All-atom molecular dynamics simulations showing the dynamics of small organic molecules in water-solvated polyelectrolyte brush layers.

Polyelectrolyte brushes can introduce functionality to surfaces and because of this, these brushes have been studied extensively. In many applications, these brushes are used in solutions that contain a variety of molecules. While the interaction between polyelectrolyte brushes and molecules has been studied via coarse-grained simulations and experiments, such interaction has not been studied in molecular detail. An understanding of interactions in such molecular detail may prove crucial in the design of future brush coatings that can enable desired adsorption of different organic and biological molecules. Therefore, we present a first all-atom molecular dynamics simulations study of poly(sodium acrylate) brushes in contact with a small organic molecule, γ-butyrolactone. Within this molecular framework, we study the interaction of this lactone molecule with the brush layer and study the ensuing absorption and dynamics of the lactone inside the brush layer. The lactone is found to prefer to remain in the bulk solution; however, when absorbed, lactone molecules are found to have significantly reduced mobilities as compared to that in the bulk solution and are able to massively influence the properties of the brush-entrapped water molecules. These findings provide unprecedented details about the absorption-driven changes to molecular structure and dynamics of the lactone molecules and the water molecules inside the brush layer and can only be uncovered by our all-atom MD simulations. Such explicit and atomistically-resolved information, taking into account the specific chemical nature of the interacting systems, is rare in the context of designing polymer and PE brush-based coatings. Thus, we anticipate that our findings will be crucial in the design of future brush coatings aimed at providing adsorption platforms for different organic and biomolecules.

Predictors of survival in autoimmune liver disease overlap syndromes.

BACKGROUND: Survival in patients with autoimmune liver disease overlap syndromes (AILDOS) compared to those with single autoimmune liver disease is unclear. AIM: To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death. METHODS: Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap (AIH-PBC) or autoimmune hepatitis and primary sclerosing cholangitis overlap (AIH-PSC) and were identified from three tertiary centres for this cohort study. Liver-related death or transplantation (liver-related mortality) was determined using a population-based data linkage system. Prognostic scores for liver-related death were compared for accuracy [including liver outcome score (LOS), Hepascore, Mayo Score, model for end-stage liver disease (MELD) score and MELD incorporated with serum sodium (MELD-Na) score]. RESULTS: Twenty-two AILDOS patients were followed for a median of 3.1 years (range, 0.35-7.7). Fourteen were female, the median age was 46.7 years (range, 17.8 to 82.1) and median Hepascore was 1 (range, 0.07-1). At five years post enrolment, 57% of patients remained free from liver-related mortality (74% AIH-PBC, 27% AIH-PSC). There was no significant difference in survival between AIH-PBC and AIH-PSC. LOS was a significant predictor of liver-related mortality (P < 0.05) in patients with AIH-PBC (n = 14) but not AIH-PSC (n = 8). A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients (P = 0.012, log-rank test, 100% sensitivity, 77.8% specificity) (Harrell's C-statistic 0.867). The MELD score, MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group. CONCLUSION: Survival in the rare, AILDOS is unclear. The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients. Further trials investigating predictors of survival in AILDOS are required.

Combined additive effects of neuronal membrane glycoprotein GPM6a and the intercellular cell adhesion molecule ICAM5 on neuronal morphogenesis.

The mechanisms underlying neuronal development and synaptic formation in the brain depend on intricate cellular and molecular processes. The neuronal membrane glycoprotein GPM6a promotes neurite elongation, filopodia/spine formation, and synapse development, yet its molecular mechanisms remain unknown. Since the extracellular domains of GPM6a (ECs) command its function, we investigated the interaction between ICAM5, the neuronal member of the intercellular adhesion molecule (ICAM) family, and GPM6a's ECs. Our study aimed to explore the functional relationship between GPM6a and ICAM5 in hippocampal culture neurons and cell lines. Immunostaining of 15 days in vitro (DIV) neurons revealed significant co-localization between endogenous GPM6a clusters and ICAM5 clusters in the dendritic shaft. These results were further corroborated by overexpressing GPM6a and ICAM5 in N2a cells and hippocampal neurons at 5 DIV. Moreover, results from the co-immunoprecipitations and cell aggregation assays prove the cis and trans interaction between both proteins in GPM6a/ICAM5 overexpressing HEK293 cells. Additionally, GPM6a and ICAM5 overexpression additively enhanced neurite length, the number of neurites in N2a cells, and filopodia formation in 5 DIV neurons, indicating their cooperative role. These findings highlight the dynamic association between GPM6a and ICAM5 during neuronal development, offering insights into their contributions to neurite outgrowth, filopodia formation, and cell-cell interactions.

Applying UHPLC-HRAM MS/MS Method to Assess Host Cell Protein Clearance during the Purification Process Development of Therapeutic mAbs.

Host cell proteins (HCPs) are one of the process-related impurities that need to be well characterized and controlled throughout biomanufacturing processes to assure the quality, safety, and efficacy of monoclonal antibodies (mAbs) and other protein-based biopharmaceuticals. Although ELISA remains the gold standard method for quantification of total HCPs, it lacks the specificity and coverage to identify and quantify individual HCPs. As a complementary method to ELISA, the LC-MS/MS method has emerged as a powerful tool to identify and profile individual HCPs during the downstream purification process. In this study, we developed a sensitive, robust, and reproducible analytical flow ultra-high-pressure LC (UHPLC)-high-resolution accurate mass (HRAM) data-dependent MS/MS method for HCP identification and monitoring using an Orbitrap Ascend BioPharma Tribrid mass spectrometer. As a case study, the developed method was applied to an in-house trastuzumab product to assess HCP clearance efficiency of the newly introduced POROS™ Caprylate Mixed-Mode Cation Exchange Chromatography resin (POROS Caprylate mixed-mode resin) by monitoring individual HCP changes between the trastuzumab sample collected from the Protein A pool (purified by Protein A chromatography) and polish pool (purified by Protein A first and then further purified by POROS Caprylate mixed-mode resin). The new method successfully identified the total number of individual HCPs in both samples and quantified the abundance changes in the remaining HCPs in the polish purification sample.

The role of urine sodium in acutely decompensated heart failure.

Background: Diuretic resistance is common and results in poor outcome. Spot urine sodium (UrNa) is suggested as a tool to tailor diuretics and improve efficacy of therapy. We prospectively evaluate the prevalence of diuretic resistance, predictors of low spot-UrNa and the prognostic value of spot-UrNa in an unselected ADHF population. Methods: Patients admitted for ADHF and treated with iv diuretics were included. Spot-UrNa was collected 2 h after administration of an IV diuretic bolus. The main endpoint was a composite of HF re-hospitalizations and all-cause mortality at 90 days follow-up. Results: 143 patients were included in this study (median age 81 [75 - 85] years, 55 % male), of which 50 % were newly diagnosed with HF. Low spot-UrNa was independently associated with worse renal function, low serum sodium, and systolic blood pressure, previous loop diuretic and SGLT2i use and loop diuretic administered dose. Both absolute spot-UrNa (HR 0.87, 95 % CI 0.79 - 0.95, P=0.003 per 10 mmol/L increase) and a urinary sodium ≥ 100 mmol/l (HR=0.51, 95 % CI 0.27 - 0.97, P=0.04) significantly predicted the composite endpoint. This association was no longer significant after correction for confounders. Patients with low spot-UrNa attained longer IV diuretic treatment and a higher cumulative IV diuretic dose. Conclusions: Spot-UrNa is prevalent and occurs more often in patients with more progressed cardio-renal disease. Spot-UrNa significantly predicts 90-day HF hospital-free survival in ADHF. Further studies are needed evaluating the effect of UrNa guided diuretic treatment on clinical endpoints.

Controlled atmosphere as cold chain support for extending postharvest life in cabbage.

Postharvest management of cabbage relies on high-intensity cooling to control postharvest physiology, minimising quality loss despite incurring significant energy and environmental costs. As an alternative, we hypothesised that controlled atmosphere (CA) could allow increased storage temperature by supporting physiological regulation, while maintaining quality and reducing energy demand. This study examined the effect CA (1.5 kPa CO2 and 6 kPa O2) at 5 or 10 °C on cabbage quality, with the aim of proposing a more sustainable and resilient supply chain. CA treatment was effective at reducing head respiration at higher temperature, with CA/10 °C treatment achieving lower respiration rates than Control/5 °C. Improved head colour retention and maintenance of stump quality were observed in cabbage under CA conditions. CA effects were seen also at a regulatory level; CA promoted an average of 25.4% reduction in abscisic acid accumulation potentially as part of a wider hypoxia stress response and was successful in decreasing expression of the senescence-coordinating transcription factor BoORE15. This finding was linked with a lower in downstream expression of pheophytinase and subtilisin protease. These results demonstrated that CA treatment fundamentally modified postharvest physiology in cabbage, which can be exploited to enable storage at warmer temperatures, contributing to supply chains with lower energy demand and its associated environmental benefits.

Biological factors and production challenges drive significant UK fruit and vegetable loss.

BACKGROUND: Food loss and waste estimates are highly inconsistent as a result of methodological and systemic differences. Additionally, the absence of in-depth evidence surrounding the biological drivers of food loss and waste precludes targeted mitigation action. To address this challenge, we undertook a metanalysis utilising a systematic literature review combined with industry stakeholder surveys to examine the incidence of food loss and waste in the UK fruit and vegetable supply chain between primary production and retail. RESULTS: We estimated that 37% of fruit and vegetables, equivalent to 2.4 Mt of produce, is lost between production and sale. In the UK, primary production is the main stage responsible for these losses (58%), and is dominated by four crops (apple, onion, carrot and potato), which contribute 71% of total food loss and waste. Quality and supply/demand mismatch are the core drivers, combined with limited ability to control postharvest quality decline as a result of technical or economic barriers. CONCLUSIONS: Innate biological mechanisms contribute to, and detract from, marketable quality generating food loss risks where these cannot be adequately modified or controlled. Through climate change effects, reduced pesticide availability, changing consumer behaviour and increased pressure to reduce resource/energy inputs during pre- and postharvest handling, food loss and waste risk is likely to increase in the short term unless targeted, coordinated action is taken to actively promote its mitigation. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Endovascular treatment in patients with acute ischemic stroke presenting beyond 6 h after symptom onset: An international multicenter cohort study of the EVA-TRISP collaboration.

INTRODUCTION: After positive findings in clinical trials the time window for endovascular thrombectomy (EVT) for patients with an acute ischemic stroke has been expanded up to 24 h from symptom onset or last seen well (LSW). We aimed to compare EVT patients' characteristics and outcomes in the early versus extended time window and to compare outcomes with the DAWN and DEFUSE 3 trial results. PATIENTS AND METHODS: Consecutive EVT patients from 16 mostly European comprehensive stroke centers from the EVA-TRISP cohort were included. We compared rates of 90-day good functional outcomes (Modified Rankin Scale 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality between patients treated in the early (<6 h after onset or LSW) versus extended (6-24 h after onset or LSW) time windows. RESULTS: We included 9313 patients, of which 6876 were treated in the early and 2437 in the extended time window. National Institutes of Health Stroke Scale (NIHSS) score at presentation was lower in patients treated in the extended time window (median 13 [IQR 7-18] vs 15 [IQR 9-19], p < 0.001). The percentage of patients with good functional outcome was slightly lower in the extended time window (37.4% vs 42.2%, p < 0.001). However, rates of successful recanalization, sICH, and mortality were similar. Good functional outcome rates after EVT were slightly lower for patients in the extended window in the EVA-TRISP cohort as compared to DAWN and DEFUSE 3. DISCUSSION AND CONCLUSION: According to this large multicenter cohort study reflecting daily clinical practice, EVT use in the extended time window appears safe and effective.

Endovascular Thrombectomy Alone for Large Vessel Occlusion: A Cost-Effectiveness Evaluation Based on Meta-Analyses.

BACKGROUND: The benefit of intravenous thrombolysis with alteplase before endovascular thrombectomy (EVT) for acute ischemic stroke due to large vessel occlusion remains debated. In this study, we analyzed the cost-effectiveness of EVT alone versus intravenous alteplase before EVT in patients directly admitted to EVT-capable stroke centers from the Dutch health care payer perspective. METHODS: A decision analysis was performed using a Markov model with 15-year simulated follow-up to estimate total costs, quality-adjusted life years, and an incremental cost-effectiveness ratio of intravenous alteplase before EVT compared with EVT alone. A hypothetical cohort of 10 000 patients with large vessel occlusion aged 70 years was run in Monte Carlo simulation. Functional outcome of each treatment was derived from pooled results of 6 randomized controlled trials (RCTs). Uncertainty was assessed by probabilistic analyses, scenario analyses, and 1-way sensitivity analyses. RESULTS: Using functional outcomes obtained from 6 RCTs (intention-to-treat population), intravenous alteplase before EVT resulted in 0.05 quality-adjusted life years gained at an additional $2817 compared with EVT alone, resulting in the incremental cost-effectiveness ratio of $62 287. Probabilistic analyses showed that intravenous alteplase before EVT had a probability of 45% and 54%, respectively, of being cost-effective at the $52 500 and $84 000 thresholds. Restricting functional outcomes from our post hoc modified as-treated analysis of 6 RCTs (scenario 1), European RCTs (scenario 2), or a Dutch RCT (scenario 3), intravenous alteplase before EVT was cost-effective in 64%, 81%, and 50% of simulations at the $52 500 threshold, and 79%, 91%, and 67% of simulations at the $84 000 threshold. CONCLUSIONS: Intravenous alteplase before EVT was not cost-effective in patients with large vessel occlusion in the Netherlands at the $52 500 threshold but possibly cost-effective at the $84 000 threshold. Variable functional outcomes at 3 months based on different trial populations affected the cost-effectiveness of intravenous alteplase before EVT.

First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trial Data.

PURPOSE: Nivolumab plus relatlimab and nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of the phase II/III RELATIVITY-047 and phase III CheckMate 067 trials, respectively. As no head-to-head trial comparing these regimens exists, an indirect treatment comparison was conducted using patient-level data from each trial. METHODS: Inverse probability of treatment weighting (IPTW) adjusted for baseline characteristic differences. Minimum follow-ups (RELATIVITY-047, 33 months; CheckMate 067, 36 months) were selected to best align assessments. Outcomes included progression-free survival (PFS), confirmed objective response rate (cORR), and melanoma-specific survival (MSS) per investigator; overall survival (OS); and treatment-related adverse events (TRAEs). A Cox regression model compared PFS, OS, and MSS. A logistic regression model compared cORRs. Subgroup analyses were exploratory. RESULTS: After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n = 339) and nivolumab plus ipilimumab (n = 297). Nivolumab plus relatlimab demonstrated similar PFS (hazard ratio [HR], 1.08 [95% CI, 0.88 to 1.33]), cORR (odds ratio, 0.91 [95% CI, 0.73 to 1.14]), OS (HR, 0.94 [95% CI, 0.75 to 1.19]), and MSS (HR, 0.86 [95% CI, 0.67 to 1.12]) to nivolumab plus ipilimumab. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab with acral melanoma, BRAF-mutant melanoma, and lactate dehydrogenase >2 × upper limit of normal, but were limited by small samples. Nivolumab plus relatlimab was associated with fewer grade 3-4 TRAEs (23% v 61%) and any-grade TRAEs leading to discontinuation (17% v 41%). CONCLUSION: Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most-but not all-subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.

Interrogating basal ganglia circuit function in people with Parkinson's disease and dystonia.

Background: The dichotomy between the hypo- versus hyperkinetic nature of Parkinson's disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. Methods: Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials. Results: GPi neurons were slower, bustier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression. Conclusions: We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses. Funding: This project was made possible with the financial support of Health Canada through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and of the Azrieli Foundation (LM), as well as a grant from the Banting Research Foundation in partnership with the Dystonia Medical Research Foundation (LM).

Left Atrial Appendage Opacification on Cardiac Computed Tomography in Acute Ischemic Stroke: The Clinical Implications of Slow-Flow.

BACKGROUND: Left atrial appendage (LAA) slow-flow may increase the risk of ischemic stroke. We studied LAA attenuation on cardiac computed tomography in patients with acute ischemic stroke. METHODS AND RESULTS: We used data from a prospective cohort of patients with acute ischemic stroke undergoing cardiac computed tomography during the acute stroke imaging protocol. We compared characteristics, functional outcome (modified Rankin scale: higher scores indicating worse outcome), stroke recurrence and major adverse cardiovascular events after 2-year follow-up between patients with LAA thrombus (filling defect<100 Hounsfield Unit (HU)), slow-flow (filling defect ≥100 HU) and normal filling. Of 421 patients, 31 (7%) had LAA thrombus, 69 (16%) slow-flow, and 321 (76%) normal filling. Patients with thrombus or slow-flow more often had known atrial fibrillation compared with normal filling (45%, 39%, and 9%, P<0.001). Patients with thrombus had higher National Institutes of Health Stroke Scale-scores compared with slow-flow and normal filling (18 [interquartile range, 9-22], 6 [interquartile range, 3-17], and 5 [interquartile range, 2-11], P<0.001). Compared with normal filling, there was no difference with slow-flow in functional outcome (median modified Rankin scale, 3 versus 2; acOR 0.8 [95% CI, 0.5-1.4]), stroke recurrence (adjusted hazard ratio, 0.8 [95% CI, 0.3-1.9]) or major adverse cardiovascular events (adjusted hazard ratio, 1.2 [95% CI, 0.7-2.1]), while patients with thrombus had worse functional outcome (median modified Rankin scale, 6, acOR, 3.3 [95% CI, 1.5-7.4]). In cryptogenic stroke patients (n=156) slow-flow was associated with stroke recurrence (27% versus 6%, aHR, 4.1 [95% CI, 1.1-15.7]). CONCLUSIONS: Patients with slow-flow had similar characteristics to patients with thrombus, but had less severe strokes. Slow-flow was not significantly associated with functional outcome or major adverse cardiovascular events, but was associated with recurrent stroke in patients with cryptogenic stroke.

Diurnal High Temperatures Affect the Physiological Performance and Fruit Quality of Highbush Blueberry (Vaccinium corymbosum L.) cv. Legacy.

In this study, the physiological performance and fruit quality responses of the highbush blueberry (Vaccinium corymbosum) cultivar Legacy to high temperatures (HTs) were evaluated in a field experiment. Three-year-old V. corymbosum plants were exposed to two temperature treatments between fruit load set and harvest during the 2022/2023 season: (i) ambient temperature (AT) and (ii) high temperature (HT) (5 °C ± 1 °C above ambient temperature). A chamber covered with transparent polyethylene (100 µm thick) was used to apply the HT treatment. In our study, the diurnal temperature was maintained with a difference of 5.03 °C ± 0.12 °C between the AT and HT treatments. Our findings indicated that HT significantly decreased CO2 assimilation (Pn) by 45% and stomatal conductance (gs) by 35.2% compared to the AT treatment. By contrast, the intercellular CO2 concentration (Ci) showed higher levels (about 6%) in HT plants than in AT plants. Fruit quality analyses revealed that the fruit weight and equatorial diameter decreased by 39% and 13%, respectively, in the HT treatment compared to the AT treatment. By contrast, the firmness and total soluble solids (TSS) were higher in the HT treatment than in the AT treatment. Meanwhile, the titratable acidity showed no changes between temperature treatments. In our study, Pn reduction could be associated with stomatal and non-stomatal limitations under HT treatment. Although these findings improve our understanding of the impact of HTs on fruit growth and quality in V. corymbosum, further biochemical and molecular studies are need.

Physiological, transcriptomic and metabolomic insights of three extremophyte woody species living in the multi-stress environment of the Atacama Desert.

MAIN CONCLUSIONS: In contrast to Neltuma species, S. tamarugo exhibited higher stress tolerance, maintaining photosynthetic performance through enhanced gene expression and metabolites. Differentially accumulated metabolites include chlorophyll and carotenoids and accumulation of non-nitrogen osmoprotectants. Plant species have developed different adaptive strategies to live under extreme environmental conditions. Hypothetically, extremophyte species present a unique configuration of physiological functions that prioritize stress-tolerance mechanisms while carefully managing resource allocation for photosynthesis. This could be particularly challenging under a multi-stress environment, where the synthesis of multiple and sequential molecular mechanisms is induced. We explored this hypothesis in three phylogenetically related woody species co-occurring in the Atacama Desert, Strombocarpa tamarugo, Neltuma alba, and Neltuma chilensis, by analyzing their leaf dehydration and freezing tolerance and by characterizing their photosynthetic performance under natural growth conditions. Besides, the transcriptomic profiling, biochemical analyses of leaf pigments, and metabolite analysis by untargeted metabolomics were conducted to study gene expression and metabolomic landscape within this challenging multi-stress environment. S. tamarugo showed a higher photosynthetic capacity and leaf stress tolerance than the other species. In this species, a multifactorial response was observed, which involves high photochemical activity associated with a higher content of chlorophylls and ß-carotene. The oxidative damage of the photosynthetic apparatus is probably attenuated by the synthesis of complex antioxidant molecules in the three species, but S. tamarugo showed the highest antioxidant capacity. Comparative transcriptomic and metabolomic analyses among the species showed the differential expression of genes involved in the biosynthetic pathways of key stress-related metabolites. Moreover, the synthesis of non-nitrogen osmoprotectant molecules, such as ciceritol and mannitol in S. tamarugo, would allow the nitrogen allocation to support its high photosynthetic capacity without compromising leaf dehydration tolerance and freezing stress avoidance.

Microbial nitrogen bubble formation in porous media.

Microbially induced nitrogen (N2) gas bubbles can desaturate subsurface areas and thus have been considered as an alternative ground improvement technique for mitigating soil liquefaction potential caused by earthquakes. However, the detailed mechanisms of subsurface N2 bubbles are not well understood and remain a subject of ongoing research. In this study, a transparent microfluidic device was utilized to mimic biological N2 gas bubble formation by nitrate-reducing bacteria and to visually characterize the entire process. During N2 gas formation, a limited number of bubble nucleation sites were identified, which gradually expanded upward through the preferential pore channels. N2 gas bubbles tended to create interconnected gas pockets rather than existing as evenly distributed small gas cavities. The degree of water saturation gradually reduced over a week as the bubbles were produced. The gas ganglia repeatedly grew until they reached the top boundary, which triggered a drastic expulsion of bubbles by ebullition. Despite fluctuations in saturation level, the residual saturation was maintained at around 73 %. Comparative experimental case studies of CO2 gas bubble formation were conducted to identify contrasting gas formation mechanisms. CO2 gas bubbles were generated via the abiotic decompression of a supersaturated CO2 solution under two distinct rates of pressure reduction. Rapid CO2 bubble formation led to uniform nucleation and 41 % residual saturation, while slower formation yielded 35 % due to stable liquid displacement by the gas front. This study highlights the potential of the microfluidic device as an experimental tool for visualizing subsurface gas formation mechanisms. The insights gained could further enhance and optimize geotechnical applications involving gas formation in highly saturated soils.

Elucidating the impact of environmental factors on the growth of Colletotrichum coccodes strains isolated from potato tubers in Great Britain.

Black dot and silver scurf caused by Colletotrichum coccodes and Helminthosporium solani, respectively, are tuber blemish diseases affecting quality in the fresh and pre-pack potato industry. In the last 20 years, the importance of high-quality tuber appearance has increased considerably due to the growing demand for washed and pre-packed potatoes in the UK. Changing climate characterised by rising temperatures and wetter summers is a threat as this will favour the development of pathogens such as C. coccodes in the soil increasing the risk of food spoilage. Moreover, both diseases can develop not only in the field but also after harvest, with postharvest storage temperatures being a crucial factor in controlling fungal growth. Furthermore, anecdotal evidence showed differences on the aggressiveness of black dot depending on its origin (i.e. England and Scotland) on potato tubers. Silver scurf and black dot are difficult to differentiate as they present similar phenotypes characterised by silvery lesions making it challenging for managers to take the necessary corrective action during storage. Hence, the aim of this study was to give a general insight into the ecological conditions affecting the establishment of the causal agent of potato black dot in the field, and black dot and silver scurf during the supply chain. Therefore, invitro experiments were designed to study the growth rate and lag times simulating both scenarios respectively: on soil extract agar (SEA) media at different temperatures (4, 11, 15 °C) and matric potentials (control [unmodified] and - 1.4 MPa [modified]); and on natural potato dextrose agar (NPDA) for different temperatures (4, 11, 15 and 20 °C) at 99 % relative humidity (RH) for 25 days. When simulating the field environment, drier conditions (matric potential = -1.4 MPa) reduced fungal growth for both isolates by 0.1 cm day-1 at the temperature of 15 °C, suggesting temperature as the main limiting factor for the growth of C. coccodes in the soil. The causal agent of black dot exhibited a faster growth rate under retailer-like conditions (i.e., 15 °C) compared to H. solani. Understanding the environmental influence on both the pathogen and the crop is vital for proper disease management to help reduce food loss and waste.

Clinical evaluation of a new chemically-cured bulk-fill composite in posterior restorations: 6-month multicenter double-blind randomized clinical trial.

OBJECTIVE: To evaluate the postoperative sensitivity (POS), as well as the clinical performance of posterior restorations using a new chemically-cured bulk-fill composite (Stela Automix and Stela Capsule, SDI) comparing with a light-cured bulk-fill composite after 6 months. METHODS: Fifty-five participants with at least three posterior teeth needing restoration were recruited. A total of 165 restorations were performed on Class I or Class II cavities. After the application of Stela primer, the chemically-cured composite (Stela Automix or Stela Capsule) was inserted. For the light-cured composite group, a universal adhesive (Scotchbond Universal) was applied with a bulk-fill composite (Filtek One). Participants were evaluated for spontaneous and stimulated POS in the baseline, after 48 h, 7 days, and 6 months. Additionally, each restoration was assessed using the updated version of FDI criteria after 6 months. The differences in the proportions of the groups were compared by Cochran test statistics (α = 0.05). RESULTS: Both chemically-cured composites showed a lower risk of POS compared to the light-cured composite at baseline and up to 48 h (p < 0.04). A significantly lower surface luster and texture was observed for the Stela Capsule composite compared to the light-cured bulk-fill composite (baseline and 6 months; p = 0.03). A significant color mismatch was observed for the light-cured bulk-fill composite compared to the chemically-cured composites (baseline and 6 months; p = 0.03). No significant differences were observed in any other item evaluations (p > 0.05). CONCLUSION: Chemically-cured composites exhibit lower postoperative sensitivity and less color mismatch compared to a light-cured bulk-fill composite after 6 months of clinical service. CLINICAL SIGNIFICANCE: The chemically-cured composites appear to be an appealing option for restoring posterior teeth, as they exhibit lower postoperative sensitivity compared to a light-cured bulk-fill composite, both at baseline and up to 48 h, and less color mismatch.

A randomized multicenter trial of a chronic disease management intervention for decompensated cirrhosis. The Australian Liver Failure (ALFIE) trial.

BACKGROUND AND AIMS: Improving the care of decompensated cirrhosis is a significant clinical challenge. The primary aim of this trial was to assess the efficacy of a chronic disease management (CDM) model to reduce liver-related emergency admissions (LREA). The secondary aims were to assess model effects on quality-of-care and patient-reported outcomes. APPROACH AND RESULTS: The study design was a 2-year, multicenter, randomized controlled study with 1:1 allocation of a CDM model versus usual care. The study setting involved both tertiary and community care. Participants were randomly allocated following a decompensated cirrhosis admission. The intervention was a multifaceted CDM model coordinated by a liver nurse. A total of 147 participants (intervention=75, control=71) were recruited with a median Model for End-Stage Liver Disease score of 19. For the primary outcome, there was no difference in the overall LREA rate for the intervention group versus the control group (incident rate ratio 0.89; 95% CI: 0.53-1.50, p=0.666) or in actuarial survival (HR=1.14; 95% CI: 0.66-1.96, p=0.646). However, there was a reduced risk of LREA due to encephalopathy in the intervention versus control group (HR=1.87; 95% CI: 1.18-2.96, p=0.007). Significant improvement in quality-of-care measures was seen for the performance of bone density (p<0.001), vitamin D testing (p<0.001), and HCC surveillance adherence (p=0.050). For assessable participants (44/74 intervention, 32/71 controls) significant improvements in patient-reported outcomes at 3 months were seen in self-management ability and quality of life as assessed by visual analog scale (p=0.044). CONCLUSIONS: This CDM intervention did not reduce overall LREA events and may not be effective in decompensated cirrhosis for this end point.

Comparing levoglucosan and mannosan ratios in sediments and corresponding aerosols from recent Australian fires.

The monosaccharide anhydrides levoglucosan, mannosan, and galactosan are known as 'fire sugars' as they are powerful proxies used to trace fire events. Despite their increasing use, their application is not completely understood, especially in the context of tracing past fire events using sediment samples. There are many uncertainties about fire sugar formation, partitioning, transport, complexation, and stability along all stages of the source-to-sink pathway. While these uncertainties exist, the efficacy of fire sugars as fire tracers remains limited. This study compared high-resolution fire sugar fluxes in freshwater sediment cores to known fire records in Tasmania, Australia. Past fire events correlated with fire sugar flux increases down-core, with the magnitude of the flux inversely proportional to the distance of the fires from the study site. For the first time, fire sugar ratios (levoglucosan/mannosan, L/M) in aerosols were compared with those in sediments from the same time-period. The L/M ratio in surface sediments (1.42-2.58) were significantly lower than in corresponding aerosols (5.08-15.62). We propose two hypotheses that may explain the lower average L/M of sediments. Firstly, the degradation rate of levoglucosan is higher than mannosan in the water column, sediment-water interface, and/or sediment. Secondly, the L/M ratio of non-atmospheric emissions during fires may be lower than that of atmospheric emissions from the same fire. Due to the uncertainties about transport partitioning (atmospheric versus non-atmospheric emissions) and fire sugar degradation along all stages of the source-to-sink pathway, we advise caution when inferring vegetation type (e.g. softwood, hardwood, or grasses) based purely on fire sugar ratios in sediments (e.g. L/M ratio). Future investigations are required to increase the efficacy of fire sugars as a complimentary, or standalone, fire tracer in sediments.

Species specific responses to stressors hamper Trichoptera recovery.

Worldwide, aquatic biodiversity is severely threatened as a result of anthropogenic pressures such as pollution, habitat destruction and climate change. Widescale legislation resulted in reduced nutrient- and pesticide loads, and restoration measures allowed modest recovery of freshwater biodiversity. However, from 2010 onwards, recovery in the otherwise unrestored aquatic habitats stagnated. The aim of the present study was therefore to reveal long-term trends in aquatic biodiversity in an anthropogenic landscape and to explain the observed patterns. To this end, over 40 years of biomonitoring data of the indicative taxa group Trichoptera (caddisflies), with an exceptionally high spatial and temporal resolution, was employed. Periods of recovery, stagnation, and decline were delineated using linear and non-linear modelling approaches. Subsequently, species were grouped based on abundance patterns over time and this grouping was used to ascertain species-specific responses to anthropogenic stressors using a trait-based approach. Richness and abundance of all Trichoptera jointly, as well as of the five most abundant and the remaining 136 species, significantly increased from 1980 to significant breakpoints from 2010 onwards, after which these metrics, except the abundances of the 5 most abundant, declined significantly. Trend-based species groupings were not significantly explained by biological traits or ecological preferences. However, Trichoptera species increasing in abundance were less sensitive to climate change and poor water quality, or concerned sensitive species which benefited from restoration measures. Species with stable or declining abundances showed higher sensitivity to climate change. The Trichoptera declining in abundance indicated that conditions in non-protected or restored habitats did not improve due to climate change on top of the other anthropogenic pressures. These observations reinforce the need for increased efforts to improve the only moderately restored water- and habitat quality in anthropogenic landscapes to halt further aquatic ecosystem degradation and to turn biodiversity losses again into recoveries.