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Sökning: WFRF:(Humphreys E.) > (2020-2024)

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1.
  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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2.
  • Glasbey, JC, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Khatri, C, et al. (författare)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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  • Fenstermacher, M.E., et al. (författare)
  • DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
  • 2022
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
  • Tidskriftsartikel (refereegranskat)abstract
    • DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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  • Brevini, T, et al. (författare)
  • FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
  • 2023
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7950, s. 134-
  • Tidskriftsartikel (refereegranskat)abstract
    • Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.
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9.
  • Helbig, M., et al. (författare)
  • Warming response of peatland CO2 sink is sensitive to seasonality in warming trends
  • 2022
  • Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-6798 .- 1758-678X. ; 12:8, s. 743-749
  • Tidskriftsartikel (refereegranskat)abstract
    • Peatlands have acted as net CO2 sinks over millennia, exerting a global climate cooling effect. Rapid warming at northern latitudes, where peatlands are abundant, can disturb their CO2 sink function. Here we show that sensitivity of peatland net CO2 exchange to warming changes in sign and magnitude across seasons, resulting in complex net CO2 sink responses. We use multiannual net CO2 exchange observations from 20 northern peatlands to show that warmer early summers are linked to increased net CO2 uptake, while warmer late summers lead to decreased net CO2 uptake. Thus, net CO2 sinks of peatlands in regions experiencing early summer warming, such as central Siberia, are more likely to persist under warmer climate conditions than are those in other regions. Our results will be useful to improve the design of future warming experiments and to better interpret large-scale trends in peatland net CO2 uptake over the coming few decades.
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  • Stepniewska, Kasia, et al. (författare)
  • Efficacy of single dose primaquine with artemisinin combination therapy on P. falciparum gametocytes and transmission : A WWARN individual patient meta-analysis.
  • 2020
  • Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 225:7, s. 1215-1226
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy.METHODS: An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected.RESULTS: In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08-0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.CONCLUSION: Primaquine's transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.
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11.
  • 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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  • Figlioli, G, et al. (författare)
  • FANCM missense variants and breast cancer risk: a case-control association study of 75,156 European women
  • 2023
  • Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 31:5, s. 578-587
  • Tidskriftsartikel (refereegranskat)abstract
    • Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry. Sixteen common MVs were tested individually; the remaining rare 673 MVs were tested by burden analyses considering their position and pathogenicity score. We also conducted a meta-analysis of our results and those from published studies. We did not find evidence for association for any of the 16 variants individually tested. The rare MVs were significantly associated with increased risk of ER-negative breast cancer by burden analysis comparing familial cases to controls (OR = 1.48; 95% CI 1.07–2.04; P = 0.017). Higher ORs were found for the subgroup of MVs located in functional domains or predicted to be pathogenic. The meta-analysis indicated that FANCM MVs overall are associated with breast cancer risk (OR = 1.22; 95% CI 1.08–1.38; P = 0.002). Our results support the definition from previous analyses of FANCM as a moderate-risk breast cancer gene and provide evidence that FANCM MVs could be low/moderate risk factors for ER-negative and TNBC subtypes. Further genetic and functional analyses are necessary to clarify better the increased risks due to FANCM MVs.
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  • Mansoor, Rashid, et al. (författare)
  • Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
  • 2022
  • Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPlasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.MethodsIndividual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7.ResultsA total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001).ConclusionsIn patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
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  • Quinatoa, Daysi, et al. (författare)
  • The first ground-based detection of the 752 GHz water line in local ultraluminous infrared galaxies using APEX-SEPIA
  • 2024
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 527:3, s. 6321-6331
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the first ground-based detection of the water line p-H2O (211-202) at 752.033 GHz in three z < 0.08 ultraluminous infrared galaxies (ULIRGs): IRAS 06035-7102, IRAS 17207-0014, and IRAS 09022-3615. Using the Atacama Pathfinder EXperiment (APEX), with its Swedish-ESO PI Instrument for APEX (SEPIA) band-9 receiver, we detect this H2O line with overall signal-to-noise ratios of 8-10 in all three galaxies. Notably, this is the first detection of this line in IRAS 06035-7102. Our new APEX-measured fluxes, between 145 and 705 Jy km s-1, are compared with previous values taken from Herschel SPIRE FTS. We highlight the great capabilities of APEX for resolving the H2O line profiles with high spectral resolutions while also improving by a factor of two the significance of the detection within moderate integration times. While exploring the correlation between the p-H2O(211-202) and the total infrared luminosity, our galaxies are found to follow the trend at the bright end of the local ULIRG's distribution. The p-H2O(211-202) line spectra are compared to the mid-J CO and HCN spectra, and dust continuum previously observed with ALMA. In the complex interacting system IRAS 09022-3615, the profile of the water emission line is offset in velocity with respect to the ALMA CO(J = 4-3) emission. For IRAS 17207-0014 and IRAS 06035-7102, the profiles between the water line and the CO lines are spectroscopically aligned. This pilot study demonstrates the feasibility of directly conducting ground-based high-frequency observations of this key water line, opening the possibility of detailed follow-up campaigns to tackle its nature.
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  • Bergman, Per, 1960, et al. (författare)
  • Submillimetre water masers at 437, 439, 471, and 474 GHz towards evolved stars: APEX observations and radiative transfer modelling*
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 638
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. Here we aim to characterise submillimetre water masers at 437, 439, 471, and 474 GHz towards a sample of evolved stars. Methods. We used the Atacama Pathfinder Experiment (APEX(1)) to observe submillimetre water transitions and the CO (4-3) line towards 11 evolved stars. The sample included semi-regular and Mira variables, plus a red supergiant star. We performed radiative transfer modelling for the water masers. We also used the CO observations to determine mass loss rates for the stars. Results. From the sample of 11 evolved stars, 7 display one or more of the masers at 437, 439, 471, and 474 GHz. We therefore find that these masers are common in evolved star circumstellar envelopes. The fact that the maser lines are detected near the stellar velocity indicates that they are likely to originate from the inner circumstellar envelopes of our targets. We tentatively link the presence of masers to the degree of variability of the target star, that is, masers are more likely to be present in Mira variables than in semi-regular variables. We suggest that this indicates the importance of strong shocks in creating the necessary conditions for the masers. Typically, the 437 GHz line is the strongest maser line observed among those studied here. We cannot reproduce the above finding in our radiative transfer models. In general, we find that maser emission is very sensitive to dust temperature in the lines studied here. To produce strong maser emission, the dust temperature must be significantly lower than the gas kinetic temperature. In addition to running grids of models in order to determine the optimum physical conditions for strong masers in these lines, we performed smooth wind modelling for which we cannot reproduce the observed line shapes. This also suggests that the masers must originate predominantly from the inner envelopes.
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  • Berner, Logan T., et al. (författare)
  • The Arctic plant aboveground biomass synthesis dataset
  • 2024
  • Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.
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  • Callen, Michael, et al. (författare)
  • COVID-19 vaccine acceptance and hesitancy in low- and middle-income countries
  • 2021
  • Ingår i: Nature Medicine. - : Springer Nature. - 1546-170X .- 1078-8956. ; 27:8, s. 1385-1394
  • Tidskriftsartikel (refereegranskat)abstract
    • Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs. © 2021, The Author(s).
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  • Facchini, S., et al. (författare)
  • Resolved ALMA observations of water in the inner astronomical units of the HL Tau disk
  • 2024
  • Ingår i: Nature Astronomy. - 2397-3366. ; 8:5, s. 587-595
  • Tidskriftsartikel (refereegranskat)abstract
    • The water molecule is a key ingredient in the formation of planetary systems, with the water snowline being a favourable location for the growth of massive planetary cores. Here we present Atacama Large Millimeter/submillimeter Array data of the ringed protoplanetary disk orbiting the young star HL Tauri that show centrally peaked, bright emission arising from three distinct transitions of the main water isotopologue (H216O). The spatially and spectrally resolved water content probes gas in a thermal range down to the water sublimation temperature. Our analysis implies a stringent lower limit of 3.7 Earth oceans of water vapour available within the inner 17 astronomical units of the system. We show that our observations are limited to probing the water content in the atmosphere of the disk, due to the high dust column density and absorption, and indicate that the main water isotopologue is the best tracer to spatially resolve water vapour in protoplanetary disks.
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