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Abstract We investigate electric dipole spin resonance (EDSR) induced by an oscillating electric field within a system of double quantum dots formed electrostatically in monolayer phosphorene. Apart from the observed anisotropy of effective masses, phosphorene has been predicted to exhibit anisotropic spin-orbit coupling. Here, we examine a system consisting of two electrons confined in double quantum dots. A single-band effective Hamiltonian together with the configuration interaction theory is implemented to simulate the time evolution of the ground state. We examine spin flips resulting from singlet-triplet transitions driven by external AC electric fields, both near and away from the Pauli blockade regime, revealing fast sub-nanosecond transition times. Furthermore, we analyze the impact of anisotropy by comparing dots arranged along a different crystal axis. The sub-harmonic multi-photon transitions and Landau-Zener-Stückelberg-Majorana transitions are discussed. We show modulation of spin-like and charge-like characteristics of the qubit through potential detuning.

Geoffrey Bloy,1 Amelie Jurine,1 Yann Chaussy,2 Frederic Auber,2 Pierre-Gregoire Guinot,3 Belaid Bouhemad,3 Michel Francois,4 Lucie Vettoretti,1 Sebastien Pili-Floury,5 Maxime Nguyen,3 Guillaume Besch5 1CHU Besançon, Département d’Anesthésie Réanimation Chirurgicale, Besançon, F-25000, France; 2Université de Franche-Comté, CHU Besançon, SINERGIES, Service de Chirurgie Pédiatrique, Besançon, F-25000, France; 3University of Burgundy and Franche-Comté, Dijon University Hospital, INSERM LNC UMR1231, FCS Bourgogne Franche-Comté LipSTIC LabEx, Dijon, F-21000, France; 4Université de Bourgogne, CHU Dijon, Service de Chirurgie Pédiatrique, Dijon, F-21000, France; 5Université de Franche-Comté, CHU Besançon, SINERGIES, Département d’Anesthésie Réanimation Chirurgicale, Besançon, F-25000, FranceCorrespondence: Guillaume Besch, Département d’Anesthésie Réanimation Chirurgicale, CHU Besançon, 3 bvd Alexandre Fleming, Besançon, 25030, France, Tel +3381218958, Fax +3381669331, Email gbesch@chu-besancon.frPurpose: Postoperative pain relief after laparoscopic appendicectomy is a key determinant of early rehabilitation in children. Recent guidelines recommend performing either a transversus abdominis plane (TAP) block or local anesthesia (LA) wound infiltration as part of multimodal postoperative analgesia after appendectomy. To date, the clinical effectiveness of TAP block versus LA wound infiltration has never been compared. The hypothesis of this study is that the TAP block may provide a greater opioid-sparing effect after laparoscopic appendicectomy in children than LA wound infiltration.Study Design and Methods: We designed a multicenter double-blind randomized controlled phase III trial and aim to include 110 children who undergo laparoscopic appendicectomy. Children are randomized to receive either TAP block (TAP group) or LA wound infiltration (infiltration group). Multimodal analgesia is standardized in the two groups using the same protocol, which includes the stepwise prescription of paracetamol, phloroglucinol, ketoprofene, and nalbuphine according to the hetero-evaluation of pain performed by the nurses who were blinded to the treatment allocated using the validated FLACC scale. The primary outcome is the total dose of nalbuphine administered within 24 hours after surgery.Discussion: No study has specifically compared the clinical effectiveness of TAP block versus LA wound infiltration for postoperative pain relief after laparoscopic appendectomy in children. This paper describes the protocol for a randomized trial that addresses this issue. The results of this trial will be useful for editing guidelines with a higher level of evidence on this topic.Keywords: laparoscopic appendectomy, TAP block, wound infiltration, analgesia, children

2D nanoporous membranes are predicted to provide highly selective gas transport in combination with extreme permeance. Here authors demonstrate gas separation performance and transport mechanisms through membranes of graphdiyne, a quasi 2D material with a graphene-like structure.

Abstract Despite substantial efforts to control locusts they remain periodically a major burden in Africa, causing severe yield loss and hence loss of food and income. Distribution maps indicating the value of the basic reproduction number R 0 was used to identify areas where an insect pest can be controlled by a natural enemy. A dynamic process-based mathematical model integrating essential features of a natural enemy and its interaction with the pest is used to generate R 0 risk maps for insect pest outbreaks, using desert locust and the entomopathogenic fungus Metarhizium acridum (Synn. Metarhizium anisoliae var. acridum) as a case study. This approach provides a tool for evaluating the impact of climatic variables such as temperature and relative humidity and mapping spatial variability on the efficacy of M. acridum as a biocontrol agent against desert locust invasion in Africa. Applications of M. acridum against desert locust in a few selected African countries including Morocco, Kenya, Mali, and Mauritania through monthly spatial projection of R 0 maps for the prevailing climatic condition are illustrated. By combining mathematical modeling with a geographic information system in a spatiotemporal projection as we do in this study, the field implementation of microbial control against locust in an integrated pest management system may be improved. Finally, the practical utility of this model provides insights that may improve the timing of pesticide application in a selected area where efficacy is highly expected.

Only a minority of patients with glioblastoma (GBM) respond to immunotherapy, and always only partially. There is a lack of knowledge on immune distribution in GBM and in its tumor microenvironment (TME). To address the question, we used paired primary and recurrent tumors from GBM patients to study the composition and the evolution of the immune landscape upon treatment. We studied the expression of a handful of immune markers (CD3, CD8, CD68, PD-L1 and PD-1) in GBM tissues in 15 paired primary and recurrent GBM. In five selected patients, we used Nanostring Digital Spatial Profiling (DSP) to obtain simultaneous assessments of multiple biomarkers both within the tumor and the microenvironment in paired primary and recurrent GBM. Our results suggest that the evolution of the immune landscape between paired primary and recurrent GBM tumors is highly heterogeneous. However, our study identifies B3-H7 and HLA-DR as potential targets in primary and recurrent GBM. Spatial profiling of immune markers from matched primary and recurrent GBM shows a nonlinear complex evolution during the progression of cancer. Nonetheless, our study demonstrated a global increase in macrophages, and revealed differential localization of some markers, such as B7-H3 and HLA-DR, between GBM and its TME.

A superconducting diode is dissipationless and desirable for electronic circuits with ultralow power consumption, yet it remains challenging to realize it. Here, the authors achieve a superconducting diode in a conventional superconducting film patterned with a conformal array of nanoscale holes.

The paper describes a case study on the design of district energy infrastructure for the green-field project of the Vale de Santo António (Lisbon, Portugal). The methodology is based on a novel framework built on the sequential integration of three software tools: QGIS, City Energy Analyst (CEA) and Urbio. QGIS is used to define the building database (construction solutions, uses and schedules); CEA is used to model the neighborhood energy services (heating, cooling, domestic hot water and electricity, including for EVs); and Urbio is used to design the energy infrastructure to supply the neighborhood in an optimal manner. The study illustrates the high impact of building renovation on heat demand and the existing potential for a two-layout network to minimize pumping demand and heat distribution loss. Moreover, a sensitivity analysis with regard to future carbon tax changes and electricity greening concludes that an electricity-based heating mix is optimal.

Hypertension is regulated by immunological components. Spontaneously hypertensive rats (SHR) display a large population of proinflammatory CD161 + immune cells. We investigated the effect of early post-natal gut microbiota on the development of the immune system and resulting hypertension in the SHR. We first examined the microbial populations in the fecal samples of SHR and normotensive control WKY using 16S rDNA sequencing. We found that in the newborn SHR (1-week old) the gut microbiota was qualitatively and quantitatively different from the newborns of normotensive WKY. The representation of the predominant bacterial phylum Proteobacteria was significantly less in 1-week old SHR pups than in WKY (94.5% Proteobacteria in WKY vs. 65.2% in SHR neonates). Even within the phylum Proteobacteria, the colonizing genera in WKY and SHR differed dramatically. Whereas WKY microbiota was predominantly comprised of Escherichia-Shigella, SHR microbiota was represented by other taxa of Enterobacteriaceae and Pasteurellaceae. In contrast, the representation of phylum Firmicutes in the neonatal SHR gut was greater than WKY. Cross-fostering newborn SHR pups by lactating WKY dams caused a dramatic shift in 1-week old cross-fostered SHR gut microbiota. The two major bacterial taxa of phylum Proteobacteria, Enterobacteriaceae and Pasteurellaceae as well as Lactobacillus intestinalis, Proteus, Romboustia and Rothia were depleted after cross-fostering and were replaced by the predominant genera of WKY (Escherichia-Shigella). A proinflammatory IL-17F producing CD161 + immune cell population in the spleen and aorta of cross-fostered SHR was also reduced (30.7% in self-fostered SHR vs. 12.6% in cross-fostered SHR at 30 weeks of age) as was the systolic blood pressure in adult cross-fostered SHR at 10 weeks of age. Thus, altered composition of gut microbiota of SHR toward WKY at early neonatal age had a long-lasting effect on immune system by reducing proinflammatory immune cells and lowering systolic blood pressure.

Polyadenylation stabilizes edited mitochondrial mRNAs in Trypanosoma brucei, but the involved poly(A) binding protein is unknown. Here, Mesitov et al. show that a pentatricopeptide repeat factor KPAF4 binds to A-tail and prevents exonucleolytic degradation as well as translation of incompletely edited mRNAs.

Introduction Despite the high prevalence of obstructive sleep apnoea (OSA) in obese patients undergoing bariatric surgery, OSA is undiagnosed in the majority of patients and thus untreated. While untreated OSA is associated with an increased risk of preoperative and postoperative complications, no evidence-based guidelines on perioperative care for these patients are available. The aim of the POPCORN study (Post-Operative Pulse oximetry without OSA sCreening vs perioperative continuous positive airway pressure (CPAP) treatment following OSA scReeNing by polygraphy (PG)) is to evaluate which perioperative strategy is the most cost-effective for obese patients undergoing bariatric surgery without a history of OSA.Methods and analysis In this multicentre observational cohort study, data from 1380 patients who will undergo bariatric surgery will be collected. Patients will receive either postoperative care with pulse oximetry monitoring and supplemental oxygen during the first postoperative night, or care that includes preoperative PG and CPAP treatment in case of moderate or severe OSA. Local protocols for perioperative care in each participating hospital will determine into which cohort a patient is placed. The primary outcome is cost-effectiveness, which will be calculated by comparing all healthcare costs with the quality-adjusted life-years (QALYs, calculated using EQ-5D questionnaires). Secondary outcomes are mortality, complications within 30 days after surgery, readmissions, reoperations, length of stay, weight loss, generic quality of life (QOL), OSA-specific QOL, OSA symptoms and CPAP adherence. Patients will receive questionnaires before surgery and 1, 3, 6 and 12 months after surgery to report QALYs and other patient-reported outcomes.Ethics and dissemination Approval from the Medical Research Ethics Committees United was granted in accordance with the Dutch law for Medical Research Involving Human Subjects Act (WMO) (reference number W17.050). Results will be submitted for publication in peer-reviewed journals and presented at (inter)national conferences.Trial registration number NTR6991.

Cardiovascular disease (CVD) risk in type 2 diabetes mellitus (T2DM) increases with the development of albuminuria and is related in part to dyslipidemia. The present analysis assessed lipid profile and patterns of dyslipidemia in T2DM patients according to albuminuria status. This was a post hoc analysis of data from 181 T2DM patients seen at a tertiary health-care hospital and enrolled in a cross-sectional study of albuminuria status. Abnormal albuminuria was defined as microalbuminuria [albumin to creatinine ratio (ACR) 30-299.9 mg/g] or macro-albuminuria (ACR ≥300 mg/g). Atherogenic dyslipidemia was defined as triglycerides (TGs) ≥150 mg/dL and/or high-density lipoprotein-cholesterol (HDL-c)

Abstract Background Malaria is highly sensitive to climatic variables and is strongly influenced by the presence of vectors in a region that further contribute to parasite development and sustained disease transmission. Mathematical analysis of malaria transmission through the use and application of the value of the basic reproduction number (R0) threshold is an important and useful tool for the understanding of disease patterns. Methods Temperature dependence aspect of R0 obtained from dynamical mathematical network model was used to derive the spatial distribution maps for malaria transmission under different climatic and intervention scenarios. Model validation was conducted using MARA map and the Annual Plasmodium falciparum Entomological Inoculation Rates for Africa. Results The inclusion of the coupling between patches in dynamical model seems to have no effects on the estimate of the optimal temperature (about 25 °C) for malaria transmission. In patches environment, we were able to establish a threshold value (about α = 5) representing the ratio between the migration rates from one patch to another that has no effect on the magnitude of R0. Such findings allow us to limit the production of the spatial distribution map of R0 to a single patch model. Future projections using temperature changes indicated a shift in malaria transmission areas towards the southern and northern areas of Africa and the application of the interventions scenario yielded a considerable reduction in transmission within malaria endemic areas of the continent. Conclusions The approach employed here is a sole study that defined the limits of contemporary malaria transmission, using R0 derived from a dynamical mathematical model. It has offered a unique prospect for measuring the impacts of interventions through simple manipulation of model parameters. Projections at scale provide options to visualize and query the results, when linked to the human population could potentially deliver adequate highlight on the number of individuals at risk of malaria infection across Africa. The findings provide a reasonable basis for understanding the fundamental effects of malaria control and could contribute towards disease elimination, which is considered as a challenge especially in the context of climate change.

Point-of-care diagnostics have the potential to increase diagnosis and linkage to care and help reach the WHO targets to eliminate hepatitis C virus (HCV) by 2030. Here, we evaluated the diagnostic accuracy of Genedrive HCV ID assay for the qualitative detection of HCV RNA in decentralized settings in two low- and middle-income countries using fresh plasma specimens from 426 participants. The Abbott RealTime HCV assay was used as the gold standard. Genedrive HCV ID assay was conducted by different users. Users also completed questionnaires to assess the usability of Genedrive. At detection thresholds of 12 IU/mL or 30 IU/mL, 1000 IU/mL, and 2362 IU/mL, the sensitivity was 96.2% (95% CI: 92.7–98.4), 100% (98.2–100), and 100% (98.2–100), respectively; the specificity was 99.5% (95% CI: 97.4–100), 99.5% (97.5–100), and 98.7% (96.1–100), respectively. All genotypes detected using the gold-standard assay were also detected with Genedrive. Users found Genedrive easy to use. Genedrive is a simple and accurate test to confirm chronic HCV infection in decentralized, real-life, resource-limited settings. This novel diagnostic tool could contribute to closing the current gap in HCV diagnosis.

Abstract A new method has been developed for the isolation of 223,224,225Ra, in high yield and purity, from a proton irradiated 232Th matrix. Herein we report an all-aqueous process using multiple solid-supported adsorption steps including a citrate chelation method developed to remove >99.9% of the barium contaminants by activity from the final radium product. A procedure involving the use of three columns in succession was developed, and the separation of 223,224,225Ra from the thorium matrix was obtained with an overall recovery yield of 91 ± 3%, average radiochemical purity of 99.9%, and production yields that correspond to physical yields based on previously measured excitation functions.

Transition metal trichalcogenides are layered materials with strong in-plane anisotropy, and their vibrational characteristics remain largely unexplored. Here, the authors present high-pressure Raman studies to uncover unusual vibrational effects within this specific class of materials.

The grain scale of materials is an area still open for investigations within the field of materials science. The most helpful tools to perform this type of research are diffraction methods. Within the research project presented in this paper two experiments were carried out employing two different types of radiation: neutron (ISIS) and synchrotron (ESRF). The aim of the work was to describe the stress state in the necking zone during the occurrence of a damage phenomenon (Fig. 1.) in separate phase and to check the level of the homogeneity. The supplemental tools were the finite elements method and self-consistent modeling – it testified, confirmed and completed our experimental results and allowed us to formulate the justifiable conclusions.

In vertebrates, functional motoneurons are defined as differentiated neurons that are connected to a central premotor network and activate peripheral muscle using acetylcholine. Generally, motoneurons and muscles develop simultaneously during embryogenesis. However, during Xenopus metamorphosis, developing limb motoneurons must reach their target muscles through the already established larval cholinergic axial neuromuscular system. Here, we demonstrate that at metamorphosis onset, spinal neurons retrogradely labeled from the emerging hindlimbs initially express neither choline acetyltransferase nor vesicular acetylcholine transporter. Nevertheless, they are positive for the motoneuronal transcription factor Islet1/2 and exhibit intrinsic and axial locomotor-driven electrophysiological activity. Moreover, the early appendicular motoneurons activate developing limb muscles via nicotinic antagonist-resistant, glutamate antagonist-sensitive, neuromuscular synapses. Coincidently, the hindlimb muscles transiently express glutamate, but not nicotinic receptors. Subsequently, both pre- and postsynaptic neuromuscular partners switch definitively to typical cholinergic transmitter signaling. Thus, our results demonstrate a novel context-dependent re-specification of neurotransmitter phenotype during neuromuscular system development.

Case investigation and contact tracing (CICT) were among the primary nonpharmaceutical interventions for COVID-19 before vaccines became widely available. Previous studies estimated that CICT played an important role in mitigating [...]

Steam is a key energy vector for industrial sites, most commonly used for process heating and cooling, cogeneration of heat and mechanical power, as a motive fluid or for stripping. Steam networks are used to carry steam from producers to consumers and between pressure levels through letdowns and steam turbines. The steam producers (boilers, heat and power cogeneration units, heat exchangers, chemical reactors) should be sized to supply the consumers at nominal operating conditions as well as peak demand.This paper firstly proposes an Mixed Integer Linear Programming formulation to optimise the operations of steam networks in normal operating conditions and exceptional demand (when operating reserves fall to zero), through the introduction of load shedding. Optimisation of investments based on operational and investment costs are included in the formulation.Though rare, boiler failures can have a heavy impact of steam network operations and costs, leading to undercapacity and unit shutdowns. A method is therefore proposed to simulate steam network operations when facing boiler failures. Key performance indicators are introduced to quantify the network's resilience.The proposed methods are applied and demonstrated in an industrial case study using industrial data. The results indicate the importance of oversizing key steam producing equipments and the value of industrial symbiosis to increase industrial site resilience.

Studies of behavioral consequences after unilateral labyrinthectomy have a long tradition in the quest of determining rules and limitations of the CNS to exert plastic changes that assist the recuperation from the loss of sensory inputs. Frogs were among the first animal models to illustrate general principles of regenerative capacity and reorganizational neural flexibility after a vestibular lesion. The continuous successful use of the latter animals is in part based on the easy access and identifiability of nerve branches to inner ear organs for surgical intervention, the possibility to employ whole brain preparations for in vitro studies and the limited degree of freedom of postural reflexes for quantification of behavioral impairments and subsequent improvements. Major discoveries that increased the knowledge of post-lesional reactive mechanisms in the central nervous system include alterations in vestibular commissural signal processing and activation of cooperative changes in excitatory and inhibitory inputs to disfacilitated neurons. Moreover, the observed increase of synaptic efficacy in propriospinal circuits illustrates the importance of limb proprioceptive inputs for postural recovery. Accumulated evidence suggests that the lesion-induced neural plasticity is not a goal-directed process that aims towards a meaningful restoration of vestibular reflexes but rather attempts a survival of those neurons that have lost their excitatory inputs. Accordingly, the reaction mechanism causes an improvement of some components but also a deterioration of other aspects as seen by spatio-temporally inappropriate vestibulo-motor responses, similar to the consequences of plasticity processes in various sensory systems and species. The generality of the findings indicate that frogs continue to form a highly amenable vertebrate model system for exploring molecular and physiological events during cellular and network reorganization after a loss of vestibular function.

The kynurenine pathway (KP) of tryptophan metabolism is linked to antimicrobial activity and modulation of immune responses but its role in stem cell biology is unknown. We show that human and mouse mesenchymal and neural stem cells (MSCs and NSCs) express the complete KP, including indoleamine 2,3 dioxygenase 1 (IDO) and IDO2, that it is highly regulated by type I (IFN-β) and II interferons (IFN-γ), and that its transcriptional modulation depends on the type of interferon, cell type and species. IFN-γ inhibited proliferation and altered human and mouse MSC neural, adipocytic and osteocytic differentiation via the activation of IDO. A functional KP present in MSCs, NSCs and perhaps other stem cell types offers novel therapeutic opportunities for optimisation of stem cell proliferation and differentiation.