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Background and Aim: Fulminant Clostridioides difficile infections (FCDI) account for 8% of cases and substantial healthcare burden. Fecal microbiota transplantation is recommended for recurrent CDI, but emerging data support use for FCDI. We aimed to assess the cost‐effectiveness of a sequential fecal microbiota transplantation (sFMT) protocol for FCDI compared with current standard therapy. Methods: A Markov model simulated patients with FCDI in a 1‐year time horizon. The treatment algorithm for up to three sFMTs, clinical probabilities, and direct costs were used from published sources. Outcomes were quality‐adjusted life years (QALYs) and costs. The healthcare sector perspective was used with a willingness‐to‐pay threshold of $100 000 per QALY. Results: Sequential fecal microbiota transplantation (FMT) for FCDI was associated with lower overall cost ($28 309 vs $33 980) and higher QALY (0.765 vs 0.686) compared with standard therapy. sFMT is cost‐effective in 100% of iterations. sFMT remained cost‐effective at cure rates > 44.8% for the first FMT and at stool preparation cost < $6944 per instillation. We find a wide range of efficacies for the first versus second FMT at which sFMT is still preferred. Value of information analysis estimates the expected value of perfect information to be low at $1.89 per person, quantified with net monetary benefit. Conclusions: An sFMT strategy strongly dominates standard therapy, with lower cost and higher QALY. Sensitivity analysis demonstrates benefit even if FMT cure rates are lower than expected and when multiple FMTs are required. FMT material in 2020 was priced at $1695 per treatment but remains cost‐effective at a much higher cost. [ABSTRACT FROM AUTHOR]

Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT. [ABSTRACT FROM AUTHOR]

[Display omitted] • Thermo-mechanical treatment for sustainable upcycling of mixed recycled aggregates. • Aggregate treated at temperature of 700 °C shows best aggregate characteristics. • Treated aggregate shows better workability (166.6%) than normal aggregates. • Treated aggregate shows similar strength (93.7%–99.9%) than normal aggregates. • Renewable energy can bring down cost and carbon emission below natural aggregate. The study investigates thermo-mechanical treatment for mixed recycled aggregates (MRA). Six treated aggregates were prepared by heating MRA between 300 °C and 800 °C, followed by 100 abrasion cycles. The thermo-mechanical treatment causes loss in the adhered mortar and improves aggregate crushing, impact and abrasion value up to 700 °C. Concrete prepared with MRA treated at 700 °C, as compared to natural aggregates, shows higher workability (166.67%) and comparable mechanical strength, i.e., compressive (93.72%), flexural (99.94%) and split tensile (97.87%). The sustainability assessment shows that treating MRA with renewable energy can have lower economic costs (89.36%) and carbon emissions (58.05%) than manufacturing natural aggregates. [ABSTRACT FROM AUTHOR]

Electrochemical ceramic membrane reactors (ECMRs) with their unique ability to efficiently couple electrical, chemical, and thermal energy sectors can be a large part of the transition toward renewable energies and defossilized economies. ECMRs utilize ceramic conductors to extract or distribute oxide ions or protons – directly controlled by an external electric current. This article gives an overview of ECMR properties along with the functionalities and advantages. For many reactions, e.g., the direct synthesis of ammonia, ECMRs are not available at the preferred temperature range of 300 – 550 °C. To evidence the possibility of such reactors, functional materials are reviewed. A simple thermodynamic methodology is proposed to determine the suitability of reactions for particular combinations of coupled energy sectors. [ABSTRACT FROM AUTHOR]

Understanding mechanisms in lineage differentiation is critical for organ development, pathophysiology and oncogenesis. To determine whether microRNAs (miRNA) may serve as drivers or adjuncts in hepatic differentiation, we studied human embryonic stem cell-derived hepatocytes and primary hepatocytes representing fetal or adult stages. Model systems were used for hepatic lineage advancement or regression under culture conditions with molecular assays. Profiles of miRNA in primary fetal and adult hepatocytes shared similarities and distinctions from pluripotent stem cells or stem cell-derived early fetal-like hepatocytes. During phenotypic regression in fetal or adult hepatocytes, miRNA profiles oscillated to regain stemness-associated features that had not been extinguished in stem cell-derived fetal-like hepatocytes. These oscillations in stemness-associated features were not altered in fetal-like hepatocytes by inhibitory mimics for dominantly-expressed miRNA, such as hsa-miR-99b, -100, -214 and -221/222. The stem cell-derived fetal-like hepatocytes were permissive for miRNA characterizing mature hepatocytes, including mimics for hsa-miR-122, -126, -192, -194 and -26b, although transfections of the latter did not advance hepatic differentiation. Examination of genome-wide mRNA expression profiles in stem cell-derived or primary fetal hepatocytes indicated targets of highly abundant miRNA regulated general processes, e.g., cell survival, growth and proliferation, functional maintenance, etc., without directing cell differentiation. Among upstream regulators of gene networks in stem cell-derived hepatocytes included HNF4A, SNAI1, and others, which affect transcriptional circuits directing lineage development or maintenance. Therefore, miRNA expression oscillated in response to microenvironmental conditions, whereas lineage-specific transcriptional regulators, such as HNF4A, were necessary for directing hepatic differentiation. This knowledge will be helpful for understanding the contribution of stem cells in pathophysiological states and oncogenesis, as well as for applications of stem cell-derived hepatocytes. [ABSTRACT FROM AUTHOR]

Cerebral malaria (CM) presents as an encephalopathy and is due to infection with Plasmodium falciparum. Patients are comatose, often with fever, recurrent seizures and this condition is associated with a high mortality rate. The etiology of the coma and seizures are poorly understood. Circulating small molecules and lipids have bioactive functions and alterations in their concentrations have been implicated in seizure disorders and other forms of encephalopathy. We carried out a comprehensive analysis of blood metabolites during CM to explore a biochemical basis of this encephalopathy. A paired metabolomics analysis was performed on the plasma samples of Malawian children (n = 11) during CM and at convalescence thirty days later, to identify differentially abundant molecules associated with CM. We also report plasma molecules associated with CM mortality (n = 4) compared to survival (n = 19). Plasma metabolites were identified through ultra high performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry to maximize compound detection and accuracy and then compared to a library for identification. We detected a total of 432 small molecules in the plasma and 247 metabolites were significantly differentially abundant between CM and convalescence (p < 0.05, FDR < 0.10). These represented global changes across many classes of molecules including lipids, amino acids and hemoglobin metabolites. We observed significant changes in molecules that could impact neurologic function during CM; these include increased levels of kynurenate and decreased indolepropionate, glutamate, arginine and glutamine. Moreover, 1-methylimidazoleacetate, kyurenate, arachidonic acid and dimethylarginine were associated with mortality (p < 0.05, fold change > 1.2). These results highlight the broad changes in blood chemistry during CM. We have identified metabolites that may impact central nervous system physiology and disease outcomes and can be further explored for their mechanistic roles into the pathophysiology of CM. [ABSTRACT FROM AUTHOR]

A large number of wastes and naturally occurring resources have been recognized as Supplementary cementitious materials (SCM) for their role in clinker substitution and the resulting low carbon cement. While helpful for optimum utilization, existing literature fails to help stakeholders in selecting a suitable SCM. To address this challenge, the manuscript reviews over 20 different SCMs investigated in India for their availability, characteristics (physical, chemical, mineral and morphological), effect on the properties of concrete (workability, strength and durability) and environmental impact. The study shows that over 380 Mtpa of SCMs are generated in India, more than the estimated need of 105 Mtpa. The asymmetrical distribution of SCM availability call for alternative SCMs in some regions (12.22 Mtpa shortage) and high-volume utilization in other regions (131.88 Mtpa excess). The review uses a characteristics-based classification to identify SCMs with similar traits and understand their effects on concrete. Results show that SCMs having particle sizes similar to cement and spherical morphology improve the workability of concrete. Similarly, SCMs with very-fine particle size (specific surface area greater than 1200 m2/kg) and high Ca content (more than 10% Ca in chemical composition) improve concrete's compressive, flexural, and split tensile strength. The addition of SCM also improves durability against chloride ion penetration and wetting and drying cycles. Recommendations have also been made to guide stakeholders towards the suitable application of different SCMs. Multi-blended cement and long-term environmental impact have also been discussed to help stakeholders select a sustainable SCM. [Display omitted] • Review of over 20 SCMs, their availability, characteristics and effect on concrete. • SCMs grouped by physical, chemical, mineral and morphological characteristics. • Characteristic groups have similar effect on concrete, than similar origin source. • Characterization based approach for identifying suitable application of SCM. • Local waste utilization and multi blend cement for improved sustainability. [ABSTRACT FROM AUTHOR]

We have developed a software package named PEAS to facilitate analyses of large data sets of single nucleotide polymorphisms (SNPs) for population genetics and molecular phylogenetics studies. PEAS reads SNP data in various formats as input and is versatile in data formatting; using PEAS, it is easy to create input files for many popular packages, such as STRUCTURE, frappe, Arlequin, Haploview, LDhat, PLINK, EIGENSOFT, PHASE, fastPHASE, MEGA and PHYLIP. In addition, PEAS fills up several analysis gaps in currently available computer programs in population genetics and molecular phylogenetics. Notably, (i) It calculates genetic distance matrices with bootstrapping for both individuals and populations from genome-wide high-density SNP data, and the output can be streamlined to MEGA and PHYLIP programs for further processing; (ii) It calculates genetic distances from STRUCTURE output and generates MEGA file to reconstruct component trees; (iii) It provides tools to conduct haplotype sharing analysis for phylogenetic studies based on high-density SNP data. To our knowledge, these analyses are not available in any other computer program. PEAS for Windows is freely available for academic users from . [ABSTRACT FROM AUTHOR]

Growing concern over the environment has led the Indian Construction Industry towards Sustainable Development and Circular Economy. As a part of the solution, a part of clinker, the primary constituent of cement, is replaced by industrial by-product, waste ash, or similar fine materials, collectively known as Supplementary Cementitious Materials or SCM. Several organizations are actively engaged towards development, dissemination and promotion of technologies on SCM utilization. In Indian construction industry utilization of SCM is contingent on the existing legal framework, which includes relevant directives, standards, and technical guidelines. Literature shows directives have the highest influence followed by standards on the utilization of SCMs. Although provisions exist for utilization of SCMs in the absence of a relevant standard, they are rarely utilized. This makes knowledge of existing legal framework imperative for integrating studies on SCM utilization with industrial practices and subsequent development in the legal framework. The manuscript provides a state of the art review on existing legal policies, organizations influencing SCM utilization and an overview of development pattern. The manuscript will serve as a support tool for industry professionals, at the time of industrial application of SCM, and as an outline for the research community, for analysis of legal barriers. The manuscript will promote the utilization of SCM in the Indian construction industry through a better understanding of legal barriers. Image 1 • SCM – overview, environmental befits and application challenges in India. • Legal perspective (standards, directives & guidelines) for SCM utilization in India. • Overview of organizations with significant impact on SCM utilization in India. • Analysis of development of SCM use as a sustainable construction practice in India. • Solutions promoting use of SCMs as clean technology in Indian Construction Industry. [ABSTRACT FROM AUTHOR]

In 2018, with the internet being treated as a utility on equal grounds as clean water or air, the underground malicious software economy is flourishing with an influx of growth and sophistication in the attacks. The use of malicious documents has increased rapidly in the last five years along with a spectrum of attacks. They offer flexibility in document structure with numerous features for attackers to exploit. Despite efforts from industry and research communities, this remains a viable security threat. In this paper, a broad classification of malicious documents based attacks is provided along with a detailed description of the attack opportunities available using Portable Document Format (PDF) and Office documents. Detailed structures of both file formats, state of the art tools as well as the current research in automatic detection methods have been discussed. [ABSTRACT FROM AUTHOR]

Background: Cerebral malaria (CM) remains a significant cause of morbidity and mortality in children in sub-Saharan Africa. CM mortality has been associated with increased brain volume, seen on neuroimaging studies. Methods: To examine the potential role of blood metabolites and inflammatory mediators in increased brain volume in Malawian children with CM, an association study was performed between plasma metabolites, cytokine levels and phospholipase A2 (PLA2) activity with brain volume. Results: The metabolomics analysis demonstrated arachidonic acid and other lysophospholipids to be positively associated with brain swelling. These lipids are products of the PLA2 enzyme and an association of plasma PLA2 enzymatic activity with brain swelling was confirmed. TNFα, which can upregulate PLA2 activity, was associated with brain volume. In addition, CCL2 and IL-8 were also associated with brain volume. Some of these cytokines can alter endothelial cell tight junction proteins and increase blood brain barrier permeability. Conclusions: Taken together, paediatric CM brain volume was associated with products of the PLA2 pathway and inflammatory cytokines. Their role in causality is unknown. These molecules will need to undergo testing in vitro and in animal models to understand their role in processes of increased brain volume. These observations provide novel data on host physiology associated with paediatric CM brain swelling, and may both inform pathogenesis models and suggest adjunct therapies that could improve the morbidity and mortality associated with paediatric CM. [ABSTRACT FROM AUTHOR]

Background: Larger caliber lumen-apposing stents (LAMSs) have been increasingly used in the management of pancreatic fluid collections, specifically when solid debris is present; however, their advantages over smaller caliber plastic stents in the management of pancreatic pseudocysts are unclear. The aim of this study was to investigate the safety and efficacy of LAMS specifically in the management of pancreatic pseudocysts compared with double-pigtail plastic stents (DPPSs).Methods: We performed a multicenter, international, retrospective study between January 2012 and August 2016. A total of 205 patients with a diagnosis of pancreatic pseudocysts were included, 80 patients received LAMSs and 125 received DPPSs. Measured outcomes included clinical success, technical success, adverse events, stent dysfunction, pancreatic pseudocyst recurrence, and need for surgery.Results: Technical success was similar between the LAMS and the DPPS groups (97.5 % vs. 99.2 %; P = 0.32). Clinical success was higher for LAMSs than for DPPSs (96.3 % vs. 87.2 %; P = 0.03). While the need for surgery was similar between the two groups (1.3 % vs. 4.9 %, respectively; P = 0.17), the use of percutaneous drainage was significantly lower in the LAMS group (1.3 % vs. 8.8 %; P = 0.03). At 6-month follow-up, the recurrence rate was similar between the groups (6.7 % vs 18.8 %, respectively; P = 0.12). The rate of adverse events was significantly higher in the DPPS group (7.5 % vs. 17.6 %; P = 0.04). There was no difference in post-procedure mean length of hospital stay (6.3 days [standard deviation 27.9] vs. 3.7 days [5.7]; P = 0.31).Conclusion: When compared to DPPSs, LAMSs are a safe, feasible, and effective modality for the treatment of pancreatic pseudocysts and are associated with a higher rate of clinical success, shorter procedure time, less need for percutaneous interventions, and a lower overall rate of adverse events. [ABSTRACT FROM AUTHOR]

• Fresh state properties including rheology of rubber fiber dosed SCM were studied. • All rubber fiber dosed SCM mixes exhibited shear-thinning behavior. • The inclusion of rubber fibers improved the thixotropy of SCM mixes. • 15% rubber fiber replacement provided optimum flow characteristics for SCM. The improper disposal of waste rubber tires leads to severe environmental and health issues, which can be mitigated through the use of waste tire rubber particles as construction material. In the present study, use of fiber shaped rubber particles has been explored as fine aggregates (up to 25%) in self-compacting mortar (SCM). Fresh state properties of SCM mixes have been studied using conventional and rheological tests. Conventional tests have been used to evaluate air content, fresh density, flow time (using mini V-funnel), and flow spread (using mini-slump). Rheological tests have been used to observe the flow curves (shear stress and viscosity curves), dynamic yield stress, plastic viscosity, shear thinning behaviour and thixotropic behaviour. Particle interaction in fresh state has also been observed using optical microscopy. Results indicate that air content and flow time increase with rubber fiber incorporation whereas the fresh density and flow spread decrease with rubber fiber incorporation in SCM mixes. Addition of rubber fiber exhibited a loss of flow characteristics (increase in dynamic yield stress and plastic viscosity) in SCM mixes. Shear-thinning behaviour was observed for all mortar mixes with the highest intensity of shear-thinning in 15% rubber fiber mortar. Thixotropy was observed to increase with rubber content. As per the acceptance limits defined for conventional tests, up to 15% rubber fiber can be used for the preparation of SCM in the adopted mixes. [ABSTRACT FROM AUTHOR]