Tools to support policy decisions related to treatment strategies and surveillance of Schistosomiasis japonica towards elimination

Background

Appropriate diagnostics to monitor disease trends and assess the effectiveness and impact of interventions are essential for guiding treatment strategies at different thresholds of schistosomiasis transmission and for certifying elimination. Field validation of these assays is urgently needed before they can be adopted to support policy decisions of the national programme for control and elimination of schistosomiasis in P.R. China. We compared the efficacy and utility of different immunoassays in guiding control strategies and monitoring the endemic status of S. japonicum infections towards elimination.

Methodology/Principal Findings

A cross-sectional survey was conducted in seven villages with different transmission intensities settings to assess the performance and utility of three immunoassays, e.g., an indirect hemagglutination assay (IHA_JX), an enzyme linked immunosorbent assay (ELISA_SZ), and a dot immunogold filtration assay (DIGFA_SH). 6,248 individuals aged 6–65 years old who gave consent and supplied their stool and blood samples were included for data analysis. Results showed that ELISA_SZ performed significantly higher sensitivity (95.45%, 95%CI: 92.94–97.97%) than IHA_JX (87.59%, 95%CI: 83.51–91.49%) and DIGFA_SH (79.55%, 95%CI: 74.68–84.41%), especially in subgroups with very low infection intensity. The specificity of ELISA_SZ, IHA_JX, DIGFA_SH in 6–9 year olds with occasional exposure was nearly 90%. DIGFA_SH performed the highest screening efficacy for patients among three assays with overall positive predicative value of 13.07% (95%CI: 11.42–14.72%). We found a positive correlation of antibody positive rate of IHA_JX with results of stool examination in age strata (r = 0.70, P<0.001). Seropositivity of IHA_JX in children aged 6–9 years old showed an excellent correlation with prevalence of schistosome infection in the seven communities (r = 0.77, P<0.05).

Conclusions/Significance

Studies suggest that ELISA_SZ could be used to guide selective chemotherapy in moderate or low endemic regions. IHA_JX could be used to as a surveillance tool and for certifying elimination of schistosomiasis through monitoring children as a sentinel population.     

Advances in systems metabolic engineering of autotrophic carbon oxide-fixing biocatalysts towards a circular economy

High levels of anthropogenic CO₂ emissions are driving the warming of global climate. If this pattern of increasing emissions does not change, it will cause further climate change with severe consequences for the human population. On top of this, the increasing accumulation of solid waste within the linear economy model is threatening global biosustainability. The magnitude of these challenges requires several approaches to capture and utilize waste carbon and establish a circular economy. Microbial gas fermentation presents an exciting opportunity to capture carbon oxides from gaseous and solid waste streams with high feedstock flexibility and selectivity. Here we discuss available microbial systems and review in detail the metabolism of both anaerobic acetogens and aerobic hydrogenotrophs and their ability to utilize C1 waste feedstocks. More specifically, we provide an overview of the systems-level understanding of metabolism, key metabolic pathways, scale-up opportunities and commercial successes, and the most recent technological advances in strain and process engineering. Finally, we also discuss in detail the gaps and opportunities to advance the understanding of these autotrophic biocatalysts for the efficient and economically viable production of bioproducts from recycled carbon.     

Developing Regenerate: A circular economy engagement tool for the assessment of new and existing buildings

The transition toward a circular economy (CE) is key in decarbonizing the built environment. Despite this, knowledge of—and engagement with—CE philosophies remains limited within the construction industry. Discussion with practitioners reveals this to be contributed to by a lack of clarity regarding CE principles, with numerous organizations recommending implementation of differing and sometimes conflicting principles. In addition, a systematic assessment of how building designs consider CE is made difficult by the multiple design areas required to be considered and the large amount of design data required to do so. The absence of a systematic CE assessment causes a lack of comparability across designs, preventing benchmarking of CE practices in building design at present. This paper details the development of Regenerate, a CE engagement tool for the assessment of new and existing buildings, established in an effort to overcome the aforementioned barriers to the adoption of CE within the construction sector. A CE design workflow for the built environment is proposed, comprising four overarching circularity principles (Design for Adaptability; Design for Deconstructability; Circular Material Selection; Resource Efficiency) and contributing design actions. In addition to engaging stakeholders by enabling the assessment of building designs, the tool retrieves key data for further research. Information on completed design actions as well as recycling and waste metrics is collected to facilitate future CE benchmarking. “Bill of materials” data (i.e., material quantities) is also compiled, with this being key in material stock modeling research and embodied carbon benchmarking.     

Model of outcomes of screening mammography: information to support informed choices

Objective To provide easy to use estimates of the benefits and harms of biennial screening mammography for women aged 40, 50, 60, and 70 years.Design Markov process model, with data from BreastScreen Australia, the Australian Institute of Health and Welfare, and the Australian Bureau of Statistics.Main outcome measure Age specific outcomes expressed per 1000 women over 10 years.Results For every 1000 women screened over 10 years, 167-251 (depending on age) receive an abnormal result; 56-64 of these women undergo at least one biopsy, 9-26 have an invasive cancer detected by screening, and 3-6 have ductal carcinoma in situ (DCIS) detected by screening. More breast cancers (both invasive and DCIS) are diagnosed among screened than unscreened women. For example, among 1000 women aged 50 who have five biennial screens, 33 breast cancers are diagnosed: 28 invasive cancers (18 detected at screening and 10 interval cancers) and five DCIS (all detected at screening). By comparison, among 1000 women aged 50 who decline screening, 20 cancers are diagnosed over 10 years. There are about 0.5, 2, 3, and 2 fewer deaths from breast cancer over 10 years per 1000 women aged 40, 50, 60, and 70, respectively, who choose to be screened compared with women who decline screening at times determined by relevant policy.Conclusion Benefits and harms of screening mammography are relatively finely balanced. Quantitative estimates such as these can be used to support individual informed choices about screening.     

When more is more: taking advantage of species diversity to move towards sustainable aquaculture

Human population growth has increased demand for food products, which is expected to double in coming decades. Until recently, this demand has been met by expanding agricultural area and intensifying agrochemical-based monoculture of a few species. However, this development pathway has been criticised due to its negative impacts on the environment and other human activities. Therefore, new production practices are needed to meet human food requirements sustainably in the future. Herein, we assert that polyculture practices can ensure the transition of aquaculture towards sustainable development. We review traditional and recent polyculture practices (ponds, recirculated aquaculture systems, integrated multi-trophic aquaculture, aquaponics, integrated agriculture–aquaculture) to highlight how they improve aquaculture through the coexistence and interactions of species. This overview highlights the importance of species compatibility (i.e. species that can live in the same farming environment without detrimental interactions) and complementarity (i.e. complementary use of available resources and/or commensalism/mutualism) to achieve efficient and ethical aquaculture. Overall, polyculture combines aspects of productivity, environmental protection, resource sharing, and animal welfare. However, several challenges must be addressed to facilitate polyculture development across the world. We developed a four-step conceptual framework for designing innovative polyculture systems. This framework highlights the importance of (i) using prospective approaches to consider which species to combine, (ii) performing integrated assessment of rearing environments to determine in which farming system a particular combination of species is the most relevant, (iii) developing new tools and strategies to facilitate polyculture system management, and (iv) implementing polyculture innovation for relevant stakeholders involved in aquaculture transitions.     

How to monitor environmental pressures of a circular economy: An assessment of indicators

Understanding how a circular economy (CE) can reduce environmental pressures from economic activities is crucial for policy and practice. Science provides a range of indicators to monitor and assess CE activities. However, common CE activities, such as recycling and eco‐design, are contested in terms of their contribution to environmental sustainability. This article assesses whether and to what extent current approaches to assess CE activities sufficiently capture environmental pressures to monitor progress toward environmental sustainability. Based on a material flow perspective, we show that most indicators do not capture environmental pressures related to the CE activities they address. Many focus on a single CE activity or process, which does not necessarily contribute to increased environmental sustainability overall. Based on these results, we suggest complementing CE management indicators with indicators capturing basic environmental pressures related to the respective CE activity. Given the conceptual linkage between CE activities, resource extraction, and waste flows, we suggest that a resource‐based footprint approach accounting for major environmental inputs and outputs is necessary—while not sufficient—to assess the environmental sustainability of CE activities. As footprint approaches can be used across scales, they could aid the challenging process of developing indicators for monitoring progress toward an environmentally sustainable CE at the European, national, and company levels.     

Supporting a transition towards sustainable circular economy: sensitivity analysis for the interpretation of LCA for the recovery of electric and electronic waste

Purpose

The interpretation is a fundamental phase of life cycle assessment (LCA). It ensures the robustness and the reliability of the overall study. Moving towards more circular economy requires that different waste management options are systematically scrutinized to assess the environmental impacts and benefits associated to them. The present work aims at illustrating how a sensitivity analysis could be applied to the impact assessment step supporting the interpretation of a LCA study applied to a waste management system that includes material recovering. The focus is on toxicity-related and resource-related potential impacts as they are considered among the most critical ones, which may affect the way the final benefit from material recovery is evaluated.

Methods

Possible alternatives in terms of impact assessment assumptions and modelling are tested by performing a sensitivity analysis on a case study on electric and electronic waste. For the toxicity-related impact categories, first, a sensitivity analysis is performed using different sets of characterization factors for metals aiming at identifying how they are affecting the final results. Then, an analysis of the relative contribution of long-term emissions in upstream processes is carried out aiming at unveiling critical issues associated to their inclusion or exclusion. For the resource depletion impact category, a sensitivity analysis has been performed, adopting different sets of characterization factors based on existing models for minerals and metals as well as recently proposed sets accounting for critical raw materials.

Results and discussion

The indicator of the ecotoxicity impact category obtained by applying the updated characterization factors is about three times higher than the corresponding obtained by the USEtox model. The long-term emission result is responsible for the major part of all the toxicity impact indicators. Moreover, for the ecotoxicity indicator, excluding the long-term emissions changes the total results from being negative into positive. The sensitivity analysis for the resource depletion impact category shows that all the models applied result in a total avoided impact. A quantitative comparison among all the results is not possible as the different models use different units of measure.

Conclusions

The application of LCA is crucial for assessing avoided impacts and uncovers potential impacts due to recycling. However, contrasting results may stem from the application of different assumptions and models for characterization. A robust interpretation of the results should be based on systematic assessment of the differences highlighted by the sensitivity, as guidance for delving into further analysis of the drivers of impacts and/or to steer ecoinnovation to reduce those impacts.

     

Virtual screening of phytochemicals to novel targets in Haemophilus ducreyi towards the treatment of Chancroid

Conventionally, drugs are discovered by testing chemically synthesized compounds against a battery of in vivo biological screens. Information technology and Omic science enabled us for high throughput screening of compound libraries against biological targets and hits are then tested for efficacy in cells or animals. Chancroid, caused by Haemophilus ducreyi is a public health problem and has been recognized as a cofactor for Human Immunodeficiency Virus (HIV) transmission. It facilitates HIV transmission by providing an accessible portal entry, promoting viral shedding, and recruiting macrophages as well as CD4 cells to the skin. So, there is a requirement to develop an efficient drug to combat Chancroid that can also diminish HIV infection. In-silico screening of potential inhibitors against the target may facilitate in detection of the novel lead compounds for developing an effective chemo preventive strategy against Haemophilus ducreyi. The present study has investigated the effects of approximately 1100 natural compounds that inhibit three vital enzymes viz. Phosphoenolpyruvate phosphotransferase, Acetyl-coenzyme A carboxylase and Fructose 1, 6-bisphosphatase of Haemophilus ducreyi in reference to a commercial drug Rifabutin. Results reveal that the lead compound uses less energy to bind to target. The lead compound parillin has also been predicted as less immunogenic in comparison to Rifabutin. Further, better molecular dynamics, pharmacokinetics, pharmacodynamics and ADME-T properties establish it as an efficient chancroid preventer.     

The free-radical theory of ageing--older, wiser and still alive: modelling positional effects of the primary targets of ROS reveals new support

The continuing viability of the free-radical theory of ageing has been questioned following apparently incompatible recent results. We show by modelling positional effects of the generation and primary targets of reactive oxygen species that many of the apparently negative results are likely to be misleading. We conclude that there is instead a need to look more closely at the mechanisms by which free radicals contribute to age-related dysfunction in living systems. There also needs to be deeper understanding of the dynamics of accumulation and removal of the various kinds of molecular damage, in particular mtDNA mutations. Finally, the expectation that free-radical damage on its own might cause ageing needs to be relinquished in favour of the recognition that the free-radical theory is just one of the multiple mechanisms driving the ageing process.     

Detection of potential enzyme targets by metabolic modelling and optimization: application to a simple enzymopathy

MOTIVATION: A very promising approach in drug discovery involves the integration of available biomedical data through mathematical modelling and data mining. We have developed a method called optimization program for drug discovery (OPDD) that allows new enzyme targets to be identified in enzymopathies through the integration of metabolic models and biomedical data in a mathematical optimization program. The method involves four steps: (i) collection of the necessary information about the metabolic system and disease; (ii) translation of the information into mathematical terms; (iii) computation of the optimization programs prioritizing the solutions that propose the inhibition of a reduced number of enzymes and (iv) application of additional biomedical criteria to select and classify the solutions. Each solution consists of a set of predicted values for metabolites, initial substrates and enzyme activities, which describe a biologically acceptable steady state of the system that shifts the pathologic state towards a healthy state. RESULTS: The OPDD was used to detect target enzymes in an enzymopathy, the human hyperuricemia. An existing S-system model and bibliographic information about the disease were used. The method detected six single-target enzyme solutions involving dietary modification, one of them coinciding with the conventional clinical treatment using allopurinol. The OPDD detected a large number of possible solutions involving two enzyme targets. All except one contained one of the previously detected six enzyme targets. The purpose of this work was not to obtain solutions for direct clinical implementation but to illustrate how increasing levels of biomedical information can be integrated together with mathematical models in drug discovery. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.     

Evaluation and modelling the utility of SCCO2 to support efficient lipase mediated esterification

Supercritical fluids offer environmental advantages over chemical solvents, while providing enhanced separation and chemical selectivity. The use of supercritical fluids for the recovery of products from biomass and the transformation of selected molecules (to add value) was studied. Free fatty acids were bio-catalytically transformed to fatty acid esters using lipase within a supercritical fluid environment. A central composite rotatable design was used to evaluate the influence of operating conditions on the enzymatic esterification process and a response surface equation was optimized to identify the most favourable process conditions for maximum free fatty acid conversion. Based on the model equation the process conditions under which it was predicted a yield of 100% esters could be obtained were: pressure 200 bar, temperature 60 °C, ethanol concentration 2.0 M, enzyme concentration 11 wt.% and time 60 min. Experiments conducted under these conditions gave an ester yield of 94.3% (close to predicted results). The activity per unit mass of biocatalyst was found to be 1585 μmol/min/g_cat. The results support the use of supercritical fluids for process integration.     

Moving from completing system boundaries to more realistic modeling of the economy in life cycle assessment

The International Journal of Life Cycle Assessment - Existing process-based life cycle assessment (LCA) models can be supplemented by input-output (IO) models to correct for the so-called...     

Transforming existing local ecosystems to circular economy ecosystems for plastics: The case of the PlastiCity ecosystem

This paper discusses the transition toward a circular economy ecosystem (CEE) for plastics by assessing and mapping existing ecosystems and coordinating efforts among ecosystem actors. The PlastiCity ecosystem is used as a case study. The study employs ecosystem analysis and mapping to identify the new activities and actors needed to transition toward a CEE. These include local and eco-friendly transportation, plastic recycling knowledge management, and upgrading the existing recycling infrastructure. The findings emphasize the significance of the joint orchestration of ecosystem actors facilitated by an ecosystem coordinator and knowledge team to achieve a CEE. It presents a tangible and feasible approach to achieving a local plastic CEE. The policymakers are encouraged to support collaborative orchestration efforts among ecosystem actors and establish knowledge management practices that facilitate ecosystem transitions.     

Analysis of parameters about useful life extension in 70 tools and methods related to eco-design and circular economy

One of the approaches followed by the circular economy (CE) to achieve sustainability through design is product life extension. Extending the life of products to make them useful for as long as possible is a means to reduce waste production and materials consumption, as well as the related impacts. For designers, conceptualizing products in a way that allows them to be used for longer is a challenge, and assessing how well they extend their lifespan can be helpful when it comes to choosing the best proposal. In this paper, 70 tools and methods related to eco-design and circular economy are studied to determine how many of them consider parameters related to life extension and which can be applied in the early stages of design. The results of the analysis show that most of the existing tools and methods are applicable to developed products, and only a few of them take into account parameters related to extending the useful life. Of the 70 tools and methods, only 14 include some parameter related to life extension and are applicable to concepts. CE toolkit, Eco-design PILOT, CE Designer, Circularity Assessment tool, Circularity Potential Indicator and Circular Design Tools take into consideration eight or more parameters to assess life extension in concepts. This will help designers select the most appropriate and will indicate the need for more complete tools to consider useful life extension in the early stages of design and thus enhance the selection of more sustainable products.     

Modified thalamocortical model: A step towards more understanding of the functional contribution of astrocytes to epilepsy

It is evident that the cortex plays a primary role in seizure generation. At the same time, various experimental results clearly confirm that thalamic neurons are also actively involved in seizure generation and spreading. On the other hand, recent neurophysiologic findings suggest that astrocytes regulate dynamically the synaptic activity in neuronal networks. Therefore, in the present study, the thalamocortical neural population model (TCPM) is modified by embedding into the model the functional role of astrocytes in the regulation of synaptic transmission. Using the modified TCPM (MTCPM) we examined the hypothesis that one of the possible causes of neural hypersynchronization is the dysfunction of astrocytes in the regulatory feedback loop. Then, two MTCPMs are coupled via excitatory synapses and the astrocytes are also coupled together through gap junctions. Utilizing the MTCPM and CMTCPM, the transition from normal to malfunctioned states is analyzed using a dynamical system approach. In this way, the hypothesis is investigated and it is demonstrated that the healthy astrocytes provide feedback control to regulate neural activity. That is, the astrocytes compensate to a large extent variations in the coupling between neural populations and maintain the balance between the excitation and inhibition levels. However, the malfunctioned astrocytes are no longer able to regulate and/or compensate the excessive increase of the inter-population coupling strength. As a consequence, disruption of the signaling function of astrocytes could contribute to the neuronal hyperexcitability and generating epileptiform activity. These results suggest that astrocytes might be one of the potential targets for the treatment of epilepsy.