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1.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Richards, Stephen, et al. (författare)
  • Genome Sequence of the Pea Aphid Acyrthosiphon pisum
  • 2010
  • Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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  • Bolton, Kelly L., et al. (författare)
  • Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer
  • 2012
  • Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 307:4, s. 382-390
  • Tidskriftsartikel (refereegranskat)abstract
    • Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P<.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P<.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P<.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P<.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390
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  • Fiddaman, Steven R., et al. (författare)
  • Ancient chicken remains reveal the origins of virulence in Marek's disease virus
  • 2023
  • Ingår i: Science (New York, N.Y.). - 1095-9203. ; 382:6676, s. 1276-1281
  • Tidskriftsartikel (refereegranskat)abstract
    • The pronounced growth in livestock populations since the 1950s has altered the epidemiological and evolutionary trajectory of their associated pathogens. For example, Marek's disease virus (MDV), which causes lymphoid tumors in chickens, has experienced a marked increase in virulence over the past century. Today, MDV infections kill >90% of unvaccinated birds, and controlling it costs more than US$1 billion annually. By sequencing MDV genomes derived from archeological chickens, we demonstrate that it has been circulating for at least 1000 years. We functionally tested the Meq oncogene, one of 49 viral genes positively selected in modern strains, demonstrating that ancient MDV was likely incapable of driving tumor formation. Our results demonstrate the power of ancient DNA approaches to trace the molecular basis of virulence in economically relevant pathogens.
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  • Fuqua, Joshua L, et al. (författare)
  • Dynamic changes in dopamine neuron function after DNSP-11 treatment: Effects in vivo and increased ERK 1/2 phosphorylation in vitro.
  • 2014
  • Ingår i: Peptides. - : Elsevier BV. - 1873-5169 .- 0196-9781. ; 54:Jan 7, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Glial cell-line derived neurotrophic factor (GDNF) has demonstrated robust effects on dopamine (DA) neuron function and survival. A post-translational processing model of the human GDNF proprotein theorizes the formation of smaller, amidated peptide(s) from the proregion that exhibit neurobiological function, including an 11-amino-acid peptide named dopamine neuron stimulating peptide-11 (DNSP-11). A single treatment of DNSP-11 was delivered to the substantia nigra in the rat to investigate effects on DA-neuron function. Four weeks after treatment, potassium (K+) and d-amphetamine evoked DA release were studied in the striatum using microdialysis. There were no significant changes in DA-release after DNSP-11 treatment determined by microdialysis. Dopamine release was further examined in discrete regions of the striatum using high-speed chronoamperometry at 1-, 2-, and 4-weeks after DNSP-11 treatment. Two weeks after DNSP-11 treatment, potassium-evoked DA release was increased in specific subregions of the striatum. However, spontaneous locomotor activity was unchanged by DNSP-11 treatment. In addition, we show that a single treatment of DNSP-11 in the MN9D dopaminergic neuronal cell line results in phosphorylation of ERK1/2, which suggests a novel cellular mechanism responsible for increases in DA function.
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  • Kunder, Andrea, et al. (författare)
  • THE RADIAL VELOCITY EXPERIMENT (RAVE) : FIFTH DATA RELEASE
  • 2017
  • Ingår i: The Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 153:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Data Release 5 (DR5) of the Radial Velocity Experiment (RAVE) is the fifth data release from a magnitude-limited (9 < I < 12) survey of stars randomly selected in the Southern Hemisphere. The RAVE medium-resolution spectra (R ∼ 7500) covering the Ca-triplet region (8410-8795 A) span the complete time frame from the start of RAVE observations in 2003 to their completion in 2013. Radial velocities from 520,781 spectra of 457,588 unique stars are presented, of which 255,922 stellar observations have parallaxes and proper motions from the Tycho-Gaia astrometric solution in Gaia DR1. For our main DR5 catalog, stellar parameters (effective temperature, surface gravity, and overall metallicity) are computed using the RAVE DR4 stellar pipeline, but calibrated using recent K2 Campaign 1 seismic gravities and Gaia benchmark stars, as well as results obtained from high-resolution studies. Also included are temperatures from the Infrared Flux Method, and we provide a catalog of red giant stars in the dereddened color - (J Ks) 0 interval (0.50, 0.85) for which the gravities were calibrated based only on seismology. Further data products for subsamples of the RAVE stars include individual abundances for Mg, Al, Si, Ca, Ti, Fe, and Ni, and distances found using isochrones. Each RAVE spectrum is complemented by an error spectrum, which has been used to determine uncertainties on the parameters. The data can be accessed via the RAVE Web site or the VizieR database.
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  • Reisch, Lucia A., et al. (författare)
  • Mitigating climate change via food consumption and food waste: A systematic map of behavioral interventions
  • 2021
  • Ingår i: Journal of Cleaner Production. - : Elsevier. - 1879-1786 .- 0959-6526. ; 279, s. 1-16
  • Tidskriftsartikel (refereegranskat)abstract
    • Demand-side policies for mitigating climate change based on behavioral insights are gaining increased attention in research and practice. Here we describe a systematic map that catalogues existing research on behaviorally informed interventions targeting changes in consumer food consumption and food waste behavior. The purpose is to gain an overview of research foci and gaps, providing an evidence base for deeper analysis. In terms of food consumption, we focus on animal protein (meat, fish, dairy, and eggs) and its substitutes. The map follows the standards for evidence synthesis from the Collaboration for Environmental Evidence (CEE) as well as the RepOrting Standards for Systematic Evidence Syntheses (ROSES). We identified 49 articles including 56 separate studies, as well as 18 literature reviews. We find a variety of study designs with a focus on canteen and restaurant studies as well as a steep increase of publications since 2016. We create an interactive evidence atlas that plots these studies across geographical space. Here, we find a concentration of research in the Anglo-Saxon world. Most studies follow multi-intervention designs and focus on actual food consumption behavior, fewer on food waste behavior. We identify knowledge clusters amenable for a systematic review focusing on the effectiveness of these interventions, namely: priming, disclosure, defaults, social norms, micro-environment changes, and ease of use. The systematic map highlights knowledge gaps, where more primary research is needed and evidence cannot support policy; it identifies knowledge clusters, where sufficient studies exist but there is a lack of clarity over effectiveness, and so full synthesis can be conducted rapidly; finally, it reveals patterns in research methods that can highlight best practices and issues with methodology that can support the improvement of primary evidence production and mitigation of research waste. To the best of our knowledge, this is the first systematic study mapping this specific area.
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  • Schoerck, T, et al. (författare)
  • The stellar content of the Hamburg/ESO survey V. The metallicity distribution function of the Galactic halo
  • 2009
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 507:2, s. 817-832
  • Tidskriftsartikel (refereegranskat)abstract
    • We determine the metallicity distribution function (MDF) of the Galactic halo by means of a sample of 1638 metal-poor stars selected from the Hamburg/ESO objective-prism survey (HES). The sample was corrected for minor biases introduced by the strategy for spectroscopic follow-up observations of the metal-poor candidates, namely "best and brightest stars first". Comparison of the metallicities [Fe/H] of the stars determined from moderate-resolution (i.e., R similar to 2000) follow-up spectra with results derived from abundance analyses based on high-resolution spectra (i.e., R > 20 000) shows that the [Fe/H] estimates used for the determination of the halo MDF are accurate to within 0.3 dex, once highly C-rich stars are eliminated. We determined the selection function of the HES, which must be taken into account for a proper comparison between the HES MDF with MDFs of other stellar populations or those predicted by models of Galactic chemical evolution. The latter show a reasonable agreement with the overall shape of the HES MDF for [Fe/H] > -3.6, but only a model of Salvadori et al. (2007) with a critical metallicity for low-mass star formation of Z(cr) = 10(-3.4) Z(circle dot) reproduces the sharp drop at [Fe/H] similar to -3.6 present in the HES MDF. Although currently about ten stars at [Fe/H] < -3.6 are known, the evidence for the existence of a tail of the halo MDF extending to [Fe/H] similar to -5.5 is weak from the sample considered in this paper, because it only includes two stars [Fe/H] < -3.6. Therefore, a comparison with theoretical models has to await larger statistically complete and unbiased samples. A comparison of the MDF of Galactic globular clusters and of dSph satellites to the Galaxy shows qualitative agreement with the halo MDF, derived from the HES, once the selection function of the latter is included. However, statistical tests show that the differences between these are still highly significant.
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  • Baigent, Colin, et al. (författare)
  • The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection) : a randomised placebo-controlled trial
  • 2011
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 377:9784, s. 2181-2192
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and I SRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0.85 mmol/L (SE 0.02; with about two-thirds compliance) during a median follow-up of 4.9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11.3%] simvastatin plus ezetimibe vs 619 [13.4%] placebo; rate ratio [RR] 0.83, 95% CI 0.74-0.94; log-rank p=0.0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4.6%] vs 230 [5.0%]; RR 0.92,95% CI 0.76-1.11; p=0.37) and there were significant reductions in non-haemorrhagic stroke (131 [2.8%] vs 174 [3.8%]; RR 0.75,95% CI 0.60-0.94; p=0.01) and arterial revascularisation procedures (284 [6.1%] vs 352 [7.6%]; RR 0.79, 95% CI 0.68-0.93; p=0.0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0.2%] vs 5 [0.1%]). There was no evidence of excess risks of hepatitis (21 [0.5%] vs 18 [0.4%]), gallstones (106 [2.3%] vs 106 [2.3%]), or cancer (438 [9.4%] vs 439 [9.5%], p=0.89) and there was no significant excess of death from any non-vascular cause (668 [14.4%] vs 612 [13.2%], p=0.13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease.
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  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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  • Bellomo, R, et al. (författare)
  • Femoral Access and Delivery of Continuous Renal Replacement Therapy Dose
  • 2016
  • Ingår i: Blood purification. - : S. Karger AG. - 1421-9735 .- 0253-5068. ; 41:1-3, s. 11-17
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Aims:</i></b> The study aims to describe the use of dialysis catheters in critically ill patients treated with continuous renal replacement therapy (CRRT) and to study the impact of femoral versus non-femoral access on CRRT dose. <b><i>Methods:</i></b> Statistical analysis and predictive modelling of data from the Randomized Evaluation of Normal vs. Augmented Level renal replacement therapy trial. <b><i>Results:</i></b> The femoral vein was the first access site in 937 (67%) of 1,399 patients. These patients had higher Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores (p = 0.009) and lower pH (p < 0.001) but similar mortality to patients with non-femoral access (44 vs. 45%; p = 0.63). Lower body weight was independently associated with femoral access placement (OR 0.97, 95% CI 0.96-0.98). Femoral access was associated with a 1.03% lower CRRT dose (p = 0.05), but a 4.20% higher dose was achieved with 13.5 Fr catheters (p = 0.03). <b><i>Conclusions:</i></b> Femoral access was preferred in lighter and sicker patients. Catheter gauge had greater impact than catheter site in CRRT dose delivery. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=439581.
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  • Bootpetch, TC, et al. (författare)
  • Multi-omic studies on missense PLG variants in families with otitis media
  • 2020
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 15035-
  • Tidskriftsartikel (refereegranskat)abstract
    • Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial α-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.
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  • Janson, Staffan, 1945-, et al. (författare)
  • How can we improve child health services?
  • 2011
  • Ingår i: The BMJ. - : BMJ Books. - 1756-1833. ; 342, s. 901-904
  • Tidskriftsartikel (refereegranskat)abstract
    • Western European health systems are not keeping pace with changes in child health needs. Non-communicable diseases are increasingly common causes of childhood illness and death. Countries are responding to changing needs by adapting child health services in different ways and useful insights can be gained through comparison, especially because some have better outcomes, or have made more progress, than others. Although overall child health has improved throughout Europe, wide inequities remain. Health services and social and cultural determinants contribute to differences in health outcomes. Improvement of child health and reduction of suffering are achievable goals. Development of systems more responsive to evolving child health needs is likely to necessitate reconfiguring of health services as part of a whole-systems approach to improvement of health. Chronic care services and first-contact care systems are important aspects. The Swedish and Dutch experiences of development of integrated systems emphasise the importance of supportive policies backed by adequate funding. France, the UK, Italy, and Germany offer further insights into chronic care services in different health systems. First-contact care models and the outcomes they deliver are highly variable. Comparisons between systems are challenging. Important issues emerging include the organisation of first-contact models, professional training, arrangements for provision of out-of-hours services, and task-sharing between doctors and nurses. Flexible first-contact models in which child health professionals work closely together could offer a way to balance the need to provide expertise with ready access. Strategies to improve child health and health services in Europe necessitate a whole-systems approach in three interdependent systems—practice (chronic care models, first-contact care, competency standards for child health professionals), plans (child health indicator sets, reliable systems for capture and analysis of data, scale-up of child health research, anticipation of future child health needs), and policy (translation of high-level goals into actionable policies, open and transparent accountability structures, political commitment to delivery of improvements in child health and equity throughout Europe).
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  • O'Brien, Z, et al. (författare)
  • Higher versus Lower Continuous Renal Replacement Therapy Intensity in Critically ill Patients with Liver Dysfunction
  • 2018
  • Ingår i: Blood purification. - : S. Karger AG. - 1421-9735 .- 0253-5068. ; 45:1-3, s. 36-43
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Aims:</i></b> To study the association between higher versus lower continuous renal replacement therapy (CRRT) intensity and mortality in critically ill patients with combined acute kidney injury and liver dysfunction. <b><i>Methods:</i></b> Post-hoc analysis of patients with liver dysfunction (Sequential Organ Failure Assessment liver score ≥2 or diagnosis of liver failure/transplant) included in the Randomized Evaluation of Normal versus Augmented Level renal replacement therapy (RENAL) trial. <b><i>Results:</i></b> Of 444 patients, 210 (47.3%) were randomized to higher intensity (effluent flow 40 mL/kg/h) and 234 (52.7%) to lower intensity (effluent flow 25 mL/kg/h) therapy. Overall, 79 and 86% of prescribed effluent flow was delivered in the higher-intensity and lower-intensity groups, respectively (<i>p</i> < 0.001). In total, 113 (54.1%) and 120 (51.3%) patients died in each group. On multivariable Cox regression analysis, we found no independent association between higher CRRT intensity and mortality (HR 0.93, 95% CI 0.70-1.24; <i>p</i> = 0.642). <b><i>Conclusions:</i></b> In RENAL patients with liver dysfunction, higher CRRT intensity was not associated with reduced mortality.
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