Manipulation and Generation of Supercurrent in Out-of-Equilibrium Josephson Tunnel Nanojunctions

We demonstrate experimentally manipulation of supercurrent in Al-AlO_x-Ti Josephson tunnel junctions by injecting quasiparticles in a Ti island from two additional tunnel-coupled Al superconducting reservoirs. Both supercurrent enhancement and quenching with respect to equilibrium are achieved. We demonstrate cooling of the Ti line by quasiparticle injection from the normal state deep into the superconducting phase. A model based on heat transport and non-monotonic current-voltage characteristic of a Josephson junction satisfactorily accounts for our findings.Comment: 4 pages, 4 colour figures, published versio

Diagnosis of right bundle branch block: a concordance study

Bundle branch block; ConcordanceBloqueig de branca; ConcordançaBloqueo de rama; ConcordanciaBACKGROUND: Right bundle branch block is one of the most common electrocardiographic abnormalities. Most cases of right bundle branch block are detected in asymptomatic patients in primary care, so a correct interpretation of electrocardiograms (ECGs) at this level is necessary. The objective of this research is to determine the degree of concordance in the diagnosis of incomplete and complete right bundle branch block between four primary care researchers and a cardiologist. METHODS: The research design is a retrospective cohort study of patients over 18 years of ages of patients over 18 years of ages who underwent an ECG for any reason and were diagnosed with right bundle branch block by their physician. The physicians participating, 4 primary care researchers and a cardiologist were specialized in interpreting electrocardiographic records. The diagnosis of incomplete and complete right bundle branch block was recorded and other secondary variables were analysed. In case of diagnostic discordance between the researchers, the ECGs were reviewed by an expert cardiologist, who interpreted them, established the diagnosis and analysed the possible causes for the discrepancy. RESULTS: We studied 160 patients diagnosed with right bundle branch block by their general practise. The patients had a mean age of 64.8 years and 54% of them were men. The concordance in the diagnosis of incomplete right bundle branch block showed a Fleiss' kappa index (k) of 0.71 among the five researchers and of 0.85 among only the primary care researchers. The k for complete right bundle branch block was 0.93 among the five researchers and 0.96 among only the primary care researchers. CONCLUSION: The interobserver agreement in the diagnosis of right bundle branch block performed by physicians specialized in ECG interpretation (primary care physicians and a cardiologist) was very good. The variability was greater for the diagnosis of incomplete right bundle branch block

Free-electron Model for Mesoscopic Force Fluctuations in Nanowires

When two metal electrodes are separated, a nanometer sized wire (nanowire) is formed just before the contact breaks. The electrical conduction measured during this retraction process shows signs of quantized conductance in units of G_0=2e^2/h. Recent experiments show that the force acting on the wire during separation fluctuates, which has been interpreted as being due to atomic rearrangements. In this report we use a simple free electron model, for two simple geometries, and show that the electronic contribution to the force fluctuations is comparable to the experimentally found values, about 2 nN.Comment: 4 pages, 3 figures, reference correcte

RNAi screens for Rho GTPase regulators of cell shape and YAP/TAZ localisation in triple negative breast cancer.

In order to metastasise, triple negative breast cancer (TNBC) must make dynamic changes in cell shape. The shape of all eukaryotic cells is regulated by Rho Guanine Nucleotide Exchange Factors (RhoGEFs), which activate Rho-family GTPases in response to mechanical and informational cues. In contrast, Rho GTPase-activating proteins (RhoGAPs) inhibit Rho GTPases. However, which RhoGEFs and RhoGAPS couple TNBC cell shape to changes in their environment is very poorly understood. Moreover, whether the activity of particular RhoGEFs and RhoGAPs become dysregulated as cells evolve the ability to metastasise is not clear. Towards the ultimate goal of identifying RhoGEFs and RhoGAPs that are essential for TNBC metastasis, we performed an RNAi screen to isolate RhoGEFs and RhoGAPs that contribute to the morphogenesis of the highly metastatic TNBC cell line LM2, and its less-metastatic parental cell line MDA-MB-231. For ~6 million cells from each cell line, we measured 127 different features following the depletion of 142 genes. Using a linear classifier scheme we also describe the morphological heterogeneity of each gene-depleted population

Mediterranean springs: Keystone ecosystems and biodiversity refugia threatened by global change

Mediterranean spring ecosystems are unique habitats at the interface between surface water and groundwater. These ecosystems support a remarkable array of biodiversity and provide important ecological functions and ecosystem services. Spring ecosystems are influenced by abiotic, biotic, and anthropogenic factors such as the lithology of their draining aquifers, their climate, and the land use of their recharge area, all of which affect the water chemistry of the aquifer and the spring discharges. One of the most relevant characteristics of spring ecosystems is the temporal stability of environmental conditions, including physicochemical features of the spring water, across seasons and years. This stability allows a wide range of species to benefit from these ecosystems (particularly during dry periods), fostering an unusually high number of endemic species. However, global change poses important threats to these freshwater ecosystems. Changes in temperature, evapotranspiration, and precipitation patterns can alter the water balance and chemistry of spring water. Eutrophication due to agricultural practices and emergent pollutants, such as pharmaceuticals, personal care products, and pesticides, is also a growing concern for the preservation of spring biodiversity. Here, we provide a synthesis of the main characteristics and functioning of Mediterranean spring ecosystems. We then describe their ecological value and biodiversity patterns and highlight the main risks these ecosystems face. Moreover, we identify existing knowledge gaps to guide future research in order to fully uncover the hidden biodiversity within these habitats and understand the main drivers that govern them. Finally, we provide a brief summary of recommended actions that should be taken to effectively manage and preserve Mediterranean spring ecosystems for future generations. Even though studies on Mediterranean spring ecosystems are still scarce, our review shows there are sufficient data to conclude that their future viability as functional ecosystems is under severe threat.Mediterranean spring ecosystems are unique habitats supporting a remarkable array of biodiversity and providing important ecological functions and ecosystem services. However, global change poses important threats to these freshwater ecosystems, such as changes in climate patterns and increasing human pressures like overexploitation and pollution. We provide a synthesis of the main characteristics and functioning of Mediterranean spring ecosystems and their threats due to global change.imag

Are environmental factors for atopic eczema in ISAAC Phase Three due to reverse causation?

Some previously described environmental associations for atopic eczema (AE) may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level results for multiple AE risk factors. ISAAC Phase Three surveyed children within schools (the sampling unit) on AE symptoms and potential risk factors. We assessed the effect of these risk factors on AE symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence. 546,348 children from 53 countries were included. At age 6-7 the strongest individual-level associations were with current paracetamol use (odds ratio=1.45, 95% confidence interval 1.37-1.54), which persisted at school-level (1.55, 1.10-2.21), antibiotics (1.41, 1.34-1.48) and early life paracetamol use (1.28, 1.21-1.36) with the former persisting at school-level while the latter was no longer observed (1.35, 1.00-1.82 and 0.94, 0.69-1.28 respectively). At age 13-14 the strongest associations at individual-level were with current paracetamol use (1.57, 1.51-1.63) and open-fire cooking (1.46, 1.33-1.62); both were stronger at school-level (2.57, 1.84-3.59 and 2.38, 1.52-3.73 respectively). Association with exposure to heavy traffic (1.31, 1.27-1.36) also persisted at school-level (1.40, 1.07-1.82). Most individual- and school level effects were consistent tending to exclude reverse causation

Are environmental factors for atopic eczema in ISAAC Phase Three due to reverse causation?

Some previously described environmental associations for atopic eczema (AE) may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level results for multiple AE risk factors. ISAAC Phase Three surveyed children within schools (the sampling unit) on AE symptoms and potential risk factors. We assessed the effect of these risk factors on AE symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence. 546,348 children from 53 countries were included. At age 6-7 the strongest individual-level associations were with current paracetamol use (odds ratio=1.45, 95% confidence interval 1.37-1.54), which persisted at school-level (1.55, 1.10-2.21), antibiotics (1.41, 1.34-1.48) and early life paracetamol use (1.28, 1.21-1.36) with the former persisting at school-level while the latter was no longer observed (1.35, 1.00-1.82 and 0.94, 0.69-1.28 respectively). At age 13-14 the strongest associations at individual-level were with current paracetamol use (1.57, 1.51-1.63) and open-fire cooking (1.46, 1.33-1.62); both were stronger at school-level (2.57, 1.84-3.59 and 2.38, 1.52-3.73 respectively). Association with exposure to heavy traffic (1.31, 1.27-1.36) also persisted at school-level (1.40, 1.07-1.82). Most individual- and school level effects were consistent tending to exclude reverse causation

Structure of the mantle beneath the Alboran Basin from Magnetotelluric Soundings

We present results of marine MT acquisition in the Alboran sea that also incorporates previously acquired land MT from southern Spain into our analysis. The marine data show complex MT response functions with strong distortion due to seafloor topography and the coastline, but inclusion of high resolution topography and bathymetry and a seismically defined sediment unit into a 3‐D inversion model has allowed us to image the structure in the underlying mantle. The resulting resistivity model is broadly consistent with a geodynamic scenario that includes subduction of an eastward trending plate beneath Gibraltar, which plunges nearly vertically beneath the Alboran. Our model contains three primary features of interest: a resistive body beneath the central Alboran, which extends to a depth of ∼150 km. At this depth, the mantle resistivity decreases to values of ∼100 Ohm‐m, slightly higher than those seen in typical asthenosphere at the same depth. This transition suggests a change in slab properties with depth, perhaps reflecting a change in the nature of the seafloor subducted in the past. Two conductive features in our model suggest the presence of fluids released by the subducting slab or a small amount of partial melt in the upper mantle (or both). Of these, the one in the center of the Alboran basin, in the uppermost‐mantle (20-30 km depth) beneath Neogene volcanics and west of the termination of the Nekkor Fault, is consistent with geochemical models, which infer highly thinned lithosphere and shallow melting in order to explain the petrology of seafloor volcanics

EP05.02-003 Durvalumab after Chemoradiotherapy (CRT) in Unresectable Stage III NSCLC. Comparative Study of Two Cohorts in the Real-World Setting

[EN] Introduction: Durvalumab is the new standard of care for unresectable locally advanced NSCLC, with PD-L1 _1% and who did not have progression after CRT treatment in the European Union. Our study compares the effectiveness and the frequency of radiation pneumonitis in patients treated with concurrent CRT with or without durvalumab consolidation during the same period in real clinical practice. Methods: A single-center retrospective study. 71 treated patients with unresectable stage III NSCLC were included between March 2018 and December 2021, 37 with CRT followed by durvalumab and 34 with CRT alone. Real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were calculated since the date of the end CRT. Propensity score matching (PSM) 1:1 was used to account for differences in baseline characteristics. Results: Median age was 67 years (range 46-82). 25.4% of the patients were _75 years old. 78.9% were men and 53.5% former smokers. 54.9% had squamous histology and 28%, 51% and 21% stage IIIA, IIIB and IIIC disease, respectively. The most used scheme was carboplatinpaclitaxel (43.7%), receiving induction chemotherapy in up to 54.9% of patients. 73.2% received between 60-66 Gy doses of radiotherapy. Median time from end of CRT to onset durvalumab was 44 days (range 13-120) with a median of 14 infusions (range 6-27). Of the 34 patients without durvalumab treatment, the expression PD-L1 <1% (58.8%) was the most frequent cause for rejecting consolidation therapy. After PSM analysis, patients distributions were well balanced. With a median follow-up of 19.7 months (range 1.4-36.6); median rw-PFS was 9.3 months (95% CI, 5-13.5) without durvalumab and 17 months (95% CI, 11-22.9) with durvalumab (p¼0.013). Median rw-OS was 19.3 months (95% CI, 3.8-34.8) without durvalumab and 29.9 months (95% CI, 23.3-36.6) with durvalumab (p¼0.241) with a rw-OS% at 6, 18 and 24 months of 90%, 62% and 49% vs 100%, 86% and 74%, respectively. The rate of radiation pneumonitis was more frequent with durvalumab consolidation (56.8% against 44.1%), (p¼0.346), especially within 3 months after CRT. G3 pneumonitis was only observed in the consolidation therapy. Conclusions: Our results demonstrate the effectiveness of durvalumab consolidation after CRT in real-world patients with unresectable stage III NSCLC. Further sample and longer follow-up are required to obtain more accurate results. Active surveillance and appropriate management for radiation pneumonitis are needed, in especially in candidates for consolidation treatmentS