| 1. |
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| 2. |
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| 3. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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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. |
- Kirsebom, O. S., et al.
(författare)
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Discovery of an Exceptionally Strong β -Decay Transition of F 20 and Implications for the Fate of Intermediate-Mass Stars
- 2019
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Ingår i: Physical Review Letters. - 0031-9007. ; 123:26
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Tidskriftsartikel (refereegranskat)abstract
- A significant fraction of stars between 7 and 11 solar masses are thought to become supernovae, but the explosion mechanism is unclear. The answer depends critically on the rate of electron capture on Ne20 in the degenerate oxygen-neon stellar core. However, because of the unknown strength of the transition between the ground states of Ne20 and F20, it has not previously been possible to fully constrain the rate. By measuring the transition, we establish that its strength is exceptionally large and that it enhances the capture rate by several orders of magnitude. This has a decisive impact on the evolution of the core, increasing the likelihood that the star is (partially) disrupted by a thermonuclear explosion rather than collapsing to form a neutron star. Importantly, our measurement resolves the last remaining nuclear physics uncertainty in the final evolution of degenerate oxygen-neon stellar cores, allowing future studies to address the critical role of convection, which at present is poorly understood
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| 6. |
- Claassen, Yvette H. M., et al.
(författare)
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Treatment and survival of rectal cancer patients over the age of 80 years : a EURECCA international comparison
- 2018
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 119:4, s. 517-522
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+.METHODS: Patients of >= 80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients.RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO.CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.
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| 7. |
- Lagrange, A. -M., et al.
(författare)
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Post-conjunction detection of beta Pictoris b with VLT/SPHERE
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 621
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Tidskriftsartikel (refereegranskat)abstract
- Context. With an orbital distance comparable to that of Saturn in the solar system, beta Pictoris b is the closest (semi-major axis similar or equal to 9 au) exoplanet that has been imaged to orbit a star. Thus it offers unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to beta Pictoris have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet's orbital parameters.Aims. We aimed at further constraining beta Pictoris b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit.Methods. We used SPHERE at the VLT to precisely monitor the orbital motion of beta beta Pictoris b since first light of the instrument in 2014.Results. We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6 au) and prevented further detection. We redetected beta Pictoris b on the northeast side of the disk at a separation of 139 mas and a PA of 30 degrees in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of a = 9.0 +/- 0.5 au (1 sigma), it definitely excludes previously reported possible long orbital periods, and excludes beta Pictoris b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.
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| 8. |
- Moschner, K., et al.
(författare)
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Relativistic Coulomb excitation of 88Kr
- 2016
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Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 94:5
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the systematics of mixed-symmetry states in N=52 isotones, a relativistic Coulomb excitation experiment was performed during the PreSPEC campaign at the GSI Helmholtzzentrum für Schwerionenforschung to determine E2 transition strengths to 2+ states of the radioactive nucleus 88Kr. Absolute transition rates could be measured towards the first and third 2+ states. For the latter a mixed-symmetry character is suggested on the basis of the indication for a strong M1 transition to the fully symmetric 2+1 state, extending the knowledge of the N=52 isotones below Z=40. A comparison with the proton-neutron interacting boson model and shell-model predictions is made and supports the assignment.
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| 9. |
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| 10. |
- van der Valk, Ralf J P, et al.
(författare)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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| 11. |
- Delerue, N., et al.
(författare)
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A Massive Open Online Course on Particle Accelerators
- 2018. - 9
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1067
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Konferensbidrag (refereegranskat)abstract
- The TIARA (Test Infrastructure and Accelerator Research Area) project funded by the European Union 7th framework programme made a survey of provision of education and training in accelerator science in Europe. This survey highlighted the need for more training opportunities targeting undergraduate-level students. This need is now being addressed by the European Union H2020 project ARIES (Accelerator Research and Innovation for European Science and Society) via the preparation of a Massive Open Online Course (MOOC) on particle accelerator science and engineering. We present here the current status of this project, the main elements of the syllabus, how it will be delivered, and the schedule for providing the course.
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| 12. |
- Felix, Janine F, et al.
(författare)
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Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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| 15. |
- Møller, M. H., et al.
(författare)
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Scandinavian SSAI clinical practice guideline on choice of inotropic agent for patients with acute circulatory failure
- 2018
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Ingår i: Acta Anaesthesiologica Scandinavica. - Hoboken : John Wiley & Sons. - 0001-5172 .- 1399-6576. ; 62:4, s. 420-450
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Adult critically ill patients often suffer from acute circulatory failure and those with low cardiac output may be treated with inotropic agents. The aim of this Scandinavian Society of Anaesthesiology and Intensive Care Medicine guideline was to present patient-important treatment recommendations on this topic.METHODS: This guideline was developed according to GRADE. We assessed the following subpopulations of patients with shock: (1) shock in general, (2) septic shock, (3) cardiogenic shock, (4) hypovolemic shock, (5) shock after cardiac surgery, and (6) other types of shock, including vasodilatory shock. We assessed patient-important outcome measures, including mortality and serious adverse reactions.RESULTS: For all patients, we suggest against the routine use of any inotropic agent, including dobutamine, as compared to placebo/no treatment (very low quality of evidence). For patients with shock in general, and in those with septic and other types of shock, we suggest using dobutamine rather than levosimendan or epinephrine (very low quality of evidence). For patients with cardiogenic shock and in those with shock after cardiac surgery, we suggest using dobutamine rather than milrinone (very low quality of evidence). For the other clinical questions, we refrained from giving any recommendations or suggestions.CONCLUSIONS: We suggest against the routine use of any inotropic agent in adult patients with shock. If used, we suggest using dobutamine rather than other inotropic agents for the majority of patients, however, the quality of evidence was very low, implying high uncertainty on the balance between the benefits and harms of inotropic agents.
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| 16. |
- Anderson, J. P., et al.
(författare)
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A nearby super-luminous supernova with a long pre-maximum plateau and strong C (II) features
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
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Tidskriftsartikel (refereegranskat)abstract
- Context. Super-luminous supernovae (SLSNe) are rare events defined as being significantly more luminous than normal terminal stellar explosions. The source of the additional power needed to achieve such luminosities is still unclear. Discoveries in the local Universe (i.e. z < 0.1) are scarce, but afford dense multi-wavelength observations. Additional low-redshift objects are therefore extremely valuable.Aims. We present early-time observations of the type I SLSN ASASSN-18km/SN 2018bsz. These data are used to characterise the event and compare to literature SLSNe and spectral models. Host galaxy properties are also analysed.Methods. Optical and near-IR photometry and spectroscopy were analysed. Early-time ATLAS photometry was used to constrain the rising light curve. We identified a number of spectral features in optical-wavelength spectra and track their time evolution. Finally, we used archival host galaxy photometry together with H( II )region spectra to constrain the host environment.Results. ASASSN-18km/SN 2018bsz is found to be a type I SLSN in a galaxy at a redshift of 0.0267 (111 Mpc), making it the lowest-redshift event discovered to date. Strong C- II lines are identified in the spectra. Spectral models produced by exploding a Wolf-Rayet progenitor and injecting a magnetar power source are shown to be qualitatively similar to ASASSN-18km/SN 2018bsz, contrary to most SLSNe-I that display weak or non-existent C (II) lines. ASASSN-18km/SN 2018bsz displays along, slowly rising, red plateau of >26 days, before a steeper, faster rise to maximum. The host has an absolute magnitude of -19.8 mag (r), a mass of M-* = 1.5(-0.33)(+0.08) x 10(9) M-circle dot, and a star formation rate of =0.50(-0.19)(+2.22) M-circle dot yr(-1). A nearby H (II) region has an oxygen abundance (O3N2) of 8.31 +/- 0.01 dex.
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| 17. |
- Bexelius, T., et al.
(författare)
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Stress among medical students during clinical courses : a longitudinal study using contextual activity sampling system
- 2019
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Ingår i: International Journal of Medical Education. - : IJME. - 2042-6372. ; 10, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate medical students’ experiences of stress and other emotions related to their professional roles, as defined by the CanMEDS framework, by using the Contextual Activity Sampling System (CASS).Methods: Ninety-eight medical students agreed to participate of whom 74 completed this longitudinal cohort study. Data was collected between 6th and 8th term via CASS methodology: A questionnaire was e-mailed to the participants every 3rd week (21questionnaires/measurements) during clinical rotations and scientific project work term. Emotions were measured by a 7-point Likert scale (e.g., maximum stress = 7). Answers were registered through mobile technology. We used a linear mixed-model regression approach to study the association between stress over time in relation to socio-demographic and learning activities related to CanMEDS roles.Results: Participants completed 1390 questionnaires. Mean stress level over all time points was 3.6. Stress was reported as highest during the scientific project term. Learning activities related to ‘Communicator,’ ‘Collaborator,’ ‘Scholar,’ ‘Manager’ and ‘Professional’ were associated with increased stress, e.g. ’Scholar’ increased stress with 0.5 points (t=3.91, p<0.001). A reduced level of stress was associated with ’Health Advocate’ of 0.39 points (t=-2.15, p=0.03). No association between perceived stress and demographic factors, such as gender or age was found.Conclusions: An association between different learning activities related to CanMEDS Roles and feelings of stress were noted. The CASS methodology was found to be useful when observing learning experiences and might support educational development by identifying course activities linked to stress.
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| 18. |
- Broesby-Olsen, Sigurd, et al.
(författare)
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Multidisciplinary Management of Mastocytosis : Nordic Expert Group Consensus
- 2016
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 96:5
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Tidskriftsartikel (refereegranskat)abstract
- Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.
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| 19. |
- Calissendorff, Jan, et al.
(författare)
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A Prospective Investigation of Graves' Disease and Selenium : Thyroid Hormones, Auto-Antibodies and Self-Rated Symptoms.
- 2015
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Ingår i: European thyroid journal. - : Bioscientifica. - 2235-0640 .- 2235-0802. ; 4:2, s. 93-98
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Graves' thyrotoxicosis tachycardia, weight loss and mental symptoms are common. Recovery takes time and varies between patients. Treatment with methimazole reduces thyroid hormone levels. According to previous research, this reduction has been faster if selenium (Se) is added.OBJECTIVE: The objective was to investigate whether supplementing the pharmacologic treatment with Se could change the immune mechanisms, hormone levels and/or depression and anxiety.METHODS: We prospectively investigated 38 patients with initially untreated thyrotoxicosis by measuring the thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid receptor antibodies and thyroid peroxidase auto-antibodies before medication and at 6, 18 and 36 weeks after commencing treatment with methimazole and levo-thyroxine, with a randomized blinded oral administration of 200 µg Se/day or placebo. The selenoprotein P concentration was determined in plasma at inclusion and after 36 weeks. The patients were also assessed with questionnaires about depression, anxiety and self-rated symptoms before medication was started and after 36 weeks.RESULTS: FT4 decreased more in the Se group at 18 weeks (14 vs. 17 pmol/l compared to the placebo group, p = 0.01) and also at 36 weeks (15 vs. 18 pmol/l, p = 0.01). The TSH increased more in the Se group at 18 weeks (0.05 vs. 0.02 mIU/l, p = 0.04). The depression and anxiety scores were similar in both groups. In the Se group, the depression rates correlated negatively with FT3 and positively with TSH. This was not seen in the placebo group.CONCLUSIONS: Se supplementation can enhance biochemical restoration of hyperthyroidism, but whether this could shorten clinical symptoms of thyrotoxicosis and reduce mental symptoms must be investigated further.
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| 20. |
- Claussen, Anetta, et al.
(författare)
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Impact of demographics and disease progression on the relationship between glucose and HbA1c
- 2017
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Ingår i: European Journal of Pharmaceutical Sciences. - : ELSEVIER SCIENCE BV. - 0928-0987 .- 1879-0720. ; 104, s. 417-423
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Tidskriftsartikel (refereegranskat)abstract
- Context: Several studies have shown that the relationship between mean plasma glucose (MPG) and glycated haemoglobin (HbA1c) may vary across populations. Especially race has previously been referred to shift the regression line that links MPG to HbA1c at steady-state (Herman & Cohen, 2012).Objective: To assess the influence of demographic and disease progression-related covariates on the intercept of the estimated linear MPG-HbA1c relationship in a longitudinal model.Data: Longitudinal patient-level data from 16 late-phase trials in type 2 diabetes with a total of 8927 subjects was used to study covariates for the relationship between MPG and HbA1c. The analysed covariates included age group, HMI, gender, race, diabetes duration, and pre-trial treatment. Differences between trials were taken into account by estimating a trial-to-trial variability component.Participants: Participants included 47% females and 20% above 65 years. 77% were Caucasian, 9% were Asian, 5% were Black and the remaining 9% were analysed together as other races.Analysis: Estimates of the change in the intercept of the MPG-HbA1c relationship due to the mentioned covariates were determined using a longitudinal model.Results: The analysis showed that pre-trial treatment with insulin had the most pronounced impact associated with a 0.34% higher HbA1c at a given MPG. However, race, diabetes duration and age group also had an impact on the MPG-HbA1c relationship.Conclusion: Our analysis shows that the relationship between MPG and HbA1c is relatively insensitive to covariates, but shows small variations across populations, which may be relevant to take into account when predicting HbA1c response based on MPG measurements in clinical trials.
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| 21. |
- Clayton, Aled, et al.
(författare)
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Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017
- 2018
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Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.
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| 22. |
- Gorkhover, Tais, et al.
(författare)
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Femtosecond X-ray Fourier holography imaging of free-flying nanoparticles
- 2018
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Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 12:3, s. 150-153
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Tidskriftsartikel (refereegranskat)abstract
- Ultrafast X-ray imaging on individual fragile specimens such as aerosols 1 , metastable particles 2 , superfluid quantum systems 3 and live biospecimens 4 provides high-resolution information that is inaccessible with conventional imaging techniques. Coherent X-ray diffractive imaging, however, suffers from intrinsic loss of phase, and therefore structure recovery is often complicated and not always uniquely defined 4,5 . Here, we introduce the method of in-flight holography, where we use nanoclusters as reference X-ray scatterers to encode relative phase information into diffraction patterns of a virus. The resulting hologram contains an unambiguous three-dimensional map of a virus and two nanoclusters with the highest lateral resolution so far achieved via single shot X-ray holography. Our approach unlocks the benefits of holography for ultrafast X-ray imaging of nanoscale, non-periodic systems and paves the way to direct observation of complex electron dynamics down to the attosecond timescale.
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| 23. |
- Hartoog, O. E., et al.
(författare)
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VLT/X-Shooter spectroscopy of the afterglow of the Swift GRB 130606A Chemical abundances and reionisation at z similar to 6
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
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Tidskriftsartikel (refereegranskat)abstract
- Context: The reionisation of the Universe is a process that is thought to have ended around z similar to 6, as inferred from spectroscopy of distant bright background sources, such as quasars (QSO) and gamma-ray burst (GRB) afterglows. Furthermore, spectroscopy of a GRB afterglow provides insight in its host galaxy, which is often too dim and distant to study otherwise.Aims: For the Swift GRB 130606A at z = 5.913 we have obtained a high S/N spectrum covering the full optical and near-IR wavelength region at intermediate spectral resolution with VLT/X-Shooter. We aim to measure the degree of ionisation of the intergalactic medium (IGM) between z = 5.02-5.84 and to study the chemical abundance pattern and dust content of its host galaxy.Methods: We estimated the UV continuum of the GRB afterglow using a power-law extrapolation, then measured the flux decrement due to absorption at Ly alpha,beta, and gamma wavelength regions. Furthermore, we fitted the shape of the red damping wing of Lya. The hydrogen and metal absorption lines formed in the host galaxy were fitted with Voigt profiles to obtain column densities. We investigated whether ionisation corrections needed to be applied.Results: Our measurements of the Ly alpha-forest optical depth are consistent with previous measurements of QSOs, but have a much smaller uncertainty. The analysis of the red damping wing yields a neutral fraction x(HI) < 0.05 (3 sigma). We obtain column density measurements of H, Al, Si, and Fe; for C, O, S and Ni we obtain limits. The ionisation due to the GRB is estimated to be negligible (corrections < 0.03 dex), but larger corrections may apply due to the pre-existing radiation field (up to 0.4 dex based on sub-DLA studies). Assuming that [Si/Fe] = +0.79 +/- 0.13 is due to dust depletion, the dust-to-metal ratio is similar to the Galactic value.Conclusions: Our measurements confirm that the Universe is already predominantly ionised over the redshift range probed in this work, but was slightly more neutral at z > 5.6. GRBs are useful probes of the ionisation state of the IGM in the early Universe, but because of internal scatter we need a larger statistical sample to draw robust conclusions. The high [Si/Fe] in the host can be due to dust depletion, a-element enhancement, or a combination of both. The very high value of [Al/Fe] = 2.40 +/- 0.78 might be due to a proton capture process and is probably connected to the stellar population history. We estimate the host metallicity to be -1.7 < [M/H] < -0.9 (2%-13% of solar).
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| 24. |
- Iablonskyi, D., et al.
(författare)
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Slow Interatomic Coulombic Decay of Multiply Excited Neon Clusters
- 2016
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Ingår i: Physical Review Letters. - 0031-9007. ; 117:27
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Tidskriftsartikel (refereegranskat)abstract
- Ne clusters (∼5000 atoms) were resonantly excited (2p→3s) by intense free electron laser (FEL) radiation at FERMI. Such multiply excited clusters can decay nonradiatively via energy exchange between at least two neighboring excited atoms. Benefiting from the precise tunability and narrow bandwidth of seeded FEL radiation, specific sites of the Ne clusters were probed. We found that the relaxation of cluster surface atoms proceeds via a sequence of interatomic or intermolecular Coulombic decay (ICD) processes while ICD of bulk atoms is additionally affected by the surrounding excited medium via inelastic electron scattering. For both cases, cluster excitations relax to atomic states prior to ICD, showing that this kind of ICD is rather slow (picosecond range). Controlling the average number of excitations per cluster via the FEL intensity allows a coarse tuning of the ICD rate.
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| 25. |
- Latvala, Siiri, et al.
(författare)
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Optimization of an air-liquid interface exposure system for assessing toxicity of airborne nanoparticles
- 2016
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Ingår i: Journal of Applied Toxicology. - : Wiley. - 0260-437X .- 1099-1263.
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Tidskriftsartikel (refereegranskat)abstract
- The use of refined toxicological methods is currently needed for characterizing the risks of airborne nanoparticles (NPs) to human health. To mimic pulmonary exposure, we have developed an air-liquid interface (ALI) exposure system for direct deposition of airborne NPs on to lung cell cultures. Compared to traditional submerged systems, this allows more realistic exposure conditions for characterizing toxicological effects induced by airborne NPs. The purpose of this study was to investigate how the deposition of silver NPs (AgNPs) is affected by different conditions of the ALI system. Additionally, the viability and metabolic activity of A549 cells was studied following AgNP exposure. Particle deposition increased markedly with increasing aerosol flow rate and electrostatic field strength. The highest amount of deposited particles (2.2 μg cm-2) at cell-free conditions following 2 h exposure was observed for the highest flow rate (390 ml min-1) and the strongest electrostatic field (±2 kV). This was estimated corresponding to deposition efficiency of 94%. Cell viability was not affected after 2 h exposure to clean air in the ALI system. Cells exposed to AgNPs (0.45 and 0.74 μg cm-2) showed significantly (P < 0.05) reduced metabolic activities (64 and 46%, respectively). Our study shows that the ALI exposure system can be used for generating conditions that were more realistic for in vitro exposures, which enables improved mechanistic and toxicological studies of NPs in contact with human lung cells.
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| 26. |
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| 27. |
- Marcus, Monica M, et al.
(författare)
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Alpha7 nicotinic acetylcholine receptor agonists and PAMs as adjunctive treatment in schizophrenia. An experimental study.
- 2016
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 26:9, s. 1401-11
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Tidskriftsartikel (refereegranskat)abstract
- Nicotine has been found to improve cognition and reduce negative symptoms in schizophrenia and a genetic and pathophysiological link between the α7 nicotinic acetylcholine receptors (nAChRs) and schizophrenia has been demonstrated. Therefore, there has been a large interest in developing drugs affecting the α7 nAChRs for schizophrenia. In the present study we investigated, in rats, the effects of a selective α7 agonist (PNU282987) and a α7 positive allosteric modulator (PAM; NS1738) alone and in combination with the atypical antipsychotic drug risperidone for their utility as adjunct treatment in schizophrenia. Moreover we also investigated their utility as adjunct treatment in depression in combination with the SSRI citalopram. We found that NS1738 and to some extent also PNU282987, potentiated a subeffective dose of risperidone in the conditioned avoidance response test. Both drugs also potentiated the effect of a sub-effective concentration of risperidone on NMDA-induced currents in pyramidal cells of the medial prefrontal cortex. Moreover, NS1738 and PNU282987 enhanced recognition memory in the novel object recognition test, when given separately. Both drugs also potentiated accumbal but not prefrontal risperidone-induced dopamine release. Finally, PNU282987 reduced immobility in the forced swim test, indicating an antidepressant-like effect. Taken together, our data support the utility of drugs targeting the α7 nAChRs, perhaps especially α7 PAMs, to potentiate the effect of atypical antipsychotic drugs. Moreover, our data suggest that α7 agonists and PAMs can be used to ameliorate cognitive symptoms in schizophrenia and depression.
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| 28. |
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| 29. |
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| 30. |
- Nieminen, Markku S, et al.
(författare)
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The role of levosimendan in acute heart failure complicating acute coronary syndrome: A review and expert consensus opinion.
- 2016
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 218, s. 150-157
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Tidskriftsartikel (refereegranskat)abstract
- Acute heart failure and/or cardiogenic shock are frequently triggered by ischemic coronary events. Yet, there is a paucity of randomized data on the management of patients with heart failure complicating acute coronary syndrome, as acute coronary syndrome and cardiogenic shock have frequently been defined as exclusion criteria in trials and registries. As a consequence, guideline recommendations are mostly driven by observational studies, even though these patients have a particularly poor prognosis compared to heart failure patients without signs of coronary artery disease. In acute heart failure, and especially in cardiogenic shock related to ischemic conditions, vasopressors and inotropes are used. However, both pathophysiological considerations and available clinical data suggest that these treatments may have disadvantageous effects. The inodilator levosimendan offers potential benefits due to a range of distinct effects including positive inotropy, restoration of ventriculo-arterial coupling, increases in tissue perfusion, and anti-stunning and anti-inflammatory effects. In clinical trials levosimendan improves symptoms, cardiac function, hemodynamics, and end-organ function. Adverse effects are generally less common than with other inotropic and vasoactive therapies, with the notable exception of hypotension. The decision to use levosimendan, in terms of timing and dosing, is influenced by the presence of pulmonary congestion, and blood pressure measurements. Levosimendan should be preferred over adrenergic inotropes as a first line therapy for all ACS-AHF patients who are under beta-blockade and/or when urinary output is insufficient after diuretics. Levosimendan can be used alone or in combination with other inotropic or vasopressor agents, but requires monitoring due to the risk of hypotension.
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| 31. |
- Olsson Möller, U, et al.
(författare)
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Bridging gaps in everyday life : a free-listing approach to explore the variety of activities performed by physiotherapists in specialized palliative care
- 2018
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Ingår i: BMC Palliative Care. - 1472-684X .- 1472-684X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A growing body of studies indicate benefits of physiotherapy for patients in palliative care, for symptom relief and wellbeing. Though physiotherapists are increasingly acknowledged as important members of palliative care teams, they are still an underutilized source and not fully recognized. The aim of this study was to explore the variety of activities described by physiotherapists in addressing the needs and problems of patients and their families in specialized palliative care settings.METHODS: Using a free-listing approach, ten physiotherapists working in eight specialized palliative care settings in Sweden described as precisely and in as much detail as possible different activities in which patients and their families were included (directly or indirectly) during 10 days. The statements were entered into NVivo and analysed using qualitative content analysis. Statements containing more than one activity were categorized per activity.RESULTS: In total, 264 statements, containing 504 varied activities, were coded into seven categories: Counteracting a declining physical function; Informing, guiding and educating; Observing, assessing and evaluating; Attending to signs and symptoms; Listening, talking with and understanding; Caring for basic needs; and Organizing, planning and coordinating. In practice, however, the activities were intrinsically interwoven. The activities showed how physiotherapists aimed, through care for the body, to address patients' physical, psychological, social and existential needs, counteracting the decline in a patient's physical function and wellbeing. The activities also revealed a great variation, in relation not only to what they did, but also to their holistic and inseparable nature with regard to why, how, when, where, with whom and for whom the activities were carried out, which points towards a well-adopted person-centred palliative care approach.CONCLUSIONS: The study provides hands-on descriptions of how person-centred palliative care is integrated in physiotherapists' everyday activities. Physiotherapists in specialized palliative care help patients and families to bridge the gap between their real and ideal everyday life with the aim to maximize security, autonomy and wellbeing. The concrete examples included can be used in understanding the contribution of physiotherapists to the palliative care team and inform future research interventions and outcomes.
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| 32. |
- Olsson Möller, U, et al.
(författare)
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Bridging gaps in everyday life : a free-listing approach to explore the variety of activities performed by physiotherapists in specialized palliative care
- 2018
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Ingår i: BMC Palliative Care. - : BioMed Central Ltd.. - 1472-684X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A growing body of studies indicate benefits of physiotherapy for patients in palliative care, for symptom relief and wellbeing. Though physiotherapists are increasingly acknowledged as important members of palliative care teams, they are still an underutilized source and not fully recognized. The aim of this study was to explore the variety of activities described by physiotherapists in addressing the needs and problems of patients and their families in specialized palliative care settings. METHODS: Using a free-listing approach, ten physiotherapists working in eight specialized palliative care settings in Sweden described as precisely and in as much detail as possible different activities in which patients and their families were included (directly or indirectly) during 10 days. The statements were entered into NVivo and analysed using qualitative content analysis. Statements containing more than one activity were categorized per activity. RESULTS: In total, 264 statements, containing 504 varied activities, were coded into seven categories: Counteracting a declining physical function; Informing, guiding and educating; Observing, assessing and evaluating; Attending to signs and symptoms; Listening, talking with and understanding; Caring for basic needs; and Organizing, planning and coordinating. In practice, however, the activities were intrinsically interwoven. The activities showed how physiotherapists aimed, through care for the body, to address patients' physical, psychological, social and existential needs, counteracting the decline in a patient's physical function and wellbeing. The activities also revealed a great variation, in relation not only to what they did, but also to their holistic and inseparable nature with regard to why, how, when, where, with whom and for whom the activities were carried out, which points towards a well-adopted person-centred palliative care approach. CONCLUSIONS: The study provides hands-on descriptions of how person-centred palliative care is integrated in physiotherapists' everyday activities. Physiotherapists in specialized palliative care help patients and families to bridge the gap between their real and ideal everyday life with the aim to maximize security, autonomy and wellbeing. The concrete examples included can be used in understanding the contribution of physiotherapists to the palliative care team and inform future research interventions and outcomes.
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| 33. |
- Pareek, Manan, et al.
(författare)
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Single and multiple cardiovascular biomarkers in subjects without a previous cardiovascular event
- 2017
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; , s. 1648-1659
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Tidskriftsartikel (refereegranskat)abstract
- Aims To assess the incremental value of biomarkers, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), growth differentiation factor 15 (GDF-15), and procollagen type 1 N-terminal propeptide (P1NP), in predicting incident cardiovascular events and mortality among asymptomatic individuals from the general population, beyond traditional risk factors, including fasting glucose and renal function (cystatin C), medication use, and echocardiographic measures. Methods and results Prospective population-based cohort study of 1324 subjects without a previous cardiovascular event, who underwent baseline echocardiography and biomarker assessment between 2002 and 2006. The clinical endpoint was the composite of myocardial infarction, invasively treated stable/unstable ischemic heart disease, heart failure, stroke, or all-cause mortality. Predictive capabilities were evaluated using Cox proportional-hazards regression, Harrell's concordance index (C-index), and net reclassification improvement. Median age was 66 (interquartile range: 60-70) years, and 413 (31%) were female. During median 8.6 (interquartile range: 8.1-9.2) follow-up years, 368 (28%) composite events occurred. NT-proBNP, hs-TnT, GDF-15, and IL-6 were significantly associated with outcome, independently of traditional risk factors, medications, and echocardiography ( p < 0.05 for all). Separate addition of NT-proBNP and GDF-15 to traditional risk factors, medications, and echocardiographic measurements provided significant improvements in discriminative ability (NT-proBNP: C-index 0.714 vs. 0.703, p = 0.03; GDF-15: C-index 0.721 vs. 0.703, p = 0.02). Both biomarkers remained significant predictors of outcome upon inclusion in the same model ( p < 0.05 for both). Conclusions NT-proBNP and GDF-15 each enhance prognostication beyond traditional risk factors, glucose levels, renal function, and echocardiography in individuals without known cardiovascular disease.
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| 34. |
- Parodis, Ioannis, et al.
(författare)
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The impact of belimumab and rituximab on health-related quality of life in patients with systemic lupus erythematosus
- 2019
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Ingår i: Arthritis care & research. - : John Wiley & Sons. - 2151-464X .- 2151-4658. ; 71:6, s. 811-821
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Accumulating evidence supports an impaired health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). We investigated the effects of two biologic treatments on SLE patients' HRQoL.METHODS: SLE patients from the Karolinska University Hospital treated with belimumab (n=34) or rituximab (n=35) were included; Swedish population-based age- and sex-matched norms served as controls. Data were collected prospectively at treatment initiation and at months 3, 6, 12 and 24; these included the SF-36, FACIT-Fatigue, EQ-5D, and Stanford HAQ-DI.RESULTS: Substantial decrements from Swedish norms were observed across all SF-36 domains at baseline. Belimumab-treated patients reported gradual improvements in the SF-36 physical component summary (significant from month 12; P=0.023) and FACIT-Fatigue (significant by month 24; P=0.001), no changes in EQ-5D scores, and improvements in HAQ-DI by month 6 (P=0.014). Rituximab-treated patients showed rapid improvements in the SF-36 mental component summary and FACIT-Fatigue by month 3 (P=0.031 and P=0.007, respectively), as well as improvements in EQ-5D at month 6 (P=0.016) and HAQ-DI at month 3 (P=0.033). Based on baseline evaluations, patients receiving antimalarial agents (n=33) performed better in the SF-36 social functioning (P=0.022) and mental health (P=0.023) domains compared to patients who were not (n=36).CONCLUSION: Our findings corroborated considerable HRQoL impairments in SLE patients. Patients' perceptions of HRQoL showed discrepant patterns over time in the two treatment groups, and could provide additional information along with the clinical evaluation of biologic therapy in SLE. Survey on the effects of antimalarial agents on SLE patients' HRQoL in larger cohorts is merited.
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| 35. |
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| 36. |
- Pedersen, K. B., et al.
(författare)
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Fixation stability and implication for multifocal electroretinography in patients with neovascular age-related macular degeneration after anti-VEGF treatment
- 2016
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Ingår i: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 0721-832X .- 1435-702X. ; 254:10, s. 1897-1908
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To quantify fixation stability in patients with neovascular age-related macular degeneration (nAMD) at baseline, 3 and 6 months after anti-vascular endothelial growth factor (anti-VEGF) treatment and furthermore asses the implications of an unsteady fixation for multifocal electroretinography (mfERG) measurements. Methods: Fifty eyes of 50 nAMD patients receiving intravitreal anti-VEGF treatment with either bevacizumab or ranibizumab and eight eyes of eight control subjects were included. Fixation stability measurements were performed with the Eye-Link eyetracking system and the retinal area in degrees2 (deg2) containing the 68 % most frequently used fixation points (RAF68) was calculated. MfERG P1 amplitude and implicit time were analyzed in six concentric rings and as a summed response. Patients were examined at baseline, 3 and 6 months. Four different mfERG recordings were performed for the control subjects to mimic an involuntary unstable fixation: normal central fixation, 2.4°, 4.8°, and 7.1° fixation instability. Results: For control subjects, a fixation instability of 2.4° (corresponding to the central hexagon) did not reduce mfERG ring amplitudes significantly, whereas 4.8° and 7.1° fixation instability reduced the amplitudes significantly in rings 1 and 2 (p <0.001) as well as in the peripheral rings in the 7.1° instability condition (p <0.001). Fixation stability improved non-significantly for patients at 3 and 6 months. The size of the retinal area of fixation was at baseline, 3 and 6 months negatively correlated to visual acuity (VA) (rbaseline = −0.65, r3 months = −0.60, and r6 months = −0.66 respectively, p <0.001) and mfERG amplitudes of the three innermost rings (rbaseline = −0.29, p = 0.042, r3 months = −0.43, p = 0.003 and r6 months = −0.31, p = 0.042). The VA cutoff for a fixation area less than 5 deg2 (approximately the central hexagon) was 65, 77, and 68 ETDRS letters (corresponding a maximal Snellen equivalent of 0.31) at baseline, 3 and 6 months, respectively. Conclusions: MfERG amplitudes in recordings of nAMD patients are at substantial risk of being reduced due to poor fixation as a large number of patients may use a fixation area of more than 5 deg2. Fixation monitoring during recording as well as interpretation of results should be performed with care, especially in patients with poor visual acuity.
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| 37. |
- Petersen, M. W., et al.
(författare)
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Untargeted antifungal therapy in adult patients with complicated intra-abdominal infection : A systematic review
- 2018
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 62:1, s. 6-18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Systematic reviews comparing untargeted antifungal treatment with placebo or no treatment in critically ill patients have provided conflicting results. We aimed to assess patient-important benefits and harms of untargeted antifungal therapy vs. placebo or no treatment in adult patients with complicated intra-abdominal infection. Methods: We conducted a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials assessing untargeted antifungal therapy compared to placebo or no treatment in adults with complicated intra-abdominal infection. We used the Cochrane and GRADE methodologies and exclusively assessed patient-important outcomes. Two independent authors screened trials for eligibility, extracted data and assessed risk of bias. We performed conventional meta-analyses, including sensitivity and subgroup analyses, and trial sequential analysis to assess the risk of random errors and to estimate trial sequential analysis adjusted confidence intervals. Results: We included six trials (1,067 patients) in the review, and four trials reported data on the predefined outcome measures and were included in the meta-analysis. Three of the four trials had high risk of bias. We observed no statistically significant difference in mortality (relative risk 0.58, 95% confidence interval 0.24-1.39) or in any of the other patient-important outcomes between untargeted antifungal treatment and placebo or no treatment (low/very low quality of evidence). Trial sequential analysis demonstrated lack of data and high risk of random errors. Conclusions: The quantity and quality of evidence supporting untargeted antifungal treatment in adult patients with complicated intra-abdominal infection are low to very low with no firm evidence for benefit or harm.
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| 38. |
- Schwanz, Daphne, et al.
(författare)
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Stochastic Assessment of Voltage Unbalance due to Single-Phase-Connected Solar Power
- 2016
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Ingår i: 2016 17th International Conference on Harmonics and Quality of Power. - Piscataway, NJ. - 9781509037926 ; , s. 95-103
-
Konferensbidrag (refereegranskat)abstract
- A stochastic method is presented in this paper to estimate the future voltage unbalance in a low-voltage distribution network with high-penetration of single-phase photovoltaic inverters (PVIs). Location and phase allocation of the PVIs are considered as input parameters for the stochastic simulation. The method has been applied to three different low-voltage networks: two in Sweden and one in Germany. In the Swedish networks, for 6-kW single-phase PVIs, it is likely that the contribution from single-phase photovoltaic inverters to the voltage unbalance exceeds 1%. The 2% value is unlikely to be exceeded. In the German network, for 4.6-kW single-phase PVIs the voltage unbalance is between 1.35% and 2.62%. The risk of high voltage unbalance can be reduced by a combination of controlled distribution over the phases and reduction of the maximum size for a single-phase PVI.
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| 39. |
- Tiukova, Ievgeniia, 1987, et al.
(författare)
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Identification and characterisation of two high-affinity glucose transporters from the spoilage yeast Brettanomyces bruxellensis
- 2019
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Ingår i: FEMS microbiology letters. - : Oxford University Press (OUP). - 0378-1097 .- 1574-6968. ; 366:17
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Tidskriftsartikel (refereegranskat)abstract
- The yeast Brettanomyces bruxellensis (syn. Dekkera bruxellensis) is an emerging and undesirable contaminant in industrial low-sugar ethanol fermentations that employ the yeast Saccharomyces cerevisiae. High-affinity glucose import in B. bruxellensis has been proposed to be the mechanism by which this yeast can outcompete S. cerevisiae. The present study describes the characterization of two B. bruxellensis genes (BHT1 and BHT3) believed to encode putative high-affinity glucose transporters. In vitro-generated transcripts of both genes as well as the S. cerevisiae HXT7 high-affinity glucose transporter were injected into Xenopus laevis oocytes and subsequent glucose uptake rates were assayed using 14C-labelled glucose. At 0.1 mM glucose, Bht1p was shown to transport glucose five times faster than Hxt7p. pH affected the rate of glucose transport by Bht1p and Bht3p, indicating an active glucose transport mechanism that involves proton symport. These results suggest a possible role for BHT1 and BHT3 in the competitive ability of B. bruxellensis.
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| 40. |
- Tranebjærg, Lisbeth, et al.
(författare)
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The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management
- 2018
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Ingår i: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 137:2, s. 111-127
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Tidskriftsartikel (refereegranskat)abstract
- Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS) is a rare clinically distinct syndrome caused by a single dominant missense mutation, c.2452G>A, p.Glu818Lys, in ATP1A3, encoding the neuron-specific alpha subunit of the Na+/K+-ATPase α3. Allelic mutations cause the neurological diseases rapid dystonia Parkinsonism and alternating hemiplegia of childhood, disorders which do not encompass hearing or visual impairment. We present detailed clinical phenotypic information in 18 genetically confirmed patients from 11 families (10 previously unreported) from Denmark, Sweden, UK and Germany indicating a specific type of hearing impairment-auditory neuropathy (AN). All patients were clinically suspected of CAPOS and had hearing problems. In this retrospective analysis of audiological data, we show for the first time that cochlear outer hair cell activity was preserved as shown by the presence of otoacoustic emissions and cochlear microphonic potentials, but the auditory brainstem responses were grossly abnormal, likely reflecting neural dyssynchrony. Poor speech perception was observed, especially in noise, which was beyond the hearing level obtained in the pure tone audiograms in several of the patients presented here. Molecular modelling and in vitro electrophysiological studies of the specific CAPOS mutation were performed. Heterologous expression studies of α3 with the p.Glu818Lys mutation affects sodium binding to, and release from, the sodium-specific site in the pump, the third ion-binding site. Molecular dynamics simulations confirm that the structure of the C-terminal region is affected. In conclusion, we demonstrate for the first time evidence for auditory neuropathy in CAPOS syndrome, which may reflect impaired propagation of electrical impulses along the spiral ganglion neurons. This has implications for diagnosis and patient management. Auditory neuropathy is difficult to treat with conventional hearing aids, but preliminary improvement in speech perception in some patients suggests that cochlear implantation may be effective in CAPOS patients.
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| 41. |
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