145 research outputs found

    Real-World Implementation of Reinforcement Learning Based Energy Coordination for a Cluster of Households

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    Given its substantial contribution of 40\% to global power consumption, the built environment has received increasing attention to serve as a source of flexibility to assist the modern power grid. In that respect, previous research mainly focused on energy management of individual buildings. In contrast, in this paper, we focus on aggregated control of a set of residential buildings, to provide grid supporting services, that eventually should include ancillary services. In particular, we present a real-life pilot study that studies the effectiveness of reinforcement-learning (RL) in coordinating the power consumption of 8 residential buildings to jointly track a target power signal. Our RL approach relies solely on observed data from individual households and does not require any explicit building models or simulators, making it practical to implement and easy to scale. We show the feasibility of our proposed RL-based coordination strategy in a real-world setting. In a 4-week case study, we demonstrate a hierarchical control system, relying on an RL-based ranking system to select which households to activate flex assets from, and a real-time PI control-based power dispatch mechanism to control the selected assets. Our results demonstrate satisfactory power tracking, and the effectiveness of the RL-based ranks which are learnt in a purely data-driven manner.Comment: 8 pages, 2 figures, workshop article accepted at RLEM'23 (BuildSys'23

    Putative DNA G-quadruplex formation within the promoters of Plasmodium falciparum var genes

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    Background. Guanine-rich nucleic acid sequences are capable of folding into an intramolecular four-stranded structure called a G-quadruplex. When found in gene promoter regions, G-quadruplexes can downregulate gene expression, possibly by blocking the transcriptional machinery. Here we have used a genome-wide bioinformatic approach to identify Putative G-Quadruplex Sequences (PQS) in the Plasmodium falciparum genome, along with biophysical techniques to examine the physiological stability of P. falciparum PQS in vitro. Results. We identified 63 PQS in the non-telomeric regions of the P. falciparum clone 3D7. Interestingly, 16 of these PQS occurred in the upstream region of a subset of the P. falciparum var genes (group B var genes). The var gene family encodes PfEMP1, the parasite’s major variant antigen and adhesin expressed at the surface of infected erythrocytes, that plays a key role in malaria pathogenesis and immune evasion. The ability of the PQS found in the upstream regions of group B var genes (UpsB-Q) to form stable Gquadruplex structures in vitro was confirmed using 1H NMR, circular dichroism, UV spectroscopy, and thermal denaturation experiments. Moreover, the synthetic compound BOQ1 that shows a higher affinity for DNA forming quadruplex rather than duplex structures was found to bind with high affinity to the UpsB-Q. Conclusions. This is the first demonstration of non-telomeric PQS in the genome of P. falciparum that form stable G-quadruplexes under physiological conditions in vitro. These results allow the generation of a novel hypothesis that the G-quadruplex sequences in the upstream regions of var genes have the potential to play a role in the transcriptional control of this major virulence-associated multi-gene family

    The effect of lip closure on palatal growth in patients with unilateral clefts

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    Objectives The objective of this study was to compare maxillary dimensions and growth in newborns with Complete Unilateral Cleft Lip and Palate (UCLP) to healthy newborns before and after cheiloplasty. Additionally, a palatal growth curve is constructed to give more information about the natural growth before surgical intervention. Methods Twenty-eight newborns with complete UCLP were enrolled in this study. Multiple plaster-casts of each child during their first year were collected and grouped in before and after cheiloplasty. A previous developed semi-automatic segmentation tool was used to assess the maxillary dimensions and were compared to a healthy control group. Z-scores were calculated to indicate differences between the two populations and if cheiloplasty had influence on maxillary growth. Furthermore, the prediction model created in a previous study was used to indicate differences between predictions and the outcome in UCLP measurements. The analysis was tested for inter- and intra-observer variability. Results Results show differences in alveolar and palatal shape in UCLP patients in comparison with healthy controls. Prior to cheiloplasty an increased width and alveolar length was observed while the palatal depth was decreased. After cheiloplasty the widths moved towards normal but were still significantly larger

    Crosstalk between androgen receptor and WNT/β-catenin signaling causes sex-specific adrenocortical hyperplasia in mice

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    Female bias is highly prevalent in conditions such as adrenal cortex hyperplasia and neoplasia, but the reasons behind this phenomenon are poorly understood. In this study, we show that overexpression of the secreted WNT agonist R-spondin 1 (RSPO1) leads to ectopic activation of WNT/β-catenin signaling and causes sex-specific adrenocortical hyperplasia in mice. Although female adrenals show ectopic proliferation, male adrenals display excessive immune system activation and cortical thinning. Using a combination of genetic manipulations and hormonal treatment, we show that gonadal androgens suppress ectopic proliferation in the adrenal cortex and determine the selective regulation of the WNT-related genes Axin2 and Wnt4. Notably, genetic removal of androgen receptor (AR) from adrenocortical cells restores the mitogenic effect of WNT/β-catenin signaling. This is the first demonstration that AR activity in the adrenal cortex determines susceptibility to canonical WNT signaling-induced hyperplasia.</p

    Prognostic Accuracy of Sepsis-3 Criteria for In-Hospital Mortality Among Patients With Suspected Infection Presenting to the Emergency Department.

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    An international task force recently redefined the concept of sepsis. This task force recommended the use of the quick Sequential Organ Failure Assessment (qSOFA) score instead of systemic inflammatory response syndrome (SIRS) criteria to identify patients at high risk of mortality. However, these new criteria have not been prospectively validated in some settings, and their added value in the emergency department remains unknown. To prospectively validate qSOFA as a mortality predictor and compare the performances of the new sepsis criteria to the previous ones. International prospective cohort study, conducted in France, Spain, Belgium, and Switzerland between May and June 2016. In the 30 participating emergency departments, for a 4-week period, consecutive patients who visited the emergency departments with suspected infection were included. All variables from previous and new definitions of sepsis were collected. Patients were followed up until hospital discharge or death. Measurement of qSOFA, SOFA, and SIRS. In-hospital mortality. Of 1088 patients screened, 879 were included in the analysis. Median age was 67 years (interquartile range, 47-81 years), 414 (47%) were women, and 379 (43%) had respiratory tract infection. Overall in-hospital mortality was 8%: 3% for patients with a qSOFA score lower than 2 vs 24% for those with qSOFA score of 2 or higher (absolute difference, 21%; 95% CI, 15%-26%). The qSOFA performed better than both SIRS and severe sepsis in predicting in-hospital mortality, with an area under the receiver operating curve (AUROC) of 0.80 (95% CI, 0.74-0.85) vs 0.65 (95% CI, 0.59-0.70) for both SIRS and severe sepsis (P &lt; .001; incremental AUROC, 0.15; 95% CI, 0.09-0.22). The hazard ratio of qSOFA score for death was 6.2 (95% CI, 3.8-10.3) vs 3.5 (95% CI, 2.2-5.5) for severe sepsis. Among patients presenting to the emergency department with suspected infection, the use of qSOFA resulted in greater prognostic accuracy for in-hospital mortality than did either SIRS or severe sepsis. These findings provide support for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria in the emergency department setting. clinicaltrials.gov Identifier: NCT02738164

    Association between Malnutrition Assessed by the Global Leadership Initiative on Malnutrition Criteria and Mortality in Older People: A Scoping Review.

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    peer reviewedThe Global Leadership Initiative on Malnutrition (GLIM) criteria were introduced in 2018 for the diagnosis of malnutrition in adults. This review was aimed at gathering the evidence about the association between malnutrition according to the GLIM criteria and mortality in older people, an emerging and clinically meaningful topic in the implementation of the GLIM criteria in geriatric healthcare settings. This scoping review considered meta-analyses, systematic reviews, cohort studies, and cross-sectional studies published in PubMed, Scopus, and the Cochrane Database for Systematic Reviews from the development of the GLIM criteria in 2018 to January 2023. Seventeen articles (15 cohort and 2 cross-sectional studies) were included. The association between GLIM criteria and mortality had been assessed in hospitalized (11 over the 17 articles) and community-dwelling older populations, and those in nursing homes. The review found a strong association between malnutrition according to GLIM criteria and mortality in hospitalized (1.2-fold to 7-fold higher mortality) and community-dwelling older people (1.6-fold to 4-fold higher mortality). These findings highlight the prognostic value of the GLIM criteria and support strategies towards the implementation of malnutrition evaluation according to the GLIM, in order to optimize comprehensive geriatric assessment and provide older people with the highest quality of nutritional care. Studies in nursing home populations were very scarce and may be urgently required

    Long-term evidence for ecological intensification as a pathway to sustainable agriculture

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    Ecological intensification (EI) could help return agriculture into a 'safe operating space' for humanity. Using a novel application of meta-analysis to data from 30 long-term experiments from Europe and Africa (comprising 25,565 yield records), we investigated how field-scale EI practices interact with each other, and with N fertilizer and tillage, in their effects on long-term crop yields. Here we confirmed that EI practices (specifically, increasing crop diversity and adding fertility crops and organic matter) have generally positive effects on the yield of staple crops. However, we show that EI practices have a largely substitutive interaction with N fertilizer, so that EI practices substantially increase yield at low N fertilizer doses but have minimal or no effect on yield at high N fertilizer doses. EI practices had comparable effects across different tillage intensities, and reducing tillage did not strongly affect yields.Intensifying food production sustainably is critical given growing demand and agriculture's environmental footprint. This meta-analysis finds that practices such as adding organic matter and increasing crop diversity can partly substitute for nitrogen fertilizer to sustain or increase yields

    Crosstalk between androgen receptor and WNT/β-catenin signaling causes sex-specific adrenocortical hyperplasia in mice

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    Female bias is highly prevalent in conditions such as adrenal cortex hyperplasia and neoplasia, but the reasons behind this phenomenon are poorly understood. In this study, we show that overexpression of the secreted WNT agonist R-spondin 1 (RSPO1) leads to ectopic activation of WNT/β-catenin signaling and causes sex-specific adrenocortical hyperplasia in mice. Although female adrenals show ectopic proliferation, male adrenals display excessive immune system activation and cortical thinning. Using a combination of genetic manipulations and hormonal treatment, we show that gonadal androgens suppress ectopic proliferation in the adrenal cortex and determine the selective regulation of the WNT-related genes Axin2 and Wnt4. Notably, genetic removal of androgen receptor (AR) from adrenocortical cells restores the mitogenic effect of WNT/β-catenin signaling. This is the first demonstration that AR activity in the adrenal cortex determines susceptibility to canonical WNT signaling-induced hyperplasia

    Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer:A Randomized Clinical Trial

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    PURPOSE:Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking.METHODS:Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior &lt;.0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality.RESULTS:Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior =.0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior =.0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first (P =.4940).CONCLUSION:On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.</p
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