A Case Study in the Future Challenges in Electricity Grid Infrastructure

The generation by renewables and the loading by electrical vehicle charging imposes severe challenges in the redesign of today’s power supply systems. Indeed, accommodating these emerging power sources and sinks requires traditional power systems to evolve from rigid centralized unidirectional architectures to intelligent decentralized entities allowing a bidirectional power flow. In the case study proposed by ENDINET, we investigate how the penetration of solar panels and of battery charging stations on large scale affects the voltage quality and loss level in a distribution network servicing a residential area in Eindhoven, NL. In our case study we take the average household load during summer and winter into account and consider both a radial and meshed topology of the network. Our study results for both topologies considered in a quantification of the levels of penetration and a strategy for electrical vehicle loading strategy that meet the voltage and loss requirements in the network

Comparative cellular analysis of motor cortex in human, marmoset and mouse

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals(1). Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.Cardiovascular Aspects of Radiolog

Quadriceps Strength and Executive Functions in Older Women.

Objective: The aim of this study is to answer the question whether the strength of the knee extensor musculus quadriceps (m. quadriceps), in particular, is related to specific executive functions and whether this relationship is independent of aerobic fitness. The clinical relevance of this question is that the m. quadriceps can still be trained in older people and executive functions are the most vulnerable to processes of aging. Design: In 41 cognitively intact older women, cognitive functioning was assessed by neuropsychological tests; isometric and isotonic quadriceps strength by the Quadrisotester and the 30-sec chair-stand test, respectively; and aerobic fitness by the 6-min walk test. Results: A significant proportion of the total variance of the executive functions, attention/working memory and inhibition, were explained by isometric/isotonic knee extensor strength and aerobic fitness, respectively. Extensor muscle strength, aerobic fitness, or one or more interactions did not explain a significant proportion of the total variance of other cognitive functions. Conclusions: These data suggest that in older women, quadriceps strength is associated with the executive function, attention/working memory, and that this effect is independent of aerobic fitness, which seems to be associated more strongly with inhibition, another executive function

Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial

Contains fulltext : 228545.pdf (Publisher’s version ) (Open Access

Association Between Immune-Related Adverse Events and Recurrence-Free Survival Among Patients With Stage III Melanoma Randomized to Receive Pembrolizumab or Placebo A Secondary Analysis of a Randomized Clinical Trial

Contains fulltext : 218502.pdf (Publisher’s version ) (Open Access

Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma

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Prognostic and predictive value of AJCC-8 staging in the phase III EORTC1325/KEYNOTE-054 trial of pembrolizumab vs placebo in resected high-risk stage III melanoma

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A Case Study in the Future Challenges in Electricity Grid Infrastructure

The generation by renewables and the loading by electrical vehicle charging imposes severe challenges in the redesign of today’s power supply systems. Indeed, accommodating these emerging power sources and sinks requires traditional power systems to evolve from rigid centralized unidirectional architectures to intelligent decentralized entities allowing a bidirectional power flow. In the case study proposed by ENDINET, we investigate how the penetration of solar panels and of battery charging stations on large scale affects the voltage quality and loss level in a distribution network servicing a residential area in Eindhoven, NL. In our case study we take the average household load during summer and winter into account and consider both a radial and meshed topology of the network. Our study results for both topologies considered in a quantification of the levels of penetration and a strategy for electrical vehicle loading strategy that meet the voltage and loss requirements in the network

Reply to E. Hindié

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Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 trial in patients with resected, high-risk stage III melanoma demonstrated improved recurrence-free survival with adjuvant pembrolizumab compared with placebo (hazard ratio 0·57 [98·4% CI 0·43-0·74]; p<0·0001). This study reports the results from the health-related quality-of-life (HRQOL) exploratory endpoint. METHODS: This double-blind, randomised, controlled, phase 3 trial was done at 123 academic centres and community hospitals across 23 countries. Patients aged 18 years or older with previously untreated histologically confirmed stage IIIA, IIIB, or IIIC resected cutaneous melanoma, and an Eastern Cooperative Oncology Group performance status score of 1 or 0 were eligible. Patients were randomly assigned (1:1) using a central interactive voice-response system on the basis of a minimisation technique stratified for stage and geographic region to receive intravenously 200 mg pembrolizumab or placebo. Treatment was administered every 3 weeks for 1 year, or until disease recurrence, unacceptable toxicity, or death. The primary endpoint of the trial was recurrence-free survival (reported elsewhere). HRQOL was a prespecified exploratory endpoint, with global health/quality of life (GHQ) over 2 years measured by the EORTC QLQ-C30 as the primary analysis. Analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37, and long-term follow-up is ongoing. FINDINGS: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to pembrolizumab (n=514) or placebo (n=505). Median follow-up was 15·1 months (IQR 12·8-16·9) at the time of this analysis. HRQOL compliance was greater than 90% at baseline, greater than 70% during the first year, and greater than 60% thereafter for both groups. Because of low absolute compliance numbers at later follow-up, the analysis was truncated to week 84. Baseline GHQ scores were similar between groups (77·55 [SD 18·20] in the pembrolizumab group and 76·54 [17·81] in the placebo group) and remained stable over time. The difference in average GHQ score between the two groups over the 2 years was -2·2 points (95% CI -4·3 to -0·2). The difference in average score during treatment was -1·1 points (95% CI -3·2 to 0·9) and the difference in average score after treatment was -2·2 points (-4·8 to 0·4). These differences are within the 5-point clinical relevance threshold for the QLQ-C30 and are therefore clinically non-significant. INTERPRETATION: Pembrolizumab does not result in a clinically significant decrease in HRQOL compared with placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting. FUNDING: Merck Sharp & Dohme