The potentiality of reactive membranes for post combustion CO2 capture

CO2 industrial emissions have a severe impaction on the global warming due the important CO2 greenhouse effect. Post combustion gases represent one of the largest industrial source of CO2 emitted to the atmosphere, currently 30 gigatonsper year. CO2 Flue gas composition varies widely from 4 to 30% depending on its origin. In order to capture and valorise CO2, efficient processes with high capture ratio, high selectivity and low energetic footprint must be developed. Among the process used for CO2 recovery and concentration, membrane separation appears as a promising option. Membranes are environmentally friendly and have high potential for breakthroughs in energy consumption and overall cost, are solvent-free and are compatible for retrofit strategy. However, the CO2 purity limitations with commercial membrane or the actual energy requirement limit the use of membranes in CO2 capture. In order to improve membrane separation performance, Facilitated Transport Membranes (FTM) have been recently developed such as the Fixed Site Carrier Membrane (FSCM based on amine carrier fixed by covalent bond inside the dense polymeric membrane). In this case, facilitated transport is specific to CO2 mass transfer. Amine reacts with CO2 in presence of high relative humidity and makes a new complex, HCO3-. The anion crosses through the membrane by hopping mechanism. In the low pressure permeate side, the reversible reaction occurs and CO2 is released. Please click Additional Files below to see the full abstract

LineUp: Visual Analysis of Multi-Attribute Rankings

Rankings are a popular and universal approach to structuring otherwise unorganized collections of items by computing a rank for each item based on the value of one or more of its attributes. This allows us, for example, to prioritize tasks or to evaluate the performance of products relative to each other. While the visualization of a ranking itself is straightforward, its interpretation is not, because the rank of an item represents only a summary of a potentially complicated relationship between its attributes and those of the other items. It is also common that alternative rankings exist which need to be compared and analyzed to gain insight into how multiple heterogeneous attributes affect the rankings. Advanced visual exploration tools are needed to make this process efficient. In this paper we present a comprehensive analysis of requirements for the visualization of multi-attribute rankings. Based on these considerations, we propose LineUp - a novel and scalable visualization technique that uses bar charts. This interactive technique supports the ranking of items based on multiple heterogeneous attributes with different scales and semantics. It enables users to interactively combine attributes and flexibly refine parameters to explore the effect of changes in the attribute combination. This process can be employed to derive actionable insights as to which attributes of an item need to be modified in order for its rank to change. Additionally, through integration of slope graphs, LineUp can also be used to compare multiple alternative rankings on the same set of items, for example, over time or across different attribute combinations. We evaluate the effectiveness of the proposed multi-attribute visualization technique in a qualitative study. The study shows that users are able to successfully solve complex ranking tasks in a short period of time.Engineering and Applied Science

Key Components for Antibiotic Dose Optimization of Sepsis in Neonates and Infants.

Sepsis in neonates and infants remains a major cause of death despite a decline in child mortality and morbidity over the last decades. A key factor in further reducing poor clinical outcomes is the optimal use of antibiotics in sepsis management. Developmental changes such as maturation of organ function and capacity of drug metabolizing enzymes can affect the pharmacokinetic profile and therefore the antibiotic exposure and response in neonates and infants. Optimal antibiotic treatment of sepsis in neonates and young infants is dependent on several key components such as the determination of treatment phase, the administered dose and the resulted drug exposure and microbiological response. During the initial phase of suspected sepsis, the primary focus of empirical treatment is to assure efficacy. Once bacterial infection as the cause of sepsis is confirmed the focus shifts toward a targeted treatment, ensuring an optimal balance between efficacy and safety. Interpretation of antibiotic exposure and microbiological response in neonates and infants is multifaceted. The response or treatment effect can be determined by the microbiological parameters (MIC) together with the characteristics of the pathogen (time- or concentration dependent). The antibiotic response is influenced by the properties of the causative pathogen and the unique characteristics of the vulnerable patient population such as reduced humoral response or reduced skin barrier function. Therapeutic drug monitoring (TDM) of antibiotics may be used to increase effectiveness while maximizing safety and minimizing the toxicity, but requires expertise in different fields and requires collaborations between physicians, lab technicians, and quantitative clinical pharmacologists. Understanding these clinical, pharmacological, and microbiological components and their underlying relationship can provide a scientific basic for proper antibiotic use and reduction of antibiotic resistance in neonates and infants. This highlights the necessity of a close multidisciplinary collaboration between physicians, pharmacists, clinical pharmacologists and microbiologist to assure the optimal utilization of antibiotics in neonates and young infants

Pharmacometric Analysis of Intranasal and Intravenous Nalbuphine to Optimize Pain Management in Infants

Objectives: The objective of this pharmacometric (PMX) study was to (i) characterize population pharmacokinetics (PPK) and exposure-pain response associations following intranasal (0.1 mg/kg) or intravenous (IV, 0.05 mg/kg) administration of nalbuphine, with the goal to (ii) evaluate strategies for optimized dosing and timing of painful interventions in infants 1-3 months old. Methods: PPK analysis of nalbuphine serum concentrations, prospectively collected 15, 30, and between 120 and 180 min post-dose, utilizing the software package Monolix. The final PPK model was applied to derive individual time-matched concentration predictions for each pain assessment (Neonatal Infant Pain Score, NIPS) after establishment of venous access and urinary catheterization or lumbar puncture. Drug exposure-pain response simulations were performed to evaluate potential benefits of higher doses with respect to a previously proposed target concentration of 12 mcg/L (efficacy threshold). Results: Thirty-eight of 52 study subjects receiving nalbuphine had at least one concentration measurement and were included in the pharmacometric analysis. A two-compartment model with allometric scaling was applied to describe population PK data, with intranasal bioavailability estimated to be 41% (95%CI: 26-56%). Model-based simulations showed that the proposed efficacy threshold (12 mcg/L) is expected to be exceeded with an IV dose of 0.05 mg/kg for 6 min, with 0.1 mg/kg for 30 min and with 0.2 mg/kg for 80 min. This efficacy threshold is not achieved with intranasal doses of 0.1 and 0.2 mg/kg, whereas an intranasal dose of 0.4 mg/kg is expected to exceed such threshold for 30 to 100 min. Conclusion: This PMX study confirmed that bioavailability of intranasal nalbuphine is close to 50%. Exposure-pain response simulations indicated that an intranasal dose of 0.4 mg/kg is required to provide a comparable pain control as achieved with an IV dose of 0.1-0.2 mg/kg. The optimal time window for painful procedures appears to be within the first 30 min after IV administration of 0.1 mg/kg nalbuphine, whereas such procedures should be scheduled 30 min after an intranasal dose of 0.4 mg/kg nalbuphine. Additional clinical studies are warranted to confirm these PMX based recommendations and to further optimize pain management in this vulnerable infant population. Keywords: exposure response; infants; nalbuphine; opioid analgesics; pediatrics; pharmacodynamics; pharmacokinetics

Pharmacokinetics and tolerability of intranasal or intravenous administration of nalbuphine in infants

Objectives: Intranasal nalbuphine could be a safe, efficacious and non-invasive alternative to parenteral pain medication in infants. We aimed to assess pharmacokinetics (PK) and tolerability of intranasal and intravenous nalbuphine administration in infants. Methods: Prospective open-label study including infants 1-3 months of age admitted to the emergency department, receiving nalbuphine for procedural pain management. Patients were alternately allocated to a single nalbuphine dose of 0.05 mg/kg intravenously or 0.1 mg/kg intranasally. Nalbuphine PK samples were collected 15, 30 and 120-180 min after dosing. Area under the concentration time curve (AUC0-Tlast) was calculated by non-compartmental analysis (NCA) and compared by Wilcoxon test. Neonatal Infant Pain Score was assessed during nalbuphine administration and the following interventions: venous access, urinary catheterisation, lumbar puncture. Results: Out of 52 study subjects receiving nalbuphine, 31 were eligible for NCA (11 intravenous, 20 intranasal). Median AUC0-Tlast after 0.05 mg/kg intravenously was 8.7 (IQR: 8.0-18.6) µg×L/hour vs 7.6 (5.4-10.4) µg×L/hour after intranasal administration of 0.1 mg/kg (p=0.091). Maximum serum concentration (Cmax) was observed 30 min after intranasal administration (3.5-5.6 µg/L). During intravenous and intranasal nalbuphine administration, mild to no pain was recorded in 71% and 67% of study subjects, respectively. Conclusion: This is the first study investigating intranasal administration of nalbuphine in infants suggesting an intranasal bioavailability close to 50%. Non-invasive intranasal application was well tolerated. Additional studies are warranted to optimise dosing and timing of interventions as Cmax is delayed by half an hour after intranasal administration. Trial registration number: NCT03059511. Keywords: paediatric emergency medicine; pain

Characterization and Turnover of CD73/IP3R3-positive Microvillar Cells in the Adult Mouse Olfactory Epithelium

The main olfactory epithelium consists of 4 major cell types: sensory neurons, supporting cells, microvillar cells, and basal progenitor cells. Several populations of microvillar olfactory cells have been described, whose properties are not yet fully understood. In this study, we aimed to clarify the classification of microvillar cells by introducing a specific marker, CD73. Furthermore, we investigated the turnover of CD73-microvillar cells during adult life. Using direct and indirect immunofluorescence in adult main olfactory epithelium, we first demonstrate that ecto-5′-nucleotidase (CD73) is a reliable marker for microvillar cells reported previously to express phospholipase C β2 (PLC β2) along with type 3 IP3 receptors (IP3R3) and transient receptor potential channels 6 (TRPC6), as well as for cells labeled by transgenic expression of tauGFP driven by the IP3R3 promoter. The ubiquitous CD73 immunoreactivity in the microvilli of these 2 cell populations indicates that they correspond to the same cell type (CD73-microvillar cell), endowed with a signal transduction cascade mobilizing Ca++ from intracellular stores. These microvillar cells respond to odors, possess a basal process, and do not degenerate after bulbectomy, suggesting that they contribute to cellular homeostasis in the olfactory epithelium. Next, we examined whether CD73-microvillar cells undergo turnover in the adult olfactory epithelium. By combining CD73 immunofluorescence and BrdU pulse labeling, we show delayed BrdU incorporation in a small fraction of CD73-positive microvillar cells, which persists for several weeks after BrdU administration. These findings indicate that CD73-microvillar cells likely differentiate from proliferating progenitor cells and have a slow turnover despite their apical position in the olfactory epithelium. These combined properties are unique among olfactory cells, in line with the possibility that they might regulate cellular homeostasis driven by extracellular ATP and adenosin

Entourage: Visualizing Relationships between Biological Pathways using Contextual Subsets

Biological pathway maps are highly relevant tools for many tasks in molecular biology. They reduce the complexity of the overall biological network by partitioning it into smaller manageable parts. While this reduction of complexity is their biggest strength, it is, at the same time, their biggest weakness. By removing what is deemed not important for the primary function of the pathway, biologists lose the ability to follow and understand cross-talks between pathways. Considering these cross-talks is, however, critical in many analysis scenarios, such as judging effects of drugs. In this paper we introduce Entourage, a novel visualization technique that provides contextual information lost due to the artificial partitioning of the biological network, but at the same time limits the presented information to what is relevant to the analyst’s task. We use one pathway map as the focus of an analysis and allow a larger set of contextual pathways. For these context pathways we only show the contextual subsets, i.e., the parts of the graph that are relevant to a selection. Entourage suggests related pathways based on similarities and highlights parts of a pathway that are interesting in terms of mapped experimental data. We visualize interdependencies between pathways using stubs of visual links, which we found effective yet not obtrusive. By combining this approach with visualization of experimental data, we can provide domain experts with a highly valuable tool. We demonstrate the utility of Entourage with case studies conducted with a biochemist who researches the effects of drugs on pathways. We show that the technique is well suited to investigate interdependencies between pathways and to analyze, understand, and predict the effect that drugs have on different cell types.Engineering and Applied Science

Understanding efficacy-safety balance of biologics in moderate-to-severe pediatric psoriasis

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease affecting both adults and children. To better understand the efficacy-safety profile of biologics in children with moderate-to-severe psoriasis, this study aimed to analyze efficacy and safety data of randomized controlled trials (RCTs) performed in pediatric psoriasis and to compare efficacy outcomes in children with those in adults. METHODS: RCTs investigating biologics in children with moderate-to-severe psoriasis were identified in a systematic literature review. PASI75/90 treatment responses at weeks 11/12 were analyzed comparing biologics with control arms. Serious adverse events (SAEs) were analyzed at the end of each study. Efficacy data from RCTs in adults with psoriasis were selected for the same biologics. Risk ratios (RR) of selected RCTs were pooled together in a statistical random effects model using the inverse variance method. RESULTS: For children, there were 1 etanercept, 2 secukinumab, 1 ixekizumab and 1 ustekinumab placebo-controlled RCTs and 1 adalimumab RCT using methotrexate as reference arm at weeks 11/12. For adults, out of 263 RCTs, 7 adalimumab and 15 etanercept (TNF inhibitors) and 4 ixekizumab and 12 ustekinumab (IL-17 and IL-12/23 inhibitors) RCTs reported PASI75/90 efficacy responses at weeks 11/12. Regarding efficacy, all biologics showed improved PASI responses over control arms. RRs ranges were 2.02-7.45 in PASI75 and 4.10-14.50 in PASI90. The highest PASI75 responses were seen for ustekinumab 0.375 mg/kg (RR = 7.25, 95% CI 2.83-18.58) and ustekinumab 0.75 mg/kg (RR = 7.45, 95% CI 2.91-19.06) in the CADMUS study. The highest PASI90 response was seen for ixekizumab (RR = 14.50, 95% CI 4.82-43.58) in the IXORA-PEDS study. SAE incidences in pediatric and adult arms with biologics were 0 to 3% except for a pediatric arm with adalimumab 0.40 mg/kg (8%). For adults, pooled RR also showed improved PASI responses over placebo for all biologics, with highest PASI75 response observed for ixekizumab (pooled RR = 16.18, 95% CI 11.83-22.14). CONCLUSION: Both adults and children with psoriasis show superior efficacy with biologics compared to control arms after 3 months of treatment with SAE incidences in the low percentages. Additional longer-term clinical studies are warranted to fully understand the overall efficacy-safety profile of biologics in children with moderate-to-severe psoriasis

Age appropriate reference intervals for eight kidney function and injury markers in infants, children and adolescents.

Objectives The use of kidney function and injury markers for early detection of drug-related glomerular or tubular kidney injury in infants, children and adolescents requires age-specific data on reference intervals in a pediatric healthy population. This study characterizes serum values for eight kidney function and injury markers in healthy infants, children and adolescents. Methods A single center prospective observational study was conducted between December 2018 and June 2019. Serum samples from 142 healthy infants, children and adolescents aged between 0 and ≤15 years were collected. Statistical analyses for eight markers (albumin (ALB), β2-microglobulin (B2M), β-trace protein (BTP), creatinine (SCR), cystatin C (CYSC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), uromodulin (URO)) were performed to obtain reference intervals and associations with age, sex and weight were investigated (Pearson correlation, linear and piecewise regression). Results ALB and SCR increased with age (p<0.01), whereas B2M, BTP and KIM-1 values decreased with advancing age (p<0.05) in this healthy pediatric study population. CYSC showed dependency on sex (lower concentration in females) and decreased with age until reaching approximately 1.8 years; thereafter an increase with age was seen. NGAL and URO did not show any age-dependency. Conclusions This study provides age appropriate reference intervals for key serum kidney function and injury markers determined in healthy infants, children and adolescents. Such reference intervals facilitate the interpretation of changes in kidney function and injury markers in daily practice, and allow early detection of glomerular and tubular injury in infancy, childhood and adolescence