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The removal preference of Fe(III), Fe(II), and in situ Fe(III) in coagulation when treating NOM and TC
No full textTetracyclines (TCs) are a representative class of emerging organic pollutants. Their presence may affect the coagulation process commonly used in water treatment units. Fe salts are widely employed as coagulants in the coagulation process. However, there are few systematic studies of Fe(III), Fe(II), and in situ Fe(III) (oxide-assisted Fe(II) coagulation) for the treatment of natural organics (NOMs) in the presence or absence of tetracycline (TC). In this study, the coagulation process and performance of Fe(III), Fe(II) and in-situ Fe(III) generated by the oxide of potassium persulfate (PS) for the removal of humic acid (HA), NOM, NOM with TC were systematically studied. The flocculation index showed that the presence of TC lagged the floc growth. It was due to the reaction of TC with Fe, hindering the hydrolysis, aggregation and precipitation of Fe to form flocs. The removal performance evaluated by the EEM, SEC and LC-MS suggested the removal preference of Fe(III) and Fe(II) was NOM and TC, respectively. And the in-situ Fe(III) was superior than Fe(III) and Fe(II) in removing NOM and TC. It was attributed to the free radical oxidation by PS and the coagulation through in-situ Fe(III). The concentration of PS determined which of them was the main reason responsible for the enhanced organics removal. The PS at the concentration of 0.02 mM was the key point. The oxidation of organics by the free radicals dominated the enhance removal of organics when PS concentration was lower than 0.02 mM. Otherwise, it was the coagulation of the in-situ Fe(III) responsible for the enhanced removal of organics. The results of floc characterization by TEM, SEM and FTIR further indicated that the in-situ Fe(III) retained higher proportion organics with the increased concentration of PS. This study provides information on which Fe salt coagulant to choose for the treatment of TC-contaminated water and the insights of the interactions fate of Fe flocs with NOM and TC from the perspective of coagulation in natural environments
Enhancing the production of chlorophyll f in the cyanobacterium Synechocystis sp. PCC 6803
No full textOne potential approach to improve the productivity of cyanobacteria and microalgae is to enhance photosynthetic efficiency by introducing far-red absorbing pigment molecules (such as chlorophylls f and d) into the photosynthetic apparatus to expand the range of photosynthetically active radiation. We have shown previously that expressing the ChlF subunit of Chroococcidiopsis thermalis PCC 7203 in the model cyanobacterium Synechocystis sp. PCC 6803 (Syn6803) is sufficient to drive the production of chlorophyll f (Chl f), but only to low levels (0.24% Chl f/Chl a). By using the strong Pcpc560 promoter and an N-terminal truncated derivative of ChlF, we have been able to increase the yield of Chl f in white light by over 30-fold to about 8.2% Chl f/Chl a, close to the level displayed by far-red photoacclimated C. thermalis 7203. Additionally, we demonstrate that ChlF from Fisherella thermalis PCC 7521, like ChlF from C. thermalis 7203, assembles into a variant of the monomeric photosystem II (PSII) core complex termed the super-rogue PSII complex when expressed in Syn6803. This contrasts with the originally reported formation of a ChlF homodimeric complex in Synechococcus sp. PCC 7002. Overall, our work is an important starting point for mechanistic and structural studies of super-rogue PSII and for incorporating Chl f into the photosynthetic apparatus of Syn6803
Body mass index and risk of Hodgkin's lymphoma: insights from a Norwegian cohort study
No full textBackground
Several studies have reported positive associations between higher body mass index (BMI) and risk of Hodgkin's lymphoma. However, the evidence is not entirely consistent. We investigated the association between BMI and Hodgkin's lymphoma in a large Norwegian cohort with up to 50 years follow-up.
Methods
The analytical dataset included 1,723,692 men and women aged 16-75 years at baseline in 1963-1975. Multivariable Cox regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between BMI and Hodgkin's lymphoma incidence.
Results
During 56.1 million person-years of follow-up, 1608 incident Hodgkin's lymphoma cases occurred. Compared to individuals with BMI 18.5-<25, the HRs (95% CIs) for those with a BMI of 15-<18.5, 25-<30, and ≥30 were 0.87 (0.59-1.27), 1.05 (0.94-1.18), and 1.61 (1.35-1.91), respectively, and 1.57 (1.30-1.90) and 1.80 (1.24-2.62) for obesity grade 1 and grade 2, respectively. A positive association was also observed per 5 kg/m2 increment with a HR (95% CI) of 1.16 (1.08-1.24) overall, 1.20 (1.09-1.31) in women, and 1.08 (0.96-1.20) in men. Positive associations were also observed between obesity vs. normal weight in early adulthood (age 16-29 years) and Hodgkin's lymphoma (HR, 95% CIs: 1.89, 1.10-3.22, ptrend<0.0001, n=489 cases) and between obesity and early-onset (age <50 years at diagnosis) disease (HR, 95% CIs: 1.67, 1.01-2.78, ptrend<0.0001, n=393 cases).
Conclusion
The positive associations observed between higher BMI overall and in young adulthood and Hodgkin's lymphoma and between BMI and early-onset disease emphasize the potential role of adiposity in development of this malignancy
Life cycle impacts of structural deterioration and seismic events on cross-laminated timber buildings
No full textLife cycle assessment (LCA) has become the preferred tool for evaluating the environmental impacts of buildings over their lifetime and informing infrastructure-related policy decisions. Traditionally, LCA is conducted using static inputs, which assume a building’s current performance remains representative of its long-term carbon emissions. However, buildings naturally deteriorate over time—a factor particularly significant for timber structures—and this deterioration can be exacerbated by extreme natural hazards such as earthquakes. The associated repair or replacement activities introduce additional material and energy demands that influence environmental performance. This study introduces a stochastic approach to incorporate the environmental impacts associated with repair and replacement of timber buildings subjected to seismic hazards. The approach is comprehensive in nature, it accounts for the progressive structural deterioration of timber over time, demonstrating its substantial influence on structural performance and subsequent LCA results. The proposed framework is applied to a series of multi-storey cross-laminated timber (CLT) apartment buildings located in a seismically active region in Europe. Using nonlinear response history analyses (NRHAs) under multiple earthquake intensities, various structural deterioration rates are considered to assess their effects on building performance. A comparative LCA is conducted to analyse the contributions from both structural and non-structural damage, while also evaluating the impacts of design behaviour factors and number of storeys. Our findings highlight the importance of an integrated approach to incorporate long-term structural deterioration and seismic hazard impacts into LCA, providing a more realistic and dynamic assessment of timber buildings’ environmental footprint over their lifecycle
Direct oral anticoagulants versus no anticoagulation for the prevention of stroke in survivors of intracerebral haemorrhage with atrial fibrillation (PRESTIGE-AF): a multicentre, open-label, randomised, phase 3 trial
No full textBackground
Direct oral anticoagulants (DOACs) reduce the rate of thromboembolism in patients with atrial fibrillation but the benefits and risks in survivors of intracerebral haemorrhage are uncertain. We aimed to determine whether DOACs reduce the risk of ischaemic stroke without substantially increasing the risk of recurrent intracerebral haemorrhage.
Methods
PRESTIGE-AF is a multicentre, open-label, randomised, phase 3 trial conducted at 75 hospitals in six European countries. Eligible patients were aged 18 years or older with spontaneous intracerebral haemorrhage, atrial fibrillation, an indication for anticoagulation, and a score of 4 or less on the modified Rankin Scale. Patients were randomly assigned (1:1) to a DOAC or no anticoagulation, stratified by intracerebral haemorrhage location and sex. Only the events adjudication committee was masked to treatment allocation. The coprimary endpoints were first ischaemic stroke and first recurrent intracerebral haemorrhage. Hierarchical testing for superiority and non-inferiority, respectively, was performed in the intention-to-treat population. The margin to establish non-inferiority regarding intracerebral haemorrhage was less than 1·735. The safety analysis was done in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT03996772, and is complete.
Findings
Between May 31, 2019, and Nov 30, 2023, 319 participants were enrolled and 158 were randomly assigned to the DOAC group and 161 to the no anticoagulant group. Patients' median age was 79 years (IQR 73–83). 113 (35%) of 319 patients were female and 206 (65%) were male. Median follow-up was 1·4 years (IQR 0·7–2·3). First ischaemic stroke occurred less frequently in the DOAC group than in the no anticoagulant group (hazard ratio [HR] 0·05 [95% CI 0·01–0·36]; log-rank p<0·0001). The rate of all ischaemic stroke events was 0·83 (95% CI 0·14–2·57) per 100 patient-years in the DOAC group versus 8·60 (5·43–12·80) per 100 patient-years in the no anticoagulant group. For first recurrent intracerebral haemorrhage, the DOAC group did not meet the prespecified HR for the non-inferiority margin of less than 1·735 (HR 10·89 [90% CI 1·95–60·72]; p=0·96). The event rate of all intracerebral haemorrhage was 5·00 (95% CI 2·68–8·39) per 100 patient-years in the DOAC group versus 0·82 (0·14–2·53) per 100 patient years in the no anticoagulant group. Serious adverse events occurred in 70 (44%) of 158 patients in the DOAC group and 89 (55%) of 161 patients in the no anticoagulant group. 16 (10%) patients in the DOAC group and 21 (13%) patients in the no anticoagulant group died.
Interpretation
DOACs effectively prevent ischaemic strokes in survivors of intracerebral haemorrhage with atrial fibrillation but a part of this benefit is offset by a substantially increased risk of recurrent intracerebral haemorrhage. To optimise stroke prevention in these vulnerable patients, further evidence from ongoing trials and a meta-analysis of randomised data is needed, as well as the evaluation of safer medical or mechanical alternatives for selected patients.
Funding
European Commission
Single-plume and multi-plume atomisation of ethanol with different levels of water content at hot fuel conditions
No full textProducing anhydrous ethanol involves separation of ethanol and water in an energy intensive process. It is possible to use ethanol (without any gasoline) as a fuel in countries where the ambient temperature is high enough that the low vapour pressure of pure ethanol does not give rise to significant cold weather driveability issues. From a cost and carbon footprint perspective, it is highly desirable to use hydrous ethanol, but there is a clear need to understand the effect of water content in ethanol on the spray formation process and hence mixture formation. The present paper presents results from an optical experimental investigation into the effects of 0–15 % water content per volume in ethanol on spray formation, using high-speed imaging and droplet sizing. Experiments were carried out with fuel temperatures in the range 20–110 °C at 1.0 bar and 0.5 bar gas pressure. Iso-octane and water were also tested for comparison. Multi-hole and isolated single-hole injections were studied to decouple effects from plume-to-plume interactions. Single-plume hydrous ethanol fuels showed initial delay out of the nozzle with shorter penetration but gradually achieved or surpassed the liquid penetration of the anhydrous fuel. Increased water content was generally associated with reduced single plume cone angle between 20 and 90 °C, but at 110 °C the order was reversed, with the hydrous ethanol blends having greater cone angle than the anhydrous which has implications for spray collapse upon multi-plume operation. At 20 °C, 1.0 bar, anhydrous ethanol showed larger droplets than iso-octane by ∼5 %, with the addition of 10 % water increasing the SMD by about a further 5 %. Water showed larger SMD than the fuels by 30–40 %. At 110 °C, 0.5 bar, all fuels showed smaller droplets by 20–30 % than at the subcooled condition. When comparing the isolated single-plume spray with the respective plume pair of the multi-hole experiment for anhydrous ethanol and iso-octane at subcooled conditions, it was observed that the plume pair had higher penetration. This could be attributed to near-nozzle effects from interacting adjacent plumes, differences in gas entrainment and drag. At superheated conditions, the penetration of the multi-hole plume pair for iso-octane was similar to that of the isolated single-hole plume spray. However, for ethanol it was clearly shorter due to presence of plume merging and initiation of spray collapse, effects that were absent for the single-plume configuration. The fact that increasing water content was associated with wider near-nozzle plume angle at superheated conditions and stronger propensity for plume merging and spray collapse, despite the slightly lower vapour pressure, suggests that other effects, e.g. related to the higher heat capacity of water and potential temperature saturation upon phase change, could dominate the process
A generalised framework for phase field-based modelling of coupled problems: application to thermo-mechanical fracture, hydraulic fracture, hydrogen embrittlement and corrosion
No full textWe present a novel, generalised formulation to treat coupled structural integrity problems by combining phase field and multi-physics modelling. The approach exploits the versatility of the heat transfer equation and is therefore well suited to be adopted in commercial finite element packages, requiring only integration point-level implementation. This aspect is demonstrated here by implementing coupled, multi-variable phenomena through simple UMAT and UMATHT subroutines in the finite element package Abaqus. The generalised theoretical and computational framework presented is particularised to four problems of engineering and scientific relevance: thermo-mechanical fracture, hydraulic fracture, hydrogen-assisted cracking and metallic corrosion. 2D and 3D problems are considered. The results reveal a very good agreement with experimental data, and existing numerical and analytical solutions. The user subroutines developed are made freely available at https://mechmat.web.ox.ac.uk/code
Metabolic profiling of cancer cells and its implications for targeted metabolic therapies
No full textMetabolic reprogramming is a hallmark of cancer and is partially regulated by the PI3K/Akt pathway. Epithelial ovarian cancer (EOC) is one of the most common gynaecological cancers and dysregulated PI3K/Akt signalling is frequently detected. However, the metabolic impact remains unclear. Here, using the ID8 in vitro and in vivo model of EOC, I found that the deletion of Pten (i.e., the negative regulator of Akt) enhanced glycolysis, and modulated NAD+ metabolism and arginine synthesis.
The enhanced glycolysis induced by the hyperactive PI3K/Akt and Ras signalling may create a metabolic bottleneck by increasing the demand for NAD+ (a key glycolytic co-factor). Indeed, we previously showed NAD+ depletion by FK866, which inhibits NAD+ salvage synthesis, sensitized EOC cells to the PARP inhibitor Olaparib. Using a panel of EOC cells, I confirmed the higher sensitivity of the combination treatment in Ras/PI3K mutant cells. Mechanistically, higher DNA damage and oxidative stress were observed. The combination treatment improved median survival in the ID8 mouse model.
Lactate has been reported to fuel the TCA cycle in cancer cells. More recently, lactate acidosis uncouples glycolysis from the TCA cycle, which the lactate metabolon model can rationalize. Exogenous lactate forms a kinetically resolved pool from that derived from glycolysis and its derived pyruvate enters mitochondria before mixing with the glycolysis-derived pool. To test this hypothesis, I traced the relative contribution of glucose and exogenous lactate to citrate. A higher correlation was observed between labelling in citrate and pyruvate compared to exogenous lactate, which is inconsistent with the lactate metabolon model. Examining the roles of MCT1 and MCT4 (main lactate transporters) in this phenomenon I found that MCT1 was the major lactate transporter, and they were functionally redundant, which implies dual targeting may be necessary for therapeutic benefits.Open Acces
Data-driven Modelling for Guided Wave Structural Health Monitoring and Prognostic Health Management on Aeronautical Structures
No full textHealth Monitoring (GWSHM) and Prognostic Health Management (PHM) on aeronautical structures. Main attention is paid to damage detection and localisation on Carbon Fiber Reinforced Polymer (CFRP) panels together with the Remaining Useful Life (RUL) prediction of aircraft turbofans.
A baseline-dependent GWSHM approach on CFRP plates is proposed integrating the statistical autoregressive (AR) modelling and signal compression techniques. An adaptive block-wise down-sampling method is designed to compress guided wave signals and compared to other signal compression techniques, and the compressed measurements are processed by AR models to extract damage-sensitive features. Further validations are implemented on both quasi-isotropic and anisotropic CFRP coupons. Various variables, including the AR model parameters, number of tone burst cycles and signal compression ratios, are investigated regarding their effects on the damage detection and localisation.
Baseline-free GWSHM is investigated within the aeronautical composite cases. Existing baseline-free techniques are reviewed, with several of them experimentally compared considering material anisotropy, temperature variations, multiple damages, boundary reflections and structural complexities, e.g., stiffeners.
Furthermore, a novel data-driven baseline-free technique is presented based on unsupervised shapelets and shift-invariant dictionary learning. The proposed method can detect and localise potential damages in complex composite structures, e.g., stiffened panels, when integrated with the building block philosophy. The effectiveness and robustness of the proposed method is validated through experimental investigations and compared with several existing baseline-free techniques for damage detection and localisation under varying temperatures.
During the transition from GWSHM to PHM, the RUL prediction of aircraft engines is implemented by a proposed hybrid data-driven approach which is able to model degradation behaviour of turbofans under varying environmental and operational conditions (EOCs) while yielding satisfactory RUL estimates simultaneously.Open Acces
Efficacy and safety of epicutaneous immunotherapy in peanut-allergic toddlers: open-label extension to EPITOPE
No full textBackground
The pivotal phase 3 EPITOPE trial, a 12-month, double-blind, placebo-controlled study of epicutaneous immunotherapy with the VIASKIN patch containing 250 μg of peanut protein (VP250), previously reported significant treatment response versus placebo in peanut-allergic toddlers aged 1 through 3 years.
Objective
To assess the interim efficacy and safety of VP250 from the first year of the EPITOPE open-label extension (OLE) study.
Methods
Eligible participants enrolled in the OLE study for up to 3 years of total treatment with annual double-blind, placebo-controlled food challenges (DBPCFCs) and safety assessments; here we report the first-year OLE (year 2) results.
Results
A total of 266 EPITOPE participants enrolled in the OLE study; 244 underwent month 24 DBPCFC (n = 166 VP250; n = 78 placebo). After 24 months of VP250, 81.3% reached an eliciting dose (ED) ≥1000 mg, 63.8% reached an ED ≥2000 mg, and 55.9% completed the DBPCFC (cumulative dose: 3444 mg) without meeting stopping criteria. No treatment-related anaphylaxis or serious treatment-related adverse events occurred during year 2 in this treatment arm. Local application-site reactions occurred less frequently in year 2 versus year 1. In placebo-treated EPITOPE participants, outcomes after 1 year of open-label VP250 were consistent with EPITOPE treatment results: 62.7% reached an ED ≥1000 mg, 36.5% reached an ED ≥2000 mg, and 28.4% completed the DBPCFC without meeting stopping criteria; and there was 1 treatment-related anaphylaxis event.
Conclusions
Two years of VP250 in young peanut-allergic children demonstrated continued increases in treatment effect without new safety signals. This supports the potential of VP250 as a safe and effective treatment for peanut allergy in young children.
Clinicaltrials.gov
NCT03859700