A GRASP-based heuristic for allocating the roadside infrastructure maximizing the number of distinct vehicles experiencing contact opportunities

In this work the allocation of Roadside Units (RSUs) in a V2I network is modeled as a Maximum Coverage Problem. The main objective is to maximize the number of distinct vehicles contacting the infrastructure. Two different approaches are presented to solve the problem. The first one is an ILP model that can found optimal solutions or give sharp upper and lower bounds for the problem. The second one is a GRASP-based heuristic that can found close-to-optimal solutions. The GRASP-based heuristic is compared with a previous work achieving better results. Furthermore, a new metric to measure the efficiency of a Deployment strategy is presented

Radiological Reports: A Comparison between the Transmission Efficiency of Information in Free Text and in Structured Reports

INTRODUCTION: This work proposes to improve the transmission of information between requiring physicians and radiologists. OBJECTIVES: Evaluate the implementation of a structured report (SR) in a university hospital. METHODS: A model of a structured report for thyroid sonography was developed according to information gathered from radiologists and endocrinologists working in this field. The report was based on a web platform and installed as a part of a Radiological Information System (RIS) and a Hospital Information System (HIS). The time for the report generation under the two forms was evaluated over a four-month period, two months for each method. After this period, radiologists and requiring physicians were questioned about the two methods of reporting. RESULTS: For free text, 98 sonograms were reported to have thyroids with nodules in an average time of 8.71 (+/-4.11) minutes, and 59 sonograms of thyroids without nodules were reported in an average time of 4.54 (+/- 3.97) minutes. For SR, 73 sonograms in an average time of 6.08 (+/-3.8) minutes for thyroids with nodules and 3.67 (+/-2.51) minutes for thyroids without nodules. Most of the radiologists (76.2%) preferred the SR, as originally created or with suggested changes. Among endocrinologists, 80% preferred the SR. DISCUSSION: From the requiring physicians' perspective, the SR enabled standardization and improved information transmission. This information is valuable because physicians need reports prepared by radiologists. CONCLUSIONS: The implementation of a SR in a university hospital, under an RIS/HIS system, was viable. Radiologists and endocrinologists preferred the SR when compared to free text, and both agreed that the former improved the transmission of information

QoSatAr: a cross-layer architecture for E2E QoS provisioning over DVB-S2 broadband satellite systems

This article presents QoSatAr, a cross-layer architecture developed to provide end-to-end quality of service (QoS) guarantees for Internet protocol (IP) traffic over the Digital Video Broadcasting-Second generation (DVB-S2) satellite systems. The architecture design is based on a cross-layer optimization between the physical layer and the network layer to provide QoS provisioning based on the bandwidth availability present in the DVB-S2 satellite channel. Our design is developed at the satellite-independent layers, being in compliance with the ETSI-BSM-QoS standards. The architecture is set up inside the gateway, it includes a Re-Queuing Mechanism (RQM) to enhance the goodput of the EF and AF traffic classes and an adaptive IP scheduler to guarantee the high-priority traffic classes taking into account the channel conditions affected by rain events. One of the most important aspect of the architecture design is that QoSatAr is able to guarantee the QoS requirements for specific traffic flows considering a single parameter: the bandwidth availability which is set at the physical layer (considering adaptive code and modulation adaptation) and sent to the network layer by means of a cross-layer optimization. The architecture has been evaluated using the NS-2 simulator. In this article, we present evaluation metrics, extensive simulations results and conclusions about the performance of the proposed QoSatAr when it is evaluated over a DVB-S2 satellite scenario. The key results show that the implementation of this architecture enables to keep control of the satellite system load while guaranteeing the QoS levels for the high-priority traffic classes even when bandwidth variations due to rain events are experienced. Moreover, using the RQM mechanism the user’s quality of experience is improved while keeping lower delay and jitter values for the high-priority traffic classes. In particular, the AF goodput is enhanced around 33% over the drop tail scheme (on average)

On the bioactivity of Echinacea purpurea extracts to modulate the production of inflammatory mediators

Inflammatory diseases are the focus of several clinical studies, due to limitations and serious side effects of available therapies. Plant-based drugs (e.g., salicylic acid, morphine) have become landmarks in the pharmaceutical field. Therefore, we investigated the immunomodulatory effects of flowers, leaves, and roots from Echinacea purpurea. Ethanolic (EE) and dichloromethanolic extracts (DE) were obtained using the Accelerated Solvent Extractor and aqueous extracts (AE) were prepared under stirring. Their chemical fingerprint was evaluated by liquid chromatography–high resolution mass spectrometry (LC-HRMS). The pro- and anti-inflammatory effects, as well as the reduction in intracellular reactive oxygen and nitrogen species (ROS/RNS), of the different extracts were evaluated using non-stimulated and lipopolysaccharide-stimulated macrophages. Interestingly, AE were able to stimulate macrophages to produce pro-inflammatory cytokines (tumor necrosis factor -TNF-α, interleukin -IL-1β, and IL-6), and to generate ROS/RNS. Conversely, under an inflammatory scenario, all extracts reduced the amount of pro-inflammatory mediators. DE, alkylamides-enriched extracts, showed the strongest anti-inflammatory activity. Moreover, E. purpurea extracts demonstrated generally a more robust anti-inflammatory activity than clinically used anti-inflammatory drugs (dexamethasone, diclofenac, salicylic acid, and celecoxib). Therefore, E. purpurea extracts may be used to develop new effective therapeutic formulations for disorders in which the immune system is either overactive or impaired.This research was funded by the Fundação para a Ciência e a Tecnologia (FCT) to the PhD grant of SFV (PD/BD/135246/2017 and COVID/BD/152012/2021) and the projects PATH (PD/00169/2013), FROnTHERA (NORTE-01-0145-FEDER-000023), Cells4_IDs (PTDC/BTM-SAL/28882/2017), and the NORTE 2020 Structured Project, co-funded by Norte2020 (NORTE-01-0145-FEDER-000021). This research was also partially supported by national funds by FCT through the projects UIDB/04423/2020 and UIDP/04423/2020 (Group of Natural Products and Medicinal Chemistry-CIIMAR) and ERDF, through the COMPETE—POFC program in the framework of the program PT2020

Echinacea purpurea fractions represent promising plant-based anti-inflammatory formulations

Echinacea purpurea is traditionally used in the treatment of inflammatory diseases. Therefore, we investigated the anti-inflammatory capacity of E. purpurea dichloromethanolic (DE) and ethanolic extracts obtained from flowers and roots (R). To identify the class of compounds responsible for the strongest bioactivity, the extracts were fractionated into phenol/carboxylic acid (F1) and alkylamide fraction (F2). The chemical fingerprint of bioactive compounds in the fractions was evaluated by LC-HRMS. E. purpurea extracts and fractions significantly reduced pro-inflammatory cytokines (interleukin 6 and/or tumor necrosis factor) and reactive oxygen and nitrogen species (ROS/RNS) production by lipopolysaccharide-stimulated primary human monocyte-derived macrophages. Dichloromethanolic extract obtained from roots (DE-R) demonstrated the strongest anti-inflammatory activity. Moreover, fractions exhibited greater anti-inflammatory activity than whole extract. Indeed, alkylamides must be the main compounds responsible for the anti-inflammatory activity of extracts; thus, the fractions presenting high content of these compounds presented greater bioactivity. It was demonstrated that alkylamides exert their anti-inflammatory activity through the downregulation of the phosphorylation of p38, ERK 1/2, STAT 3, and/or NF-κB signaling pathways, and/or downregulation of cyclooxygenase 2 expression. E. purpurea extracts and fractions, mainly DE-R-F2, are promising and powerful plant-based anti-inflammatory formulations that can be further used as a basis for the treatment of inflammatory diseases.This work was financially supported by the FCT to the Ph.D. grants of S.F.V. (PD/BD/135246/2017 and COVID/BD/152012/2021), S.M.G. (SFRH/BD/136814/2018), and C.C. (CEECIND/04058/2018), and the projects PATH (PD/00169/2013), HEALTH-UNORTE (NORTE-01- 0145-FEDER-000039) and the NORTE 2020 Structured Project, co-funded by Norte2020 (NORTE-01- 0145-FEDER-000021

Macrophages and myeloid dendritic cells, but not plasmacytoid dendritic cells, produce IL-10 in response to MyD88- and TRIF-dependent TLR signals, and TLR-independent signals

We have previously reported that mouse plasmacytoid dendritic cells (DC) produce high levels of IL-12p70, whereas bone marrow-derived myeloid DC and splenic DC produce substantially lower levels of this cytokine when activated with the TLR-9 ligand CpG. We now show that in response to CpG stimulation, high levels of IL-10 are secreted by macrophages, intermediate levels by myeloid DC, but no detectable IL-10 is secreted by plasmacytoid DC. MyD88-dependent TLR signals (TLR4, 7, 9 ligation), Toll/IL-1 receptor domain-containing adaptor-dependent TLR signals (TLR3, 4 ligation) as well as non-TLR signals (CD40 ligation) induced macrophages and myeloid DC to produce IL-10 in addition to proinflammatory cytokines. IL-12p70 expression in response to CpG was suppressed by endogenous IL-10 in macrophages, in myeloid DC, and to an even greater extent in splenic CD8alpha(-) and CD8alpha(+) DC. Although plasmacytoid DC did not produce IL-10 upon stimulation, addition of this cytokine exogenously suppressed their production of IL-12, TNF, and IFN-alpha, showing trans but not autocrine regulation of these cytokines by IL-10 in plasmacytoid DC

Association between Residences in U.S. Northern Latitudes and Rheumatoid Arthritis: A Spatial Analysis of the Nurses’ Health Study

Background: The etiology of rheumatoid arthritis (RA) remains largely unknown, although epidemiologic studies suggest genetic and environmental factors may play a role. Geographic variation in incident RA has been observed at the regional level. Objective: Spatial analyses are a useful tool for confirming existing exposure hypotheses or generating new ones. To further explore the association between location and RA risk, we analyzed individual-level data from U.S. women in the Nurses’ Health Study, a nationwide cohort study. Methods: Participants included 461 incident RA cases and 9,220 controls with geocoded addresses; participants were followed from 1988 to 2002. We examined spatial variation using addresses at baseline in 1988 and at the time of case diagnosis or the censoring of controls. Generalized additive models (GAMs) were used to predict a continuous risk surface by smoothing on longitude and latitude while adjusting for known risk factors. Permutation tests were conducted to evaluate the overall importance of location and to identify, within the entire study area, those locations of statistically significant risk. Results: A statistically significant area of increased RA risk was identified in the northeast United States (p-value = 0.034). Risk was generally higher at northern latitudes, and it increased slightly when we used the nurses’ 1988 locations compared with those at the time of diagnosis or censoring. Crude and adjusted models produced similar results. Conclusions: Spatial analyses suggest women living in higher latitudes may be at greater risk for RA. Further, RA risk may be greater for locations that occur earlier in residential histories. These results illustrate the usefulness of GAM methods in generating hypotheses for future investigation and supporting existing hypotheses

Human Papillomavirus E6 Triggers Upregulation of the Antiviral and Cancer Genomic DNA Deaminase APOBEC3B

ABSTRACT Several recent studies have converged upon the innate immune DNA cytosine deaminase APOBEC3B (A3B) as a significant source of genomic uracil lesions and mutagenesis in multiple human cancers, including those of the breast, head/neck, cervix, bladder, lung, ovary, and other tissues. A3B is upregulated in these tumor types relative to normal tissues, but the mechanism is unclear. Because A3B also has antiviral activity in multiple systems and is a member of the broader innate immune response, we tested the hypothesis that human papillomavirus (HPV) infection causes A3B upregulation. We found that A3B mRNA expression and enzymatic activity were upregulated following transfection of a high-risk HPV genome and that this effect was abrogated by inactivation of E6. Transduction experiments showed that the E6 oncoprotein alone was sufficient to cause A3B upregulation, and a panel of high-risk E6 proteins triggered higher A3B levels than did a panel of low-risk or noncancer E6 proteins. Knockdown experiments in HPV-positive cell lines showed that endogenous E6 is required for A3B upregulation. Analyses of publicly available head/neck cancer data further support this relationship, as A3B levels are higher in HPV-positive cancers than in HPV-negative cancers. Taken together with the established role for high-risk E6 in functional inactivation of TP53 and published positive correlations in breast cancer between A3B upregulation and genetic inactivation of TP53, our studies suggest a model in which high-risk HPV E6, possibly through functional inactivation of TP53, causes derepression of A3B gene transcription. This would lead to a mutator phenotype that explains the observed cytosine mutation biases in HPV-positive head/neck and cervical cancers

Optimizing land use decision-making to sustain Brazilian agricultural profits, biodiversity and ecosystem services

AbstractDesigning landscapes that can meet human needs, while maintaining functioning ecosystems, is essential for long-term sustainability. To achieve this goal, we must better understand the trade-offs and thresholds in the provision of ecosystem services and economic returns. To this end, we integrate spatially explicit economic and biophysical models to jointly optimize agricultural profit (sugarcane production and cattle ranching), biodiversity (bird and mammal species), and freshwater quality (nitrogen, phosphorus, and sediment retention) in the Brazilian Cerrado. We generate efficiency frontiers to evaluate the economic and environmental trade-offs and map efficient combinations of agricultural land and natural habitat under varying service importance. To assess the potential impact of the Brazilian Forest Code (FC), a federal policy that aims to promote biodiversity and ecosystem services on private lands, we compare the frontiers with optimizations that mimic the habitat requirements in the region. We find significant opportunities to improve both economic and environmental outcomes relative to the current landscape. Substantial trade-offs between biodiversity and water quality exist when land use planning targets a single service, but these trade-offs can be minimized through multi-objective planning. We also detect non-linear profit-ecosystem services relationships that result in land use thresholds that coincide with the FC requirements. Further, we demonstrate that landscape-level planning can greatly improve the performance of the FC relative to traditional farm-level planning. These findings suggest that through joint planning for economic and environmental goals at a landscape-scale, Brazil's agricultural sector can expand production and meet regulatory requirements, while maintaining biodiversity and ecosystem service provision

An evidence-base for the implementation of hospital-based palliative care programs in routine cancer practice:A systematic review

Background: Despite global support, there remain gaps in the integration of early palliative care into cancer care. The methods of implementation whereby evidence of benefits of palliative care is translated into practice deserve attention. Aim: To identify implementation frameworks utilised in integrated palliative care in hospital-based oncology services and to describe the associated enablers and barriers to service integration. Design: Systematic review with a narrative synthesis including qualitative, mixed methods, pre-post and quasi experimental designs following the guidance by the Centre for Reviews and Dissemination (PROSPERO registration CRD42021252092). Data sources: Six databases searched in 2021: EMBASE, EMCARE, APA PsycINFO, CINAHL, Cochrane Library and Ovid MEDLINE searched in 2023. Included were qualitative or quantitative studies, in English language, involving adults >18 years, and implementing hospital-based palliative care into cancer care. Critical appraisal tools were used to assess the quality and rigour. Results: Seven of the 16 studies explicitly cited the use of frameworks including those based on RE-AIM, Medical Research Council evaluation of complex interventions and WHO constructs of health service evaluation. Enablers included an existing supportive culture, clear introduction to the programme across services, adequate funding, human resources and identification of advocates. Barriers included a lack of communication with the patients, caregivers, physicians and palliative care team about programme goals, stigma around the term ‘palliative’, a lack of robust training, or awareness of guidelines and undefined staff roles. Conclusions: Implementation science frameworks provide a method to underpin programme development and evaluation as palliative care is integrated within the oncology setting.Farwa Rizvi, Helen Elizabeth Wilding, Nicole M Rankin, Roslyn Le Gautier, Lorna Gurren, Vijaya Sundararajan, Kylee Bellingham, Joyce Chua, Gregory B Crawford, Anna K Nowak, Brian Le, Geoff Mitchell, Sue-Anne McLachlan, Tanara Vieira Sousa, Robyn Hudson, Maarten IJzerman, Anna Collins, and Jennifer Phili