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- Ederle, Joerg, et al.
(author)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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In: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Journal article (peer-reviewed)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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5. |
- Meyer, H., et al.
(author)
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Overview of physics results from MAST towards ITER/DEMO and the MAST Upgrade
- 2013
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:10, s. 104008-
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Journal article (peer-reviewed)abstract
- New diagnostic, modelling and plant capability on the Mega Ampere Spherical Tokamak (MAST) have delivered important results in key areas for ITER/DEMO and the upcoming MAST Upgrade, a step towards future ST devices on the path to fusion currently under procurement. Micro-stability analysis of the pedestal highlights the potential roles of micro-tearing modes and kinetic ballooning modes for the pedestal formation. Mitigation of edge localized modes (ELM) using resonant magnetic perturbation has been demonstrated for toroidal mode numbers n = 3, 4, 6 with an ELM frequency increase by up to a factor of 9, compatible with pellet fuelling. The peak heat flux of mitigated and natural ELMs follows the same linear trend with ELM energy loss and the first ELM-resolved T-i measurements in the divertor region are shown. Measurements of flow shear and turbulence dynamics during L-H transitions show filaments erupting from the plasma edge whilst the full flow shear is still present. Off-axis neutral beam injection helps to strongly reduce the redistribution of fast-ions due to fishbone modes when compared to on-axis injection. Low-k ion-scale turbulence has been measured in L-mode and compared to global gyro-kinetic simulations. A statistical analysis of principal turbulence time scales shows them to be of comparable magnitude and reasonably correlated with turbulence decorrelation time. T-e inside the island of a neoclassical tearing mode allow the analysis of the island evolution without assuming specific models for the heat flux. Other results include the discrepancy of the current profile evolution during the current ramp-up with solutions of the poloidal field diffusion equation, studies of the anomalous Doppler resonance compressional Alfven eigenmodes, disruption mitigation studies and modelling of the new divertor design for MAST Upgrade. The novel 3D electron Bernstein synthetic imaging shows promising first data sensitive to the edge current profile and flows.
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6. |
- de Graauw, Th., et al.
(author)
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The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI)
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L6-
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Journal article (peer-reviewed)abstract
- Aims: This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI) that was launched onboard ESA's Herschel Space Observatory in May 2009. Methods: The instrument is a set of 7 heterodyne receivers that are electronically tuneable, covering 480-1250 GHz with SIS mixers and the 1410-1910 GHz range with hot electron bolometer (HEB) mixers. The local oscillator (LO) subsystem comprises a Ka-band synthesizer followed by 14 chains of frequency multipliers and 2 chains for each frequency band. A pair of auto-correlators and a pair of acousto-optical spectrometers process the two IF signals from the dual-polarization, single-pixel front-ends to provide instantaneous frequency coverage of 2 × 4 GHz, with a set of resolutions (125 kHz to 1 MHz) that are better than 0.1 km s-1. Results: After a successful qualification and a pre-launch TB/TV test program, the flight instrument is now in-orbit and completed successfully the commissioning and performance verification phase. The in-orbit performance of the receivers matches the pre-launch sensitivities. We also report on the in-orbit performance of the receivers and some first results of HIFI's operations. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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7. |
- Pulit, SL, et al.
(author)
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Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.
- 2016
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In: The Lancet. Neurology. - 1474-4465. ; 15:2, s. 174-84
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Journal article (peer-reviewed)abstract
- The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes.To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16851 cases with state-of-the-art phenotyping data and 32473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20941 cases and 364736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis.We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50×10(-8); joint OR 1·19, 1·12-1·26, p=1·30×10(-9)). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26×10(-19); joint OR 1·37, 1·30-1·45, p=2·79×10(-32)) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93×10(-7); joint OR 1·17, 1·11-1·23, p=2·29×10(-10)) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50×10(-8); joint OR 1·24, 1·15-1·33, p=4·52×10(-9)) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82×10(-8); joint OR 1·17, 1·11-1·23, p=2·92×10(-9)). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed.Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke.US National Institute of Neurological Disorders and Stroke, National Institutes of Health.
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- Roelfsema, P. R., et al.
(author)
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In-orbit performance of Herschel-HIFI
- 2012
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537
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Journal article (peer-reviewed)abstract
- Aims: In this paper the calibration and in-orbit performance of the Heterodyne Instrument for the Far-Infrared (HIFI) is described.Methods: The calibration of HIFI is based on a combination of ground and in-flight tests. Dedicated ground tests to determine those instrument parameters that can only be measured accurately using controlled laboratory stimuli were carried out in the instrument level test (ILT) campaign. Special in-flight tests during the commissioning phase (CoP) and performance verification (PV) allowed the determination of the remaining instrument parameters. The various instrument observing modes, as specified in astronomical observation templates (AOTs), were validated in parallel during PV by observing selected celestial sources.Results: The initial calibration and in-orbit performance of HIFI has been established. A first estimate of the calibration budget is given. The overall in-flight instrument performance agrees with the original specification. Issues remain at only a few frequencies. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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10. |
- Lamb, G. P., et al.
(author)
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Short GRB 160821B : A Reverse Shock, a Refreshed Shock, and a Well-sampled Kilonova
- 2019
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 883:1
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Journal article (peer-reviewed)abstract
- We report our identification of the optical afterglow and host galaxy of the short-duration gamma-ray burst sGRB 160821B. The spectroscopic redshift of the host is z = 0.162, making it one of the lowest redshift short-duration gamma-ray bursts (sGRBs) identified by Swift. Our intensive follow-up campaign using a range of ground-based facilities as well as Hubble Space Telescope, XMM-Newton, and Swift, shows evidence for a late-time excess of optical and near-infrared emission in addition to a complex afterglow. The afterglow light curve at X-ray frequencies reveals a narrow jet, theta(j) similar to 1.9(-0.03)(+0.10) deg, that is refreshed at >1 day post-burst by a slower outflow with significantly more energy than the initial outflow that produced the main GRB. Observations of the 5 GHz radio afterglow shows a reverse shock into a mildly magnetized shell. The optical and near-infrared excess is fainter than AT2017gfo associated with GW170817, and is well explained by a kilonova with dynamic ejecta mass M-dyn = (1.0 +/- 0.6) x 10(-3) M-circle dot and a secular (post-merger) ejecta mass with M-pm = (1.0 +/- 0.6) x 10(-2) M-circle dot, consistent with a binary neutron star merger resulting in a short-lived massive neutron star. This optical and near-infrared data set provides the best-sampled kilonova light curve without a gravitational wave trigger to date.
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11. |
- Wannigama, D. L., et al.
(author)
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COVID-19 monitoring with sparse sampling of sewered and non-sewered wastewater in urban and rural communities
- 2023
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In: Iscience. ; 26:7
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Journal article (peer-reviewed)abstract
- Equitable SARS-CoV-2 surveillance in low-resource communities lacking centralized sewers is critical as wastewater-based epidemiology (WBE) progresses. However, large-scale studies on SARS-CoV-2 detection in wastewater from low-and middle-income countries is limited because of economic and technical reasons. In this study, wastewater samples were collected twice a month from 186 urban and rural subdistricts in nine provinces of Thailand mostly having decentralized and non-sewered sanitation infrastructure and analyzed for SARS-CoV-2 RNA variants using allele-specific RT-qPCR. Wastewater SARS-CoV-2 RNA concentration was used to estimate the real-time incidence and time-varying effective reproduction number (Re). Results showed an increase in SARS-CoV-2 RNA concentrations in wastewater from urban and rural areas 14-20 days earlier than infected individuals were officially reported. It also showed that community/food markets were ''hot spots'' for infected people. This approach offers an opportunity for early detection of transmission surges, allowing preparedness and potentially mitigating significant outbreaks at both spatial and temporal scales.
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13. |
- Hilton, J., et al.
(author)
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α -spectroscopy studies of the new nuclides Pt 165 and Hg 170
- 2019
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In: Physical Review C. - 2469-9985. ; 100:1
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Journal article (peer-reviewed)abstract
- The new nuclides Pt165 and Hg170 were produced in the reactions Mo92(Kr78,5n) and Ru96(Kr78,4n) at bombarding energies of 418 MeV and 390 MeV, respectively. For Hg170 an α-particle energy of Eα=7590(30)keV and half-life of t1/2=0.08-0.04+0.40ms were deduced, while for Pt165 the corresponding values were 7272(14) keV and 0.26-0.09+0.26ms. Comparison of the reduced α-decay widths with systematics indicates that both α decays are unhindered. Although combining the measured α-decay Q values with extrapolated masses suggests that both new nuclides are unbound to two-proton emission by more than 1 MeV, their α-decay half-lives are too short for this decay mode to compete. Improved data were also obtained for Pt166,167, produced via the Ru96(Kr78,α4n) and Ru96(Kr78,α3n) reactions at bombarding energies of 390 MeV and 418 MeV.
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14. |
- Pilla, Rachel M., et al.
(author)
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Deeper waters are changing less consistently than surface waters in a global analysis of 102 lakes
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Globally, lake surface water temperatures have warmed rapidly relative to air temperatures, but changes in deepwater temperatures and vertical thermal structure are still largely unknown. We have compiled the most comprehensive data set to date of long-term (1970–2009) summertime vertical temperature profiles in lakes across the world to examine trends and drivers of whole-lake vertical thermal structure. We found significant increases in surface water temperatures across lakes at an average rate of + 0.37 °C decade−1, comparable to changes reported previously for other lakes, and similarly consistent trends of increasing water column stability (+ 0.08 kg m−3 decade−1). In contrast, however, deepwater temperature trends showed little change on average (+ 0.06 °C decade−1), but had high variability across lakes, with trends in individual lakes ranging from − 0.68 °C decade−1 to + 0.65 °C decade−1. The variability in deepwater temperature trends was not explained by trends in either surface water temperatures or thermal stability within lakes, and only 8.4% was explained by lake thermal region or local lake characteristics in a random forest analysis. These findings suggest that external drivers beyond our tested lake characteristics are important in explaining long-term trends in thermal structure, such as local to regional climate patterns or additional external anthropogenic influences.
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15. |
- Valdes-Marquez, E., et al.
(author)
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Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study
- 2019
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:11
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Journal article (peer-reviewed)abstract
- Objective To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 x 10(-8)). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 x 10(-3)) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 x 10(-3)) when compared with that for CHD. In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
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16. |
- Wannigama, D. L., et al.
(author)
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Multiple traces of monkeypox detected in non-sewered wastewater with sparse sampling from a densely populated metropolitan area in Asia
- 2023
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In: SCIENCE OF THE TOTAL ENVIRONMENT. - : Elsevier BV. - 0048-9697. ; 858
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Journal article (peer-reviewed)abstract
- The monkeypox virus is excreted in the feces of infected individuals. Therefore, there is an interest in using viral load detection in wastewater for sentinel early surveillance at a community level and as a complementary approach to syndromic surveillance. We collected wastewater from 63 sewered and non-sewered locations in Bangkok city center between May and August 2022. Monkeypox viral DNA copy numbers were quantified using real-time polymerase chain reaction (PCR) and confirmed positive by Sanger sequencing. Monkeypox viral DNA was first detected in waste-water from the second week of June 2022, with a mean copy number of 16.4 copies/ml (n = 3). From the first week of July, the number of viral DNA copies increased to a mean copy number of 45.92 copies/ml. Positive samples were Sanger sequenced and confirmed the presence of the monkeypox virus. Our study is the first to detect monkeypox viral DNA in wastewater from various locations within Thailand. Results suggest that this could be a complementary source for detecting viral DNA and predicting upcoming outbreaks.
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17. |
- Willeit, P., et al.
(author)
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Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients
- 2020
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In: Circulation. - 1524-4539. ; 142:7, s. 621-642
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Journal article (peer-reviewed)abstract
- BACKGROUND: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.
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18. |
- Axfors, Cathrine, et al.
(author)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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In: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Research review (peer-reviewed)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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19. |
- Burdett, S., et al.
(author)
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Adjuvant chemotherapy for resected early-stage non-small cell lung cancer
- 2015
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In: Cochrane Database of Systematic Reviews. - 1469-493X. ; :3
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Research review (peer-reviewed)abstract
- Background To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC), we performed two systematic reviews andmeta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010. Objectives To compare, in terms of overall survival, time to locoregional recurrence, time to distant recurrence and recurrence-free survival: A. Surgery versus surgery plus adjuvant chemotherapy B. Surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy in patients with histologically diagnosed early stage NSCLC. (2) To investigate whether or not predefined patient subgroups benefit more or less from cisplatin-based chemotherapy in terms of survival. Search methods We supplemented MEDLINE and CANCERLIT searches (1995 to December 2013) with information from trial registers, hand-searching relevant meeting proceedings and by discussion with trialists and organisations. Selection criteria We included trials of a) surgery versus surgery plus adjuvant chemotherapy; and b) surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy, provided that they randomised NSCLC patients using a method which precluded prior knowledge of treatment assignment. Data collection and analysis We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. Data from all patients were sought from those responsible for the trial. We obtained updated individual participant data (IPD) on survival, and date of last follow-up, as well as details of treatment allocated, date of randomisation, age, sex, histological cell type, stage, and performance status. To avoid potential bias, we requested information for all randomised patients, including those excluded from the investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. For trials using cisplatin-based regimens, we carried out subgroup analyses by age, sex, histological cell type, tumour stage, and performance status. Main results We identified 35 trials evaluating surgery plus adjuvant chemotherapy versus surgery alone. IPD were available for 26 of these trials and our analyses are based on 8447 participants (3323 deaths) in 34 trial comparisons. There was clear evidence of a benefit of adding chemotherapy after surgery (hazard ratio (HR)= 0.86, 95% confidence interval (CI)= 0.81 to 0.92, p< 0.0001), with an absolute increase in survival of 4% at five years. We identified 15 trials evaluating surgery plus radiotherapy plus chemotherapy versus surgery plus radiotherapy alone. IPD were available for 12 of these trials and our analyses are based on 2660 participants (1909 deaths) in 13 trial comparisons. There was also evidence of a benefit of adding chemotherapy to surgery plus radiotherapy (HR= 0.88, 95% CI= 0.81 to 0.97, p= 0.009). This represents an absolute improvement in survival of 4% at five years. For both meta-analyses, we found similar benefits for recurrence outcomes and there was little variation in effect according to the type of chemotherapy, other trial characteristics or patient subgroup. We did not undertake analysis of the effects of adjuvant chemotherapy on quality of life and adverse events. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable. We considered the risk of bias in the included trials to be low. Authors' conclusions Results from 47 trial comparisons and 11,107 patients demonstrate the clear benefit of adjuvant chemotherapy for these patients, irrespective of whether chemotherapy was given in addition to surgery or surgery plus radiotherapy. This is the most up-to-date and complete systematic review and individual participant data (IPD) meta-analysis that has been carried out.
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20. |
- Joss, D. T., et al.
(author)
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Evolving collective structures in the transitional nuclei W-162 and W-164
- 2016
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In: PHYSICAL REVIEW C. - : American Physical Society. - 2469-9985. ; 93:2
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Journal article (peer-reviewed)abstract
- Excited states in the neutron-deficient nuclides(74)(162)W(88) and W-164(74)90 were investigated by using the gamma-ray spectrometer Jurogam. A change in structure is apparent from the first rotational alignments in W-162 and W-164, whose rotationally aligned bands are interpreted as nu(h(9/2))(2) and nu(i(13/2))(2) configurations, respectively. The level schemes have been extended using recoil (-decay) correlations with the observation of excited collective structures. Configuration assignments have been made on the basis of comparisons of the deduced aligned angular momentum, as a function of rotational frequency, with the predictions of the cranked shell model.
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21. |
- O’Reilly, Catherine M., et al.
(author)
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Rapid and highly variable warming of lake surface waters around the globe
- 2015
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 42:24
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Journal article (peer-reviewed)abstract
- In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade−1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors—from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade−1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade−1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes.
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22. |
- Pilla, Rachel M., et al.
(author)
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Global data set of long-term summertime vertical temperature profiles in 153 lakes
- 2021
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In: Scientific Data. - : Springer Nature. - 2052-4463. ; 8:1
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Journal article (peer-reviewed)abstract
- Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change.
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23. |
- Scherer, SW, et al.
(author)
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Human chromosome 7: DNA sequence and biology
- 2003
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 300:5620, s. 767-772
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Journal article (peer-reviewed)abstract
- DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.
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25. |
- Shein, A. M. S., et al.
(author)
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Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection
- 2023
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In: Biomedicine & Pharmacotherapy. - 0753-3322. ; 168
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Journal article (peer-reviewed)abstract
- Given the rise of multidrug-resistant (MDR) Pseudomonas aeruginosa infections, alternative treatments are needed. Anti-pseudomonal phage therapy shows promise, but its clinical application is limited due to the development of resistance and a lack of biofilm penetration. Recently, adjuvants like CaEDTA have shown the ability to enhance the effectiveness of combined antimicrobial agents. Here, we tested a phage-adjuvant com-bination and demonstrated the effectiveness of intranasally inhaled phage (KKP10) + CaEDTA in addition to ceftazidime/avibactam (CZA) for chronic P. aeruginosa lung infections. The results emphasize that intranasal inhalation of phage along with CaEDTA can successfully re-sensitize MDR P. aeruginosa to CZA in a triple combination treatment. This promising approach shows potential as a therapy for chronic respiratory tract infections.
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27. |
- Tiegs, Scott D., et al.
(author)
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Global patterns and drivers of ecosystem functioning in rivers and riparian zones
- 2019
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In: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
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Journal article (peer-reviewed)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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28. |
- Wu, X. N., et al.
(author)
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Increased EZH2 expression in prostate cancer is associated with metastatic recurrence following external beam radiotherapy
- 2019
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In: Prostate. - : Wiley. - 0270-4137. ; 79:10, s. 1079-1089
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Journal article (peer-reviewed)abstract
- Background Enhancer of zeste 2 (EZH2) promotes prostate cancer progression. We hypothesized that increased EZH2 expression is associated with postradiotherapy metastatic disease recurrence, and may promote radioresistance. Methods EZH2 expression was investigated using immunohistochemistry in diagnostic prostate biopsies of 113 prostate cancer patients treated with radiotherapy with curative intent. Associations between EZH2 expression in malignant and benign tissue in prostate biopsy cores and outcomes were investigated using univariate and multivariate Cox regression analyses. LNCaP and PC3 cell radiosensitivity was investigated using colony formation and gamma H2AX assays following UNC1999 chemical probe-mediated EZH2 inhibition. Results While there was no significant association between EZH2 expression and biochemical recurrence following radiotherapy, univariate analysis revealed that prostate cancer cytoplasmic and total EZH2 expression were significantly associated with metastasis development postradiotherapy (P = 0.034 and P = 0.003, respectively). On multivariate analysis, the prostate cancer total EZH2 expression score remained statistically significant (P = 0.003), while cytoplasmic EZH2 expression did not reach statistical significance (P = 0.053). No association was observed between normal adjacent prostate EZH2 expression and biochemical recurrence or metastasis. LNCaP and PC3 cell treatment with UNC1999 reduced histone H3 lysine 27 tri-methylation levels. Irradiation of LNCaP or PC3 cells with a single 2 Gy fraction with UNC1999-mediated EZH2 inhibition resulted in a statistically significant, though modest, reduction in cell colony number for both cell lines. Increased gamma H2AX foci were observed 24 hours after ionizing irradiation in LNCaP cells, but not in PC3, following UNC1999-mediated EZH2 inhibition vs controls. Conclusions Taken together, these results reveal that high pretreatment EZH2 expression in prostate cancer in diagnostic biopsies is associated with an increased risk of postradiotherapy metastatic disease recurrence, but EZH2 function may only at most play a modest role in promoting prostate cancer cell radioresistance.
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31. |
- Biel, D., et al.
(author)
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Combining tau-PET and fMRI meta-analyses for patient-centered prediction of cognitive decline in Alzheimer's disease
- 2022
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In: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Journal article (peer-reviewed)abstract
- Background Tau-PET is a prognostic marker for cognitive decline in Alzheimer's disease, and the heterogeneity of tau-PET patterns matches cognitive symptom heterogeneity. Thus, tau-PET may allow precision-medicine prediction of individual tau-related cognitive trajectories, which can be important for determining patient-specific cognitive endpoints in clinical trials. Here, we aimed to examine whether tau-PET in cognitive-domain-specific brain regions, identified via fMRI meta-analyses, allows the prediction of domain-specific cognitive decline. Further, we aimed to determine whether tau-PET-informed personalized cognitive composites capture patient-specific cognitive trajectories more sensitively than conventional cognitive measures. Methods We included Alzheimer's Disease Neuroimaging Initiative (ADNI) participants classified as controls (i.e., amyloid-negative, cognitively normal, n = 121) or Alzheimer's disease-spectrum (i.e., amyloid-positive, cognitively normal to dementia, n = 140), plus 111 AVID-1451-A05 participants for independent validation (controls/Alzheimer's disease-spectrum=46/65). All participants underwent baseline F-18-flortaucipir tau-PET, amyloid-PET, and longitudinal cognitive testing to assess annual cognitive changes (i.e., episodic memory, language, executive functioning, visuospatial). Cognitive changes were calculated using linear mixed models. Independent meta-analytical task-fMRI activation maps for each included cognitive domain were obtained from the Neurosynth database and applied to tau-PET to determine tau-PET signal in cognitive-domain-specific brain regions. In bootstrapped linear regression, we assessed the strength of the relationship (i.e., partial R-2) between cognitive-domain-specific tau-PET vs. global or temporal-lobe tau-PET and cognitive changes. Further, we used tau-PET-based prediction of domain-specific decline to compose personalized cognitive composites that were tailored to capture patient-specific cognitive decline. Results In both amyloid-positive cohorts (ADNI [age = 75.99 +/- 7.69] and A05 [age = 74.03 +/- 9.03]), cognitive-domain-specific tau-PET outperformed global and temporal-lobe tau-PET for predicting future cognitive decline in episodic memory, language, executive functioning, and visuospatial abilities. Further, a tau-PET-informed personalized cognitive composite across cognitive domains enhanced the sensitivity to assess cognitive decline in amyloid-positive subjects, yielding lower sample sizes required for detecting simulated intervention effects compared to conventional cognitive endpoints (i.e., memory composite, global cognitive composite). However, the latter effect was less strong in A05 compared to the ADNI cohort. Conclusion Combining tau-PET with task-fMRI-derived maps of major cognitive domains facilitates the prediction of domain-specific cognitive decline. This approach may help to increase the sensitivity to detect Alzheimer's disease-related cognitive decline and to determine personalized cognitive endpoints in clinical trials.
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33. |
- Casares, L., et al.
(author)
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The synthetic triterpenoids CDDO-TFEA and CDDO-Me, but not CDDO, promote nuclear exclusion of BACH1 impairing its activity
- 2022
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In: Redox Biology. - : Elsevier BV. - 2213-2317. ; 51
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Journal article (peer-reviewed)abstract
- The transcription factor BACH1 is a potential therapeutic target for a variety of chronic conditions linked to oxidative stress and inflammation, as well as cancer metastasis. However, only a few BACH1 degraders/inhibitors have been described. BACH1 is a transcriptional repressor of heme oxygenase 1 (HMOX1), which is positively regulated by transcription factor NRF2 and is highly inducible by derivatives of the synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO). Most of the therapeutic activities of these compounds are due to their anti-inflammatory and antioxidant properties, which are widely attributed to their ability to activate NRF2. However, with such a broad range of action, these compounds have other molecular targets that have not been fully identified and could also be of importance for their therapeutic profile. Herein we identified BACH1 as a target of two CDDO-derivatives (CDDO-Me and CDDO-TFEA), but not of CDDO. While both CDDO and CDDO-derivatives activate NRF2 similarly, only CDDO-Me and CDDO-TFEA inhibit BACH1, which explains the much higher potency of these CDDO-derivatives as HMOX1 inducers compared with unmodified CDDO. Notably, we demonstrate that CDDO-Me and CDDO-TFEA inhibit BACH1 via a novel mechanism that reduces BACH1 nuclear levels while accumulating its cytoplasmic form. In an in vitro model, both CDDO-derivatives impaired lung cancer cell invasion in a BACH1-dependent and NRF2-independent manner, while CDDO was inactive. Altogether, our study identifies CDDO-Me and CDDO-TFEA as dual KEAP1/BACH1 inhibitors, providing a rationale for further therapeutic uses of these drugs.
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34. |
- Costello, David M., et al.
(author)
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Global patterns and controls of nutrient immobilization on decomposing cellulose in riverine ecosystems
- 2022
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In: Global Biogeochemical Cycles. - : John Wiley & Sons. - 0886-6236 .- 1944-9224. ; 36:3
-
Journal article (peer-reviewed)abstract
- Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature. Collectively, we demonstrated that exogenous nutrient supply and immobilization are critical control points for decomposition of organic matter.
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35. |
- Gillespie, S. A., et al.
(author)
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Identification of a 6.6 μ s isomeric state in Ir 175
- 2019
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In: Physical Review C. - 2469-9985. ; 99:6
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Journal article (peer-reviewed)abstract
- An experiment has been performed to study excited states in the neutron-deficient nucleus Ir175 via the use of the JUROGAM II high-purity germanium detector array and the RITU gas-filled separator at JYFL, Jyväskylä. By using isomer tagging, an isomeric state with a half-life of 6.58(15) μs has been observed in Ir175 for the first time. It has been established that the isomer decays via a 45.2 (E1)-26.1 (M1) keV cascade to new states below the previously reported ground state in Ir175 with Iπ=(5/2-). We now reassign this (5/2-) state to the isomeric state discovered in this study.
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37. |
- Grill, G., et al.
(author)
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Mapping the world's free-flowing rivers
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 569:7755, s. 215-221
-
Journal article (peer-reviewed)abstract
- Free-flowing rivers (FFRs) support diverse, complex and dynamic ecosystems globally, providing important societal and economic services. Infrastructure development threatens the ecosystem processes, biodiversity and services that these rivers support. Here we assess the connectivity status of 12 million kilometres of rivers globally and identify those that remain free-flowing in their entire length. Only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length and 23 per cent flow uninterrupted to the ocean. Very long FFRs are largely restricted to remote regions of the Arctic and of the Amazon and Congo basins. In densely populated areas only few very long rivers remain free-flowing, such as the Irrawaddy and Salween. Dams and reservoirs and their up- and downstream propagation of fragmentation and flow regulation are the leading contributors to the loss of river connectivity. By applying a new method to quantify riverine connectivity and map FFRs, we provide a foundation for concerted global and national strategies to maintain or restore them.
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40. |
- Hampton, Stephanie E., et al.
(author)
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Ecology under lake ice
- 2017
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In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 20:1, s. 98-111
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Research review (peer-reviewed)abstract
- Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer ‘growing seasons’. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.
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41. |
- Harwit, M., et al.
(author)
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Polarisation observations of VY Canis Majoris H2O 5(32)-4(41) 620.701 GHz maser emission with HIFI
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L51-
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Journal article (peer-reviewed)abstract
- Context. Water vapour maser emission from evolved oxygen-rich stars remains poorly understood. Additional observations, including polarisation studies and simultaneous observation of different maser transitions may ultimately lead to greater insight. Aims. We have aimed to elucidate the nature and structure of the VY CMa water vapour masers in part by observationally testing a theoretical prediction of the relative strengths of the 620.701 GHz and the 22.235 GHz maser components of ortho H2O. Methods. In its high-resolution mode (HRS) the Herschel Heterodyne Instrument for the Far Infrared (HIFI) offers a frequency resolution of 0.125 MHz, corresponding to a line-of-sight velocity of 0.06 km s(-1), which we employed to obtain the strength and linear polarisation of maser spikes in the spectrum of VY CMa at 620.701 GHz. Simultaneous ground based observations of the 22.235 GHz maser with the Max-Planck-Institut fur Radioastronomie 100-m telescope at Effelsberg, provided a ratio of 620.701 GHz to 22.235 GHz emission. Results. We report the first astronomical detection to date of H2O maser emission at 620.701 GHz. In VY CMa both the 620.701 and the 22.235 GHz polarisation are weak. At 620.701 GHz the maser peaks are superposed on what appears to be a broad emission component, jointly ejected from the star. We observed the 620.701 GHz emission at two epochs 21 days apart, both to measure the potential direction of linearly polarised maser components and to obtain a measure of the longevity of these components. Although we do not detect significant polarisation levels in the core of the line, they rise up to approximately 6% in its wings.
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42. |
- Leshan, D., et al.
(author)
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Ca-EDTA restores the activity of ceftazidime- avibactam or aztreonam against carbapenemase- producing Klebsiella pneumoniae infections
- 2023
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In: iScience. - 2589-0042. ; 26:7
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Journal article (peer-reviewed)abstract
- Developing an effective therapy to overcome carbapenemase-positive Klebsiella pneumoniae (CPKp) is an important therapeutic challenge that must be ad-dressed urgently. Here, we explored a Ca-EDTA combination with aztreonam or ceftazidime-avibactam in vitro and in vivo against diverse CPKp clinical iso-lates. The synergy testing of this study demonstrated that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combination was significantly effective in eliminating planktonic and mature biofilms in vitro, as well as eradicating CPKp infections in vivo. Both combinations revealed significant therapeutic efficacies in reducing bacterial load in internal organs and protecting treated mice from mor-tality. Conclusively, this is the first in vitro and in vivo study to demonstrate that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combinations pro-vide favorable efficacy and safety for successful eradication of carbapenemase-producing Klebsiella pneumoniae planktonic and biofilm infections.
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43. |
- O'Malley, D., et al.
(author)
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Prevalence of and risk factors associated with sexual health issues in primiparous women at 6 and 12 months postpartum; a longitudinal prospective cohort study (the MAMMI study)
- 2018
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In: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 18:196
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Journal article (peer-reviewed)abstract
- Background: Many women are not prepared for changes to their sexual health after childbirth. The aim of this paper is to report on the prevalence of and the potential risk factors (pre-pregnancy dyspareunia, mode of birth, perineal trauma and breastfeeding) for sexual health issues (dyspareunia, lack of vaginal lubrication and a loss of interest in sexual activity) at 6 and 12 months postpartum. Methods: A longitudinal cohort study of 832 first-time mothers who were recruited in early pregnancy and returned postnatal surveys at 3, 6, 9 and 12 months postpartum were assessed for sexual health issues and associated risk factors. Results: Nearly half of the women (46.3%) reported a lack of interest in sexual activity, 43% experienced a lack of vaginal lubrication and 37.5% of included women had dyspareunia 6 months after birth. On univariate analysis, vacuum-assisted birth, 2nd degree perineal tears, 3rd degree perineal tears and episiotomy were all associated with dyspareunia 6 months postpartum, but, of these only 3rd degree tears, in association with breastfeeding and pre-existing dyspareunia, remained significant on multivariable analysis. Breastfeeding, in combination, with other significant factors, was associated with dyspareunia, a lack of vaginal lubrication and a loss of interest in sexual activity 6 months postpartum, and, dissatisfaction with body image emerged as a significant factor associated with lack of interest in sexual activity at 12 months postpartum. Pre-pregnancy dyspareunia and breastfeeding emerged as common factors associated with all three outcomes of dyspareunia, a lack of vaginal lubrication and a loss of interest in sexual activity at 6 months postpartum. Conclusion: Breastfeeding and pre-existing dyspareunia are associated with sexual health issues at 6 months postpartum. Pre-existing dyspareunia is associated with a lack of vaginal lubrication at 12 months postpartum and breastfeeding is associated with dissatisfaction with body image. Preparing women and their partners during the antenatal period and advising on simple measures, such as use of lubrication to avoid or minimise sexual health issues, could potentially remove stress, anxiety and fears regarding intimacy after birth. Introducing the topic of pre-existing sexual health issues antenatally may facilitate appropriate support, treatment or counselling for women.
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- Shein, A. M. S., et al.
(author)
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High prevalence of mgrB-mediated colistin resistance among carbapenem-resistant Klebsiella pneumoniae is associated with biofilm formation, and can be overcome by colistin-EDTA combination therapy
- 2022
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Journal article (peer-reviewed)abstract
- The global prevalence of colistin-resistant Klebsiella pneumoniae (ColRkp) facilitated by chromosomal and plasmid-mediated Ara4N or PEtN-remodeled LPS alterations has steadily increased with increased colistin usage for treating carbapenem-resistant K. pneumoniae (CRkp). Our study demonstrated the rising trend of ColRkp showing extensively and pandrug-resistant characteristics among CRkp, with a prevalence of 28.5%, which was mediated by chromosomal mgrB, pmrB, or phoQ mutations (91.5%), and plasmid-mediated mcr-1.1, mcr-8.1, mcr-8.2 alone or in conjunction with R256G PmrB (8.5%). Several genetic alterations in mgrB (85.1%) with increased expressions of Ara4N-related phoPQ and pmrK were critical for establishing colistin resistance in our isolates. In this study, we discovered the significant associations between extensively drug-resistant bacteria (XDR) and pandrug-resistant bacteria (PDR) ColRkp in terms of moderate, weak or no biofilm-producing abilities, and altered expressions of virulence factors. These ColRkp would therefore be very challenging to treat, emphasizing for innovative therapy to combat these infections. Regardless of the underlying colistin-resistant mechanisms, colistin-EDTA combination therapy in this study produced potent synergistic effects in both in vitro and in vivo murine bacteremia, with no ColRkp regrowth and improved animal survival, implying the significance of colistin-EDTA combination therapy as systemic therapy for unlocking colistin resistance in ColRkp-associated bacteremia.
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- Baker, Jessica H., et al.
(author)
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Body Dissatisfaction in Adolescent Boys
- 2019
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In: Developmental Psychology. - : American Psychological Association (APA). - 0012-1649 .- 1939-0599. ; 55:7, s. 1566-1578
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Journal article (peer-reviewed)abstract
- Body dissatisfaction is a significant mental health symptom present in adolescent girls and boys. However, it is often either disregarded in adolescent boys or examined using assessments that may not resonate with males. The present study addresses these issues, examining the manifestation, etiology, and correlates of 3 facets of body dissatisfaction in adolescent boys. Adolescent male twins aged 16- to 17-years-old from the Swedish Twin Study of Child and Adolescent Development were included along with a female comparison group: 915 monozygotic and 671 dizygotic same-sex twins. Body dissatisfaction was defined using measures of height dissatisfaction, muscle dissatisfaction, and the body dissatisfaction subscale of the Eating Disorder Inventory (EDI-BD). We examined the prevalence of body dissatisfaction, whether the facets of body dissatisfaction were phenotypically and etiologically distinct, and associations with specific externalizing and internalizing symptoms. For boys, muscle dissatisfaction scores were greater than height dissatisfaction scores. Results also indicated that height and muscle dissatisfaction were phenotypically and etiologically distinct from the EDI-BD. Unique associations were observed with externalizing and internalizing symptoms: muscle dissatisfaction with symptoms of bulimia nervosa and the EDI-BD with internalizing symptoms, body mass index, and drive for thinness. The facets of body dissatisfaction were also largely distinct in girls and unique between-sex associations with externalizing and internalizing symptoms emerged. Overall, male-oriented aspects of body dissatisfaction are distinct from female-oriented aspects of body dissatisfaction. To capture the full picture of male body dissatisfaction, multiple facets must be addressed.
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