| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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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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| 2. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 5. |
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| 6. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 7. |
- Tiegs, Scott D., et al.
(författare)
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Global patterns and drivers of ecosystem functioning in rivers and riparian zones
- 2019
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Ingår i: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
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| 8. |
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| 9. |
- Ander, Fredrik, 1978-, et al.
(författare)
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Does the β-receptor antagonist esmolol have analgesic effects? : A randomised placebo-controlled cross-over study on healthy volunteers undergoing the cold pressor test
- 2018
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Ingår i: European Journal of Anaesthesiology. - : Lippincott Williams & Wilkins. - 0265-0215 .- 1365-2346. ; 35:3, s. 165-172
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Esmolol may attenuate the sympathetic response to pain and reduce postoperative opioid consumption. It is not clear whether esmolol has an analgesic effect per se.OBJECTIVES: The aim of this study was to evaluate the analgesic effect of esmolol in the absence of anaesthetics and opioids. We tested the hypothesis that esmolol would reduce the maximum pain intensity perceived during the cold pressor test (CPT) by 2 points on a 0 to 10 numeric pain rating scale (NRS) compared to placebo.DESIGN: Randomised, placebo-controlled cross-over study.SETTING: Postoperative recovery area, Örebro University Hospital. Study period, November 2013 to February 2014.PARTICIPANTS: Fourteen healthy volunteers. Exclusion criteria included ongoing medication, pregnancy and breastfeeding and participation in other medical trials.INTERVENTIONS: At separate study sessions, participants received interventions: esmolol (0.7 mg kg bolus over 1 min followed by infusion at 10 μg kg min); 0.9% normal saline bolus then remifentanil infusion at 0.2 μg kg min and 0.9% normal saline bolus and infusion according to a random sequence. All infusions were administered over 30 min.MAIN OUTCOME MEASURES: Perceived maximum pain intensity score, pain tolerance and haemodynamic changes during CPT, and occurrence of side-effects to interventions compared to placebo, respectively.RESULTS: Esmolol did not reduce perceived pain intensity or pain tolerance during the CPT. The NRS-max score was similar for esmolol, 8.5 (±1.4) and placebo, 8.4 (±1.3). The mean difference was 0.1 [95% confidence interval (-1.2 to 1.4)], P value equal to 0.83. Remifentanil significantly reduced NRS-max scores, 5.4 (±2.1) compared to placebo, [mean difference -3.1 (95% confidence interval (-4.4 to -1.8)), P < 0.001]. Side-effects were seen with remifentanil but not with esmolol.CONCLUSION: No direct analgesic effect of esmolol could be demonstrated in the present study. The postoperative opioid-sparing effect demonstrated in previous studies, could therefore be secondary to other factors such as avoidance of opioid-induced hyperalgesia, synergy with coadministered opioids or altered pharmacokinetics of those drugs.TRIAL REGISTRATION: European clinical trials database, https://eudract.ema.europa.eu/, EudraCT no. 2011-005780-24.
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| 10. |
- Ander, Fredrik, 1978-, et al.
(författare)
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Effects of Esmolol on the Esophagogastric Junction : A Double-Blind, Randomized, Crossover Study on 14 Healthy Volunteers
- 2017
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Ingår i: Anesthesia and Analgesia. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0003-2999 .- 1526-7598. ; 125:4, s. 1184-1190
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Passive regurgitation may occur throughout the perioperative period, increasing the risk for pulmonary aspiration and postoperative pulmonary complications. Hypnotics and opioids, especially remifentanil, that are used during anesthesia have been shown to decrease the pressure in the esophagogastric junction (EGJ), that otherwise acts as a barrier against passive regurgitation of gastric contents. Esmolol, usually used to counteract tachycardia and hypertension, has been shown to possess properties useful during general anesthesia. Like remifentanil, the beta-1-adrenoreceptor antagonist may be used to attenuate the stress reaction to tracheal intubation and to modify perioperative anesthetic requirements. It may also reduce the need for opioids in the postoperative period. Its action on the EGJ is however unknown. The aim of this trial was to compare the effects of esmolol and remifentanil on EGJ pressures in healthy volunteers, when administrated as single drugs.METHODS: Measurements of EGJ pressures were made in 14 healthy volunteers using high resolution solid-state manometry. Interventions were administered in a randomized sequence and consisted of esmolol that was given IV as a bolus dose of 1 mg/kg followed by an infusion of 10 mu g.kg(-1).minute(-1) over 15 minutes, and remifentanil with target-controlled infusion of 4 ng/mL over 15 minutes. Interventions were separated by a 20-minute washout period. Analyses of EGJ pressures were performed at baseline, and during drug administration at 2 (T2) and 15 minutes (T15). The primary outcome was the inspiratory EGJ augmentation, while the inspiratory and expiratory EGJ pressures were secondary outcomes.RESULTS: There was no effect on inspiratory EGJ augmentation when comparing remifentanil and esmolol (mean difference -4.0 mm Hg [-9.7 to 1.7]; P = .15). In contrast, remifentanil significantly decreased both inspiratory and expiratory pressures compared to esmolol (-12.2 [-18.6 to 5.7]; P = .003 and 8.0 [-13.3 to 2.8]; P = .006).CONCLUSIONS: Esmolol, compared with remifentanil, does not affect EGJ function. This may be an advantage regarding passive regurgitation and esmolol may thus have a role to play in anesthesia where maintenance of EGJ barrier function is of outmost importance.
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