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

Functional Principal components direction to cluster earthquake waveforms

Looking for curves similarity could be a complex issue characterized by subjective choices related to continuous transformations of observed discrete data (Chiodi, 1989). In this paper we combine the aim of finding clusters from a set of individual curves to the functional nature of data, applying a variant of a k-means algorithm based on the principal component rotation of data. We apply a classical clustering method to rotated data, according to the direction of maximum variance. A k-means clustering algorithm based on PCA rotation of data is proposed, as an alternative to methods that require previous interpolation of data based on splines or linear fitting (Garc´ıa- Escudero and Gordaliza (2005), Tarpey (2007), Sangalli et al. (2008)

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

Development of a Vessel Scheduling Optimization Model to improve Maritime Transport sustainability

The social and economic development of the islands is generally dependent on the interconnection level with the mainland obtained through maritime transport services. When connecting many islands, the route planning is essential and typically a variety of constraints must be considered. Various optimization methods have been established to improve cost-efficiency but today environmental concerns, like the reduction of CO2 emissions, have become mandatory. This paper proposes a vessel scheduling optimization model able to simultaneously consider compulsory and optional tasks and vehicle-dependent profits. The algorithm was applied to seven islands of the Tyrrhenian Sea located in front of Sicily, named “Aeolian Islands”. Considering the regional requirements in terms of minimum number of routes and maximum fare prices for each season, this research compared the optimal vessels option obtained maximizing the profit with the one obtained minimizing the emissions. In particular, we have conducted three different analyses, in the first one we have considered only the mandatory routes while the second one was carried out identifying a series of potentially attractive additional activities based on historical demand data provided by the company that currently manages the service. Finally, the third analysis addresses a scenario where older fuel-powered vessels were replaced with hybrid electric ones

Geomorphic and Climatic Controls on Water Temperature and Streambed Scour, Copper River Delta, Alaska : Implications for Understanding Climate Change Impacts to the Pacific Salmon Egg Incubation Environment

Pacific salmon (Oncorhynchus spp.) face numerous challenges associated with climate change. Most research has emphasized the potential effects of elevated summer water temperatures; however, climatic changes are also projected to significantly alter incubation and rearing habitats during the late autumn, winter, and spring months ("the incubation period"). Along the southern coast of Alaska, projected climatic changes include increases in the frequency of above freezing winter temperatures and reductions in low elevation snowpack. These changes are expected to impact the hydrology of salmon streams by increasing both water temperatures and the magnitude and frequency of winter floods. Projected increases in water temperature may accelerate embryo development, impacting juvenile viability. More powerful and more frequent winter floods could reduce the survival of salmon eggs by increasing streambed scour. Here, I investigate climatic and geomorphic controls of water temperature and potential scour depth at salmon spawning and rearing sites on the Copper River Delta, a large coastal foreland in Southcentral Alaska. In chapter 2, I utilized surface water temperature data collected at 18 sites to test the abilities of regression models to project year-round water temperature metrics based on catchment characteristics (elevation, slope, area, percent lake area) and air-water temperature correlations. Considerable variability in water temperature was observed on spatial and temporal scales. Both temperature maxima and the frequency of freezing conditions were positively correlated with percent lake area and negatively correlated with catchment elevation and slope. Sites with upwelling groundwater and sites with high-relief, high elevation catchments exhibited lower thermal sensitivity and water temperatures are anticipated to be less impacted by projected climatic changes. In chapter 3, I utilized surface and streambed water temperature data collected at 8 spawning sites to compare water temperatures during incubation periods under climatological mean ("severe winter") and anomalously warm ("mild winter") conditions. I also collected stream stage and channel geometry data at a subset of 3 sites and calculated streambed scour at bankfull discharge. The magnitude and seasonality of accumulated thermal units (°C/day) (ATU) within spawning gravels varied significantly between severe and mild winters at shallow flowpath sites, but not at upwelling groundwater sites. When seasonal snow and ice was absent, increases in spring ATU at shallow flowpath sites were particularly significant. Modelled mean scour depths varied from 3 to 72 cm, suggesting the impacts of scour on egg mortality will be variable across the landscape. I conclude that the impacts of projected climatic changes are likely to vary in magnitude across the Copper River Delta, even at small spatial scales, due to heterogeneity in climatic and geomorphic controls

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

Feature detection in point processes on linear networks using nearest neighbour volumes

We consider the feature detection problem in the presence of clutter in point processes on linear networks. We extend the classification method developed in previous studies to this more complex geometric context, where the classical properties of a point process change and data visualization are not intuitive. We use the K-th nearest neighbour volumes distribution in linear networks for this approach. As a result, our method is suitable for analysing point patterns consisting of features and clutter as two superimposed Poisson processes on the same linear network. To illustrate the method, we present simulations and examples of road traffic accidents that resulted in injuries or deaths in two cities in Colombia

Cardiovascular Implantable Electronic Device Infection and New Insights About Correlation Between Pro-inflammatory Markers and Heart Failure: A Systematic Literature Review and Meta-Analysis

Introduction: Surgical approaches to treat patients with abnormal pro-inflammatory parameters remain controversial, and the debate on the correlation between hematological parameter alteration in cardiac implantable electronic device (CIED) infection and the increase in mortality continues. Methods: We performed a systematic review using the PubMed, Scopus, and Cochrane Library databases. Twenty-two articles from May 2007 to April 2020 were selected and divided according to the following topics: prevalence of microbes in patients with CIED infection; characteristics of patients with CIED infection; comparison between patients who underwent and did not undergo replantation after device extraction; and correlation between alteration of hematological parameters and poor prognosis analysis. Results: Epidemiological analysis confirmed high prevalence of male sex, staphylococcal infection, and coagulase-negative staphylococci (CoNS). The most common comorbidity was heart failure. Complete removal of CIED and antimicrobial therapy combination are the gold standard. CIED replacement was associated with higher survival. High preoperative white blood cell count and C-reactive protein levels increased the risk of right ventricular failure (RVF) development. Increased red blood cell distribution width (RDW) value or decreased platelet count was correlated with poor prognosis. No correlation was noted between preoperative leukocytosis and CIED infection

The Multidisciplinary Approach for the Diagnosis of Laryngohyoid Lesions: a Systematic Literature Review and Meta-Analysis

Background: The diagnosis of neck lesions remains a medico-legal diagnostic challenge because of the complexity of the anatomical relationship of the neck's organs and their anthropometric morphological variability. We compared the multidisciplinary approach using autopsy and postmortem computed tomography (PMCT), postmortem fine preparation (PMFP), postmortem micro-computed tomography (micro-CT), and postmortem magnetic resonance (PMMR) with the performance of a single diagnostic method among them evaluating the significance of different results. The multidisciplinary approach significantly reduced the number of unidentified neck lesions. The analysis demonstrates the need to better define the scan protocols and compose forensic guidelines for radiological application. The results of this study point out the need to compare the different diagnostic approaches in deceased subjects to better define the radiological scan protocol based on a multidisciplinary approach, including autopsy and radiological methods and the radiological scan protocols. Methods: We performed a systematic electronic search of retrospective scientific articles in PubMed, the Scopus database, and the Cochrane Library. The following combinations of words were used: "hyoid fracture"; "comparison between PMCT AND autopsy"; "hyoid fracture PMCT AND autopsy"; "hyoid bone fracture AND forensic imaging"; "hyoid fracture AND PMCT"; "neck fracture PMCT AND autopsy"; "laryngohyoid lesions"; "postmortem CT AND autopsy in strangulation"; "postmortem AND strangulation Signs "; "strangulation virtopsy"; and "strangulation AND MRI". We selected 16 articles that were published between March 2003 and June 2020. We conducted a meta-analysis with R software to evaluate the rates. We obtained related confidence intervals and a forest plot. Results: Thyroid cartilage damages were significantly more common than hyoid bone fractures (61.7% vs 42.2%) in a sample of 128 subjects. The synergic uses of autopsy/PMCT, autopsy/PMFP, autopsy/microCT, and autopsy/PMMR revealed significantly higher rates than a single investigation. We analyzed the PMCT scan data. The scan parameters evaluated were as follows: row, scan sample, reconstruction, kernel, slice thickness, kVp, and mAs. A lack of uniformity in the application of the protocol was observed. Conclusion: Further studies are needed to better define the radiological scan protocols and to draw guidelines to identify the appropriate radiological methods in relation to the specific case