Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms : revival of an old drug

BACKGROUND: It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. METHODOLOGY: We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. PRINCIPAL FINDINGS: We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. CONCLUSIONSIGNIFICANCE: Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launche

Spatio-temporal log-Gaussian Cox processes on earthquake events

This work presents an application of spatio-temporal log-Gaussian Cox processes for the description of earthquake events. To explain the overall spatial trend, spatial geological information in the study area such as faults and volcanoes are introduced in the model. Moreover, an anisotropic specification of the covariance matrix of the Gaussian process is used to improve the explanation of the phenomenon. We apply and compare different models to explain the seismic events occurred in Alaska over the last decades

Activity of tribendimidine and praziquantel combination therapy against the liver fluke Opisthorchis viverrini in vitro and in vivo

Opisthorchiasis, caused by the liver fluke Opisthorchis viverrini, a food-borne trematode, is an important public health problem; however, only a single drug, praziquantel is available. We investigated tribendimidine-praziquantel combinations against O. viverrini in vitro and in vivo. The IC50 values of 0.16μg/ml and 0.05μg/ml were determined for praziquantel and tribendimidine, respectively, against adult O. viverrini in vitro. When O. viverrini was exposed to both drugs simultaneously (using a drug ratio based on the IC50 (1:3.2)) a synergistic effect was calculated (combination index (CI) at the IC50=0.7). A similar result was observed when drug addition in vitro was spaced by the respective half-lives of the drugs (a CI of 0.78 at the IC50 for tribendimidine followed by praziquantel and a CI of 0.47 at the IC50 for praziquantel followed by tribendimidine). In vivo median-effect dose (ED50) values of 191mg/kg and 147mg/kg were calculated for praziquantel and tribendimidine, respectively. Low to moderate worm burden reductions (38-62%) were observed in O. viverrini infected hamsters when both drugs were administered simultaneously or on subsequent days, pointing to antagonistic effects in vivo. Further studies are necessary to understand the striking differences between the in vitro and in vivo observations using combinations of praziquantel and tribendimidine on O. viverrin

London's King's Cross redevelopment: a compact, resource efficient and 'liveable' global city model for an era of climate emergency?

Cities have long been subject to urban containment policies against urban sprawl. Climate change concerns have recently added to the imperative to densify urban space. Urban compaction is often pursued through the creation of ‘exemplar’ urban developments that superficially implement ‘best practice’ ideas from elsewhere. In this paper, we abandon the notion of ‘best practice’ in favour of context-sensitive ‘good practices’. Taking London’s King’s Cross redevelopment as a case study, this paper draws on qualitative methods to examine the contribution of context and path-dependency, as a product of local and non-local forces, to the emergence of King´s Cross as ‘good practice’

Financial contagion through space-time point processes

We propose to study the dynamics of financial contagion by means of a class of point process models employed in the modeling of seismic contagion. The proposal extends network models, recently introduced to model financial contagion, in a space-time point process perspective. The extension helps to improve the assessment of credit risk of an institution, taking into account contagion spillover effects

Some properties of local weighted second-order statistics for spatio-temporal point processes

Diagnostics of goodness-of-fit in the theory of point processes are often considered through the transformation of data into residuals as a result of a thinning or a rescaling procedure. We alternatively consider here second-order statistics coming from weighted measures. Motivated by Adelfio and Schoenberg (2009) for the temporal and spatial cases, we consider an extension to the spatio-temporal context in addition to focussing on local characteristics. In particular, our proposed method assesses goodness-of-fit of spatio-temporal models by using local weighted secondorder statistics, computed after weighting the contribution of each observed point by the inverse of the conditional intensity function that identifies the process. Weighted second-order statistics directly apply to data without assuming homogeneity nor transforming the data into residuals, eliminating thus the sampling variability due to the use of a transforming procedure. We provide some characterisations and show a number of simulation studies

Life cycle analysis of innovative building materials based on circular coffee ground supply chain

The construction sector is widely recognized as one of the most polluting mainly due to its intensive exploitation of natural resources and large energy consumption to produce traditional building materials. In the last years, alternative building materials have been developed with the aim to reduce the environmental burden of this sector. In particular, the use of geopolymer mortars as alternative cementitious materials is gaining increasing acceptance among scientists. Numerous laboratory studies demonstrate their suitability for construction applications, highlighting the potential environmental benefits that can be obtained from their large-scale production. This study aims to perform a preliminary evaluation of the environmental performance of a geopolymer mortar, whose production includes the reuse of a food waste: Spent Coffee Ground (SCG). By using the Life Cycle Assessment (LCA) approach, an environmental comparison with a traditional production of cement mortar was carried out on the basis of the Global Warming Potential (GWP) indicator

Economic and Environmental Assessment of Biomass Power Plants in Southern Italy

In 2019, Europe adopted the New Green Deal as a strategic plan to become a competitive, resource-efficient, and driven economy by reducing its gas emissions and carbon footprint. Due the COVID-19 pandemic, this strategic plan was recently updated to expedite the green transition of European industries. Therefore, the present paper deals with the problem of deciding an appropriate size for a biomass plant that directly produces electric energy by means of two different conversion processes: combustion and gasification. After an initial estimation of the energy potential in western Sicily, GIS data of biomass growth were used to identify the appropriate size for the power plants under investigation. The economic feasibility of biomass utilization was evaluated over a capacity range of 10 to 30 MW, considering total capital investments, revenues from energy sales, and total operating costs. Moreover, the effect of variations on incentive prices was analyzed by means of a sensitivity analysis. Comparing the different plant solutions considered, the environmental sustainability was also analyzed using the life cycle assessment (LCA) approach. The results showed that the combustion solution had a higher profitability and a lower environmental impact for each plant size. The obtained results also demonstrated that providing power from residual biomass in small agricultural communities would significantly reduce their environmental impacts while improving the economic feasibility of their waste management practices

Data Integration for Open Data on the Web

In this lecture we will discuss and introduce challenges of integrating openly available Web data and how to solve them. Firstly, while we will address this topic from the viewpoint of Semantic Web research, not all data is readily available as RDF or Linked Data, so we will give an introduction to different data formats prevalent on the Web, namely, standard formats for publishing and exchanging tabular, tree-shaped, and graph data. Secondly, not all Open Data is really completely open, so we will discuss and address issues around licences, terms of usage associated with Open Data, as well as documentation of data provenance. Thirdly, we will discuss issues connected with (meta-)data quality issues associated with Open Data on the Web and how Semantic Web techniques and vocabularies can be used to describe and remedy them. Fourth, we will address issues about searchability and integration of Open Data and discuss in how far semantic search can help to overcome these. We close with briefly summarizing further issues not covered explicitly herein, such as multi-linguality, temporal aspects (archiving, evolution, temporal querying), as well as how/whether OWL and RDFS reasoning on top of integrated open data could be help