Anisotropic Continuum-Molecular Models: A Unified Framework Based on Pair Potentials for Elasticity, Fracture and Diffusion-Type Problems

This paper presents a unified framework for continuum-molecular modeling of anisotropic elasticity, fracture and diffusion-based problems within a generalized two-dimensional peridynamic theory. A variational procedure is proposed to derive the governing equations of the model, that postulates oriented material points interacting through pair potentials from which pairwise generalized actions are computed as energy conjugates to properly defined pairwise measures of primary field variables. While mass is considered as continuous function of volume, we define constitutive laws for long-range interactions such that the overall anisotropic behavior of the material is the result of the assigned elastic, conductive and failure micro-interaction properties. The non-central force assumption in elasticity, together with the definition of specific orientation-dependent micromoduli functions respecting material symmetries, allow to obtain a fully anisotropic non-local continuum using a purely pairwise description of deformation and constitutive properties. A general and consistent micro-macro moduli correspondence principle is also established, based on the formal analogy with the classic elastic and conductivity tensors. The main concepts presented in this work can be used for further developments of anisotropic continuum-molecular formulations to include other mechanical behaviors and coupled phenomena involving different physics

The Economic Valuation of Ecosystem Services of Biodiversity Components in Protected Areas: A Review for a Framework of Analysis for the Gargano National Park

Protected areas play an important role in the conservation and protection of biodiversity of particular territories, especially of ecosystems that provide resources for living organisms, including human beings. Different studies highlight the importance of biodiversity and its associated benefits in terms of ecosystem services of protected areas. The economic assessment of ecosystem services and biodiversity becomes a viable solution to help the policy maker to make decisions on the environmental preservation of these areas according to the Agenda 2030 for Sustainable Development. Nonetheless, very few studies provide an economic evaluation of the benefits of protected areas. To advance the current debate on the economic evaluation of the benefits provided by protected areas, the present paper purposes an integrated approach. It presents an overview of main ecosystem services’ mapping techniques currently available to researchers and policy makers and offers a systematic review carried out for the period 2015–2020 at an international level. The main findings are particularly attractive for the Gargano National Park (GNP) in the south of Italy, which is recognised as being a biodiversity hot spot at global level. The current study provides useful guidance for the assessment of trade-offs, the support to policy makers, and the provision of efficient allocation of public resources for protected area

Disseminating the knowledge on the complex interactions between humans and volcanoes: the geological section of the Villa Arbusto archaeological museum at Lacco Ameno (Ischia, Naples - Italy)

A room in the Archaeological Museum of Villa Arbusto (Lacco Ameno, Ischia) was set up to house rocks and fossils collected by the renowned archaeologist Giorgio Buchner during his excavation activity on the Island of Ischia. The collection is witness to a long multidisciplinary research activity that saw archaeological studies at the center of volcanological, pedological and palaeoenvironmental researches, aimed at reconstructing the archaeological contexts in the complex geological dynamics of the island. In fact, during the different phases of colonization recorded on the island, the Ischia volcanoes were very active and produced explosive and effusive eruptions, accompanied by a strong geological dynamics that included earthquakes, landslides (even gigantic ones), rapid ground uplift and strong hydrothermal activity. In the room, the samples on display "tell" the evolution of the island and its dynamics in four windows and a chest of drawers, where there is an exposition of the products of the various eruptions, from the oldest to the most recent, sedimentary rocks and the collection of macro and microfossils found in marine sediments, displaced at variable altitudes by the rapid volcano-tectonic deformations that characterize the island. A series of panels and monitors accompany the visitor along a path that, starting from the geological evolution of the island, passes through the relationship between humans and the volcano, the main volcanic phenomena and the reconstruction of an archaeological excavation of exceptional value, where it is possible to see the strong interaction between primary and secondary volcanic phenomena and a human settlement of the first Greek colony in the west: Pithecusae. The exhibition was designed with the purpose of educating the visitors and the local population about the natural history of the island and its volcanoes, and their impact on the human life through time

EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness

Neuroblastoma (NB) is the most commonly diagnosed extracranial solid tumor in children, accounting for 15% of all childhood cancer deaths. Although the 5-year survival rate of patients with a high-risk disease has increased in recent decades, NB remains a challenge in pediatric oncology, and the identification of novel potential therapeutic targets and agents is an urgent clinical need. The RNA-binding protein LIN28B has been identified as an oncogene in NB and is associated with a poor prognosis. Given that LIN28B acts by negatively regulating the biogenesis of the tumor suppressor let-7 miRNAs, we reasoned that selective interference with the LIN28B/let-7 miRNA interaction would increase let-7 miRNA levels, ultimately leading to reduced NB aggressiveness. Here, we selected (−)-epigallocatechin 3-gallate (EGCG) out of 4959 molecules screened as the molecule with the best inhibitory activity on LIN28B/let-7 miRNA interaction and showed that treatment with PLC/PLGA-PEG nanoparticles containing EGCG (EGCG-NPs) led to an increase in mature let-7 miRNAs and a consequent inhibition of NB cell growth. In addition, EGCG-NP pretreatment reduced the tumorigenic potential of NB cells in vivo. These experiments suggest that the LIN28B/let-7 miRNA axis is a good therapeutic target in NB and that EGCG, which can interfere with this interaction, deserves further preclinical evaluation

Identification of a miRNA-based non-invasive predictive biomarker of response to target therapy in BRAF-mutant melanoma

Rationale: Metastatic melanoma is the most aggressive and dangerous form of skin cancer. The introduction of immunotherapy with Immune checkpoint Inhibitors (ICI) and of targeted therapy with BRAF and MEK inhibitors for BRAF mutated melanoma, has greatly improved the clinical outcome of these patients. Nevertheless, response to therapy remains highly variable and the development of drug resistance continues to be a daunting challenge. Within this context there is a need to develop diagnostic tools capable of predicting response or resistance to therapy in order to select the best therapeutic approach. Over the years, accumulating evidence brought to light the role of microRNAs (miRNAs) as disease biomarkers. Methods: In particular, the detection of miRNAs in whole blood or specific blood components such as serum or plasma, allows these molecules to be good candidates for diagnosis, prognosis and for monitoring response to anticancer therapy. In this paper, we evaluated circulating basal levels of 6 previously identified miRNAs in serum samples of 70 BRAF-mutant melanoma patients before starting targeted therapy. Results: Results show that the circulating levels of the oncosuppressor miR-579-3p and of the oncomiR miR-4488 are able to predict progression free survival (PFS) but not overall survival (OS). Most importantly, we observed that the best predictor of disease outcome is represented by the ratio of circulating miR-4488 vs. miR-579-3p (miRatio). Finally, the combination of the Lactate dehydrogenase (LDH) blood levels with the two circulating miRNAs alone or together did not produce any improvement in predicting PFS indicating that miR-579-3p and miR-4488 are independent predictors of PFS as compared to LDH. Conclusions: All together these data underscored the relevance of circulating miRNAs as suitable tools to predict therapy response in melanoma and maybe further developed as companion diagnostics in the clinic

Disentangling the Possible Drivers of Indri indri Microbiome: A Threatened Lemur Species of Madagascar

Research on the gut microbiome may help with increasing our understanding of primate health with species’ ecology, evolution, and behavior. In particular, microbiome-related information has the potential to clarify ecology issues, providing knowledge in support of wild primates conservation and their associated habitats. Indri (Indri indri) is the largest extant living lemur of Madagascar. This species is classified as “critically endangered” by the IUCN Red List of Threatened Species, representing one of the world’s 25 most endangered primates. Indris diet is mainly folivorous, but these primates frequently and voluntarily engage in geophagy. Indris have never been successfully bred under human care, suggesting that some behavioral and/or ecological factors are still not considered from the ex situ conservation protocols. Here, we explored gut microbiome composition of 18 indris belonging to 5 different family groups. The most represented phyla were Proteobacteria 40.1 ± 9.5%, Bacteroidetes 28.7 ± 2.8%, Synergistetes 16.7 ± 4.5%, and Firmicutes 11.1 ± 1.9%. Further, our results revealed that bacterial alpha and beta diversity were influenced by indri family group and sex. In addition, we investigated the chemical composition of geophagic soil to explore the possible ecological value of soil as a nutrient supply. The quite acidic pH and high levels of secondary oxide-hydroxides of the soils could play a role in the folivorous diet’s gut detoxification activity. In addition, the high contents of iron and manganese found the soils could act as micronutrients in the indris’ diet. Nevertheless, the concentration of a few elements (i.e., calcium, sulfur, boron, nickel, sodium, and chromium) was higher in non-geophagic than in geophagic soils. In conclusion, the data presented herein provide a baseline for outlining some possible drivers responsible for the gut microbiome diversity in indris, thus laying the foundations for developing further strategies involved in indris’ conservation

Risk of Getting COVID-19 in People With Multiple Sclerosis

Background and Objectives Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). Methods Acase-control (1:2) studywas set up. Cases included PwMSwith a confirmed diagnosis ofCOVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score–matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administeredDMT, previousDMTsequences, or the place where the last treatment was administered. Results A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02)with a higher risk of contractingCOVID-19. Patients receiving natalizumab as last DMT(OR[95%CI]: 2.38 [1.66–3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16–2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34–2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. Discussion This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. Classification of Evidence This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective

Progression independent of relapse activity in relapsing multiple sclerosis: impact and relationship with secondary progression

Objectives: We investigated the occurrence and relative contribution of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) to confirmed disability accrual (CDA) and transition to secondary progression (SP) in relapsing multiple sclerosis (MS). Methods: Relapsing-onset MS patients with follow-up > / = 5 years (16,130) were extracted from the Italian MS Registry. CDA was a 6-month confirmed increase in Expanded Disability Status Scale (EDSS) score. Sustained disability accumulation (SDA) was a CDA with no EDSS improvement in all subsequent visits. Predictors of PIRA and RAW and the association between final EDSS score and type of CDA were assessed using logistic multivariable regression and multivariable ordinal regression models, respectively. Results: Over 11.8 ± 5.4 years, 16,731 CDA events occurred in 8998 (55.8%) patients. PIRA (12,175) accounted for 72.3% of CDA. SDA occurred in 8912 (73.2%) PIRA and 2583 (56.7%) RAW (p < 0.001). 4453 (27.6%) patients transitioned to SPMS, 4010 (73.2%) out of 5476 patients with sustained PIRA and 443 (24.8%) out of 1790 patients with non-sustained PIRA. In the multivariable ordinal regression analysis, higher final EDSS score was associated with PIRA (estimated coefficient 0.349, 95% CI 0.120-0.577, p = 0.003). Discussion: In this real-world relapsing-onset MS cohort, PIRA was the main driver of disability accumulation and was associated with higher disability in the long term. Sustained PIRA was linked to transition to SP and could represent a more accurate PIRA definition and a criterion to mark the putative onset of the progressive phase

Sheridan School of Architectural Technology Volume 2 [S2017]

Welcome to Sheridan’s School of Architectural Technician/Technology printed portfolio volume 2. A combination of student work as well as faculty research has once again been been amalgamated into a print and digital portfolio showing the academic excellence of our program. Student work in the book is largely from the course CADD 39788 Architectural Computer Visualisation with a few projects from other courses making guest appearances. Our faculty research section near the back of the book offers insights into the professional interests and engagements of Sheridan professors.https://source.sheridancollege.ca/fast_books/1002/thumbnail.jp

The Time to Offer Treatments for COVID-19

Introduction: COVID-19 has several overlapping phases. Treatment has focused on the late stage of the disease in hospital. Yet, the continuation of the pandemic is by propagation of the disease in outpatients. The current public health strategy relies solely on vaccines to prevent disease. Areas Covered: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results with subject numbers of 100 or more on, and used a targeted search to find announcements of unpublished trial results. As of 2/15/2021, we found 111 publications reporting findings in human studies on 14 classes of agents, and on 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care, the rest all in hospitalized patients. Remdesivir and convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but the supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries Expert Opinion: Worldwide vaccination is now underway. Vaccines and antibodies are highly antigen specific and new variants are appearing. There is a need for treatment of outpatients who contract the disease, in addition to mass immunization. We call on public health authorities to authorize treatments with known low risk and potential benefit for use in parallel with mass immunization