Positioning by multicell fingerprinting in urban NB-IoT networks

Narrowband Internet of Things (NB-IoT) has quickly become a leading technology in the deployment of IoT systems and services, owing to its appealing features in terms of coverage and energy efficiency, as well as compatibility with existing mobile networks. Increasingly, IoT services and applications require location information to be paired with data collected by devices; NB-IoT still lacks, however, reliable positioning methods. Time-based techniques inherited from long-term evolution (LTE) are not yet widely available in existing networks and are expected to perform poorly on NB-IoT signals due to their narrow bandwidth. This investigation proposes a set of strategies for NB-IoT positioning based on fingerprinting that use coverage and radio information from multiple cells. The proposed strategies were evaluated on two large-scale datasets made available under an open-source license that include experimental data from multiple NB-IoT operators in two large cities: Oslo, Norway, and Rome, Italy. Results showed that the proposed strategies, using a combination of coverage and radio information from multiple cells, outperform current state-of-the-art approaches based on single cell fingerprinting, with a minimum average positioning error of about 20 m when using data for a single operator that was consistent across the two datasets vs. about 70 m for the current state-of-the-art approaches. The combination of data from multiple operators and data smoothing further improved positioning accuracy, leading to a minimum average positioning error below 15 m in both urban environments

Clathrin switches transforming growth factor-β role to pro-tumorigenic in liver cancer

Background & Aims: Upon ligand binding, tyrosine kinase receptors, such as epidermal growth factor receptor (EGFR), are recruited into clathrin-coated pits for internalization by endocytosis, which is relevant for signalling and/or receptor degradation. In liver cells, transforming growth factor-beta (TGF-beta) induces both pro- and anti-apoptotic signals; the latter are mediated by the EGFR pathway. Since EGFR mainly traffics via clathrin-coated vesicles, we aimed to analyse the potential role of clathrin in TGF-beta-induced signalling in liver cells and its relevance in liver cancer. Methods: Real-Time PCR and immunohistochemistry were used to analyse clathrin heavy-chain expression in human (CLTC) and mice (Cltc) liver tumours. Transient knockdown (siRNA) or overexpression of CLTC were used to analyse its role on TGF-beta and EGFR signalling in vitro. Bioinformatic analysis was used to determine the effect of CLTC and TGEB1 expression on prognosis and overall survival in patients with hepatocellular carcinoma (HCC). Results: Clathrin expression increased during liver tumorigenesis in humans and mice. CLTC knockdown cells responded to TGF-beta phosphorylating SMADs (canonical signalling) but showed impairment in the anti-apoptotic signals (EGFR transactivation). Experiments of loss or gain of function in HCC cells reveal an essential role for clathrin in inhibiting TGF-beta-induced apoptosis and upregulation of its pro-apoptotic target NOX4. Autocrine TGF-beta signalling in invasive HCC cells upregulates CLTC expression, switching its role to pro-tumorigenic. A positive correlation between TGEB1 and CLTC was found in HCC cells and patients. Patients expressing high levels of TGEB1 and CLTC had a worse prognosis and lower overall survival. Conclusions: This work describes a novel role for clathrin in liver tumorigenesis, favouring non-canonical pro-tumorigenic TGF-beta pathways. CLTC expression in human HCC samples could help select patients that would benefit from TGF-beta-targeted therapy. Lay summary: Clathrin heavy-chain expression increases during liver tumorigenesis in humans (CLTC) and mice (Mc), altering the cellular response to TGF-beta in favour of anti-apoptotic/pro-tumorigenic signals. A positive correlation between TGEB1 and CLTC was found in HCC cells and patients. Patients expressing high levels of TGEB1 and CLTC had a worse prognosis and lower overall survival. CLTC expression in HCC human samples could help select patients that would benefit from therapies targeting TGF-beta. (C) 2019 European Association for the Study of the Liver. Published by Elsevier B

Molecular profiling and feasibility using a comprehensive hybrid capture panel on a consecutive series of non-small-cell lung cancer patients from a single centre

Background: Targeted next-generation sequencing (NGS) is recommended to screen actionable genomic alterations (GAs) in patients with non-small-cell lung cancer (NSCLC). We determined the feasibility to detect actionable GAs using TruSight™ Oncology 500 (TSO500) in 200 consecutive patients with NSCLC. Materials and methods: DNA and RNA were sequenced on an Illumina® NextSeq 550 instrument and processed using the TSO500 Docker pipeline. Clinical actionability was defined within the molecular tumour board following European Society for Medical Oncology (ESMO) guidelines for oncogene-addicted NSCLC. Overall survival (OS) was estimated as per the presence of druggable GAs and treatment with targeted therapy. Results: Most patients were males (69.5%) and former or current smokers (86.5%). Median age was 64 years. The most common histological type and tumour stage were lung adenocarcinoma (81%) and stage IV (64%), respectively. Sequencing was feasible in most patients (93.5%) and actionable GAs were found in 26.5% of patients. A high concordance was observed between single-gene testing and TSO500 NGS panel. Patients harbouring druggable GAs and receiving targeted therapy achieved longer OS compared to patients without druggable GAs. Conversely, patients with druggable GAs not receiving targeted therapy had a trend toward shorter OS compared with driver-negative patients. Conclusions: Hybrid capture sequencing using TSO500 panel is feasible to analyse clinical samples from patients with NSCLC and is an efficient tool for screening actionable GAs

Dissecting the role of the NADPH oxidase NOX4 in TGF-beta signaling in hepatocellular carcinoma

The NADPH oxidase NOX4 has been proposed as necessary for the apoptosis induced by the Transforming Growth Factor-beta (TGF-I3) in hepatocytes and hepatocellular carcinoma (HCC) cells. However, whether NOX4 is required for TGF-I3-induced canonical (SMADs) or non-canonical signals is not fully understood yet, neither its potential involvement in other parallel actions induced by TGF-I3. In this work we have used CRISPR Cas9 technology to stable attenuate NOX4 expression in HCC cells. Results have indicated that NOX4 is required for an efficient SMAD2/3 phosphorylation in response to TGF-I3, whereas non-canonical signals, such as the phos-phorylation of the Epidermal Growth Receptor or AKT, are higher in NOX4 silenced cells. TGF-I3-mediated in-hibition of cell proliferation and viability is attenuated in NOX4 silenced cells, correlating with decreased response in terms of apoptosis, and maintenance of high expression of MYC and CYCLIN D1. These results would indicate that NOX4 is required for all the tumor suppressor actions of TGF-I3 in HCC. However, analysis in human HCC tumors has revealed a worse prognosis for patients showing high expression of TGF-I31-related genes concomitant with high expression of NOX4. Deepening into other tumorigenic actions of TGF-I3 that may contribute to tumor progression, we found that NOX4 is also required for TGF-I3-induced migratory effects. The Epithelial-Mesenchymal transition (EMT) program does not appear to be affected by attenuation of NOX4 levels. However, TGF-I3-mediated regulation of cytoskeleton dynamics and focal adhesions require NOX4, which is necessary for TGF-I3-induced increase in the chaperone Hsp27 and correct subcellular localization of Hic-5 within focal adhesions, as well for upregulation of the metalloprotease MMP9. All these results together point to NOX4 as a key element in the whole TGF-I3 signaling in HCC cells, revealing an unknown role for NOX4 as tumor promoter in HCC patients presenting activation of the TGF-I3 pathway

Türkiye’de bulunan yoğun bakımlarda sabun, kağıt havlu ve alkol bazlı el dezenfektanı yeterli mi?: Phokai çalışması sonuçları

Introduction: Hand hygiene is one of the most effective infection control measures to prevent the spread of healthcare-associated infections (HCAI). Water, soap, paper towel and hand disinfectant must be available and adequate in terms of effective hand hygiene. The adequacy of hand hygiene products or keeping water-soap and paper towel is still a problem for many developing countries like Turkey. In this multicenter study, we analyzed the adequacy in number and availability of hand hygiene products.Materials and Methods: This study was performed in all intensive care units (ICUs) of 41 hospitals (27 tertiary-care educational, 10 state and four private hospitals) from 22 cities located in seven geographical regions of Turkey. We analyzed water, soap, paper towel and alcohol-based hand disinfectant adequacy on four different days, two of which were in summer during the vacation time (August, 27th and 31st 2016) and two in autumn (October, 12th and 15th 2016).Results: The total number of ICUs and intensive care beds in 41 participating centers were 214 and 2357, respectively. Overall, there was no soap in 3-11% of sinks and no paper towel in 10-18% of sinks while there was no alcohol-based hand disinfectant in 1-4.7% of hand disinfectant units on the observation days. When we compared the number of sinks with soap and/or paper towel on weekdays vs. weekends, there was no significant difference in summer. However, on autumn weekdays, the number of sinks with soap and paper towel was significantly lower on weekend days (p<0.0001, p<0.0001) while the number of hand disinfectant units with alcohol-based disinfectant was significantly higher (p<0.0001).Conclusion: There should be adequate and accessible hand hygiene materials for effective hand hygiene. In this study, we found that soap and paper towels were inadequate on the observation days in 3-11% and 10-18% of units, respectively. Attention should be paid on soap and paper towel supply at weekends as well

Understanding of sub-band gap absorption of femtosecond-laser sulfur hyperdoped silicon using synchrotron-based techniques

[[abstract]]The correlation between sub-band gap absorption and the chemical states and electronic and atomic structures of S-hyperdoped Si have been extensively studied, using synchrotron-based x-ray photoelectron spectroscopy (XPS), x-ray absorption near-edge spectroscopy (XANES), extended x-ray absorption fine structure (EXAFS), valence-band photoemission spectroscopy (VB-PES) and first-principles calculation. S 2p XPS spectra reveal that the S-hyperdoped Si with the greatest (~87%) sub-band gap absorption contains the highest concentration of S2− (monosulfide) species. Annealing S-hyperdoped Si reduces the sub-band gap absorptance and the concentration of S2− species, but significantly increases the concentration of larger S clusters [polysulfides (Sn2−, n &gt; 2)]. The Si K-edge XANES spectra show that S hyperdoping in Si increases (decreased) the occupied (unoccupied) electronic density of states at/above the conduction-band-minimum. VB-PES spectra evidently reveal that the S-dopants not only form an impurity band deep within the band gap, giving rise to the sub-band gap absorption, but also cause the insulator-to-metal transition in S-hyperdoped Si samples. Based on the experimental results and the calculations by density functional theory, the chemical state of the S species and the formation of the S-dopant states in the band gap of Si are critical in determining the sub-band gap absorptance of hyperdoped Si samples.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SCI[[ispeerreviewed]]Y[[booktype]]電子版[[countrycodes]]GB

A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan

BackgroundAging is associated with increased levels of reactive oxygen species and inflammation that disrupt proteostasis and mitochondrial function and leads to organism-wide frailty later in life. ARA290 (cibinetide), an 11-aa non-hematopoietic peptide sequence within the cardioprotective domain of erythropoietin, mediates tissue protection by reducing inflammation and fibrosis. Age-associated cardiac inflammation is linked to structural and functional changes in the heart, including mitochondrial dysfunction, impaired proteostasis, hypertrophic cardiac remodeling, and contractile dysfunction. Can ARA290 ameliorate these age-associated cardiac changes and the severity of frailty in advanced age?MethodsWe conducted an integrated longitudinal (n = 48) and cross-sectional (n = 144) 15 months randomized controlled trial in which 18-month-old Fischer 344 x Brown Norway rats were randomly assigned to either receive chronic ARA290 treatment or saline. Serial echocardiography, tail blood pressure and body weight were evaluated repeatedly at 4-month intervals. A frailty index was calculated at the final timepoint (33 months of age). Tissues were harvested at 4-month intervals to define inflammatory markers and left ventricular tissue remodeling. Mitochondrial and myocardial cell health was assessed in isolated left ventricular myocytes. Kaplan–Meier survival curves were established. Mixed ANOVA tests and linear mixed regression analysis were employed to determine the effects of age, treatment, and age-treatment interactions.ResultsChronic ARA290 treatment mitigated age-related increases in the cardiac non-myocyte to myocyte ratio, infiltrating leukocytes and monocytes, pro-inflammatory cytokines, total NF-κB, and p-NF-κB. Additionally, ARA290 treatment enhanced cardiomyocyte autophagy flux and reduced cellular accumulation of lipofuscin. The cardiomyocyte mitochondrial permeability transition pore response to oxidant stress was desensitized following chronic ARA290 treatment. Concurrently, ARA290 significantly blunted the age-associated elevation in blood pressure and preserved the LV ejection fraction. Finally, ARA290 preserved body weight and significantly reduced other markers of organism-wide frailty at the end of life.ConclusionAdministration of ARA290 reduces cell and tissue inflammation, mitigates structural and functional changes within the cardiovascular system leading to amelioration of frailty and preserved healthspan

Self-reported antibiotic stewardship and infection control measures from 57 intensive care units: An international ID-IRI survey

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (similar to 5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&amp;50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted. (C) 2022 Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences