Efficient Numerical Schemes for Computing Cardiac Electrical Activation over Realistic Purkinje Networks: Method and Verification

We present a numerical solver for the fast conduction system in the heart using both a CPU and a hybrid CPU/GPU implementation. To verify both implementations, we construct analytical solutions and show that the L2-error is similar in both implementations and decreases linearly with the spatial step size. Finally, we test the performance of the implementations with networks of varying complexity, where the hybrid implementation is, on average, 5.8 times faster

Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

Constructing a climate change logic: An institutional perspective on the "tragedy of the commons"

Despite increasing interest in transnational fields, transnational commons have received little attention. In contrast to economic models of commons, which argue that commons occur naturally and are prone to collective inaction and tragedy, we introduce a social constructionist account of commons. Specifically, we show that actor-level frame changes can eventually lead to the emergence of an overarching, hybrid "commons logic" at the field level. These frame shifts enable actors with different logics to reach a working consensus and avoid "tragedies of the commons." Using a longitudinal analysis of key actors' logics and frames, we tracked the evolution of the global climate change field over 40 years. We bracketed time periods demarcated by key field-configuring events, documented the different frame shifts in each time period, and identified five mechanisms (collective theorizing, issue linkage, active learning, legitimacy seeking, and catalytic amplification) that underpin how and why actors changed their frames at various points in time-enabling them to move toward greater consensus around a transnational commons logic. In conclusion, the emergence of a commons logic in a transnational field is a nonlinear process and involves satisfying three conditions: (1) key actors view their fates as being interconnected with respect to a problem issue, (2) these actors perceive their own behavior as contributing to the problem, and (3) they take collective action to address the problem. Our findings provide insights for multinational companies, nation-states, nongovernmental organizations, and other stakeholders in both conventional and unconventional commons

Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production.

Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME. Together, our data indicate that priming of microglial ROS production involves reduction of intracellular glutathione levels, upregulation of NADPH oxidase subunit NOX2 and increases in nitric oxide production, and suggest that these simultaneously occurring processes result in enhanced production of neurotoxic peroxynitrite. Furthermore, IFNγ-induced priming of microglial ROS production was reduced upon blockade of Kir2.1 inward rectifier K+ channels with ML133. Inhibitory effects of ML133 on microglial priming were mediated via regulation of intracellular glutathione levels and nitric oxide production. These data suggest that microglial Kir2.1 channels may represent novel therapeutic targets to inhibit excessive ROS production by primed microglia in brain pathology

Development of sentinel node localization and ROLL in breast cancer in Europe

The concept of a precise region in which to find the lymph nodes that drain the lymph directly from the primary tumor site can be traced back to a century ago to the observations of Jamieson and Dobson who described how cancer cells spread from cancer of the stomach in a single lymph node, which they called the â\u80\u9cprimary glandâ\u80\u9d. However, Cabanas was the first in 1977 to realize the importance of this concept in clinical studies following lymphography performed in patients with penile cancer. Thanks to Mortonâ\u80\u99s studies on melanoma in 1992, we began to understand the potential impact of the sentinel lymph node (SN) on the surgical treatment of this type of cancer. The use of a vital dye (blue dye) administered subdermally in the region surrounding the melanoma lesion led to the identification of the sentinel node, and the vital dye technique was subsequently applied to other types of solid tumors, e.g. breast, vulva. However, difficulties in using this technique in anatomical regions with deep lymphatic vessels, e.g. axilla, led to the development of lymphoscintigraphy, started by Alex and Krag in 1993 on melanoma and breast cancer and optimized by our group at European Institute of Oncology (IEO) in Milan in 1996. Today, lymphoscintigraphy is still considered as the most reliable method for the detection of the SN. In 1996, a new method for the localization of non-palpable breast lesion called radioguided occult lesion localization (ROLL) was also developed at IEO. Retrospective and prospective studies have since shown that the ROLL procedure permits the easy and accurate surgical removal of non-palpable breast lesions, overcoming the limitations of previous techniques such as the wire-guided localization. The purpose of this paper is to describe the evolution of SN biopsy and radioguided surgery in the management of breast cancer. We also include a review of the literature on the clinical scenarios in which SN biopsy in breast cancer is currently used, with particular reference to controversies and future prospects

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research

Endocrine disruptors and obesity

The purpose of this review is to summarise current evidence that some environmental chemicals may be able to interfere in endocrine regulation of energy metabolism and adipose tissue structure. Recent findings demonstrate that such endocrine disrupting chemicals, termed “obesogens”, can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and ingredients in personal care products. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period. In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing retention of other lipophilic pollutant chemicals with an even broader range of adverse actions. This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer

Intelligent Resource Management for eMBB and URLLC in 5G and beyond Wireless Networks

Copyright © 2023 The Authors. In the era of 5G and beyond wireless networks, the simultaneous support of enhanced Mobile Broadband (eMBB) and Ultra-Reliable Low Latency Communications (URLLC) poses significant challenges in managing radio resources efficiently. By leveraging the puncturing technique, we propose an intelligent resource management framework for meeting the strict latency and reliability requirement of URLLC services and the high data rate for eMBB services. In particular, a semi-supervised learning and deep reinforcement learning (DRL) based architecture is proposed to manage the resources intelligently. We decompose the optimization problem into two subproblems: 1) resource block allocation (RBA) strategy for eMBB slice, and 2) URLLC scheduling. Through extensive simulations and performance evaluations, we demonstrate the effectiveness of the proposed technique in optimizing resource utilization, minimizing latency for URLLC users, and maximizing the throughput for eMBB services. Simulation findings demonstrate that the proposed methodology can ensure the URLLC reliability requirements while maintaining higher average sum rate for eMBB and higher convergence rate. The proposed framework paves the way for the efficient coexistence of diverse services, enabling wireless network operators to optimize resource allocation, improve user experience, and meet the specific requirements of eMBB and URLLC applications.10.13039/501100000266-Engineering and Physical Sciences Research Council (EPSRC) U.K.-India Future Networks Initiative (Grant Number: ref-EP/W016524/1) 10.13039/501100000736-University of East Anglia in U.K

Maintenance of cross-sector partnerships: the role of frames in sustained collaboration

We examine the framing mechanisms used to maintain a cross-sector partnership (XSP) that was created to address a complex long-term social issue. We study the first eight years of existence of an XSP that aims to create a market for recycled phosphorus, a nutrient that is critical to crop growth but whose natural reserves have dwindled significantly. Drawing on 27 interviews and over 3,000 internal documents, we study the evolution of different frames used by diverse actors in an XSP. We demonstrate the role of framing in helping actors to avoid some of the common pitfalls for an XSP, such as debilitating conflict, and in creating sufficient common ground to sustain collaboration. As opposed to a commonly held assumption in the XSP literature, we find that collaboration in a partnership does not have to result in a unanimous agreement around a single or convergent frame regarding a contentious issue. Rather, successful collaboration between diverse partners can also be achieved by maintaining a productive tension between different frames through ‘optimal’ frame plurality – not excessive frame variety that may prevent agreements from emerging, but the retention of a select few frames and the deletion of others towards achieving a narrowing frame bandwidth. One managerial implication is that resources need not be focussed on reaching a unanimous agreement among all partners on a single mega-frame vis-à-vis a contentious issue, but can instead be used to kindle a sense of unity in diversity that allows sufficient common ground to emerge, despite the variety of actors and their positions