bacterium already as larvae.
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