Nanoscale intermittent contact-scanning electrochemical microscopy

A major theme in scanning electrochemical microscopy (SECM) is a methodology for nanoscale imaging with distance control and positional feedback of the tip. We report the expansion of intermittent contact (IC)-SECM to the nanoscale, using disk-type Pt nanoelectrodes prepared using the laser-puller sealing method. The Pt was exposed using a focused ion beam milling procedure to cut the end of the electrode to a well-defined glass sheath radius, which could also be used to reshape the tips to reduce the size of the glass sheath. This produced nanoelectrodes that were slightly recessed, which was optimal for IC-SECM on the nanoscale, as it served to protect the active part of the tip. A combination of finite element method simulations, steady-state voltammetry and scanning electron microscopy for the measurement of critical dimensions, was used to estimate Pt recession depth. With this knowledge, the tip-substrate alignment could be further estimated by tip approach curve measurements. IC-SECM has been implemented by using a piezo-bender actuator for the detection of damping of the oscillation amplitude of the tip, when IC occurs, which was used as a tip-position feedback mechanism. The piezo-bender actuator improves significantly on the performance of our previous setup for IC-SECM, as the force acting on the sample due to the tip is greatly reduced, allowing studies with more delicate tips. The capability of IC-SECM is illustrated with studies of a model electrode (metal/glass) substrate

Spatial heterogeneity enhances and modulates excitability in a mathematical model of the myometrium

The muscular layer of the uterus (myometrium) undergoes profound changes in global excitability prior to parturition. Here, a mathematical model of the myocyte network is developed to investigate the hypothesis that spatial heterogeneity is essential to the transition from local to global excitation which the myometrium undergoes just prior to birth. Each myometrial smooth muscle cell is represented by an element with FitzHugh–Nagumo dynamics. The cells are coupled through resistors that represent gap junctions. Spatial heterogeneity is introduced by means of stochastic variation in coupling strengths, with parameters derived from physiological data. Numerical simulations indicate that even modest increases in the heterogeneity of the system can amplify the ability of locally applied stimuli to elicit global excitation. Moreover, in networks driven by a pacemaker cell, global oscillations of excitation are impeded in fully connected and strongly coupled networks. The ability of a locally stimulated cell or pacemaker cell to excite the network is shown to be strongly dependent on the local spatial correlation structure of the couplings. In summary, spatial heterogeneity is a key factor in enhancing and modulating global excitability

Variational study of two-nucleon systems with lattice QCD

The low-energy spectrum and scattering of two-nucleon systems are studied with lattice quantum chromodynamics using a variational approach. A wide range of interpolating operators are used: dibaryon operators built from products of plane-wave nucleons, hexaquark operators built from six localized quarks, and quasilocal operators inspired by two-nucleon bound-state wave functions in low-energy effective theories. Sparsening techniques are used to compute the timeslice-to-all quark propagators required to form correlation-function matrices using products of these operators. Projection of these matrices onto irreducible representations of the cubic group, including spin-orbit coupling, is detailed. Variational methods are applied to constrain the low-energy spectra of two-nucleon systems in a single finite volume with quark masses corresponding to a pion mass of 806 MeV. Results for S- and D-wave phase shifts in the isospin singlet and triplet channels are obtained under the assumption that partial-wave mixing is negligible. Tests of interpolating-operator dependence are used to investigate the reliability of the energy spectra obtained and highlight both the strengths and weaknesses of variational methods. These studies and comparisons to previous studies using the same gauge-field ensemble demonstrate that interpolating-operator dependence can lead to significant effects on the two-nucleon energy spectra obtained using both variational and nonvariational methods, including missing energy levels and other discrepancies. While this study is inconclusive regarding the presence of two-nucleon bound states at this quark mass, it provides robust upper bounds on two-nucleon energy levels that can be improved in future calculations using additional interpolating operators and is therefore a step toward reliable nuclear spectroscopy from the underlying Standard Model of particle physics

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

PurposeImmune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).Patients and methodsWe performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.ResultsThirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.ConclusionsIpilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

To facilitate access to satellite data: THEIA Land Data Centre

International audienc

Mapping tillage operations over a peri-urban region using combined SPOT4 and ASAR/ENVISAT images

This study aimed at assessing the potential of combining synchronous SPOT4 and ENVISAT/ASAR images (HH and HV polarizations) for mapping tillage operations (TOs) of bare agricultural fields over a peri-urban area characterized by conventional tillage system in the western suburbs of Paris (France). The reference spatial units for spatial modeling are 57 within-field areas named "reference zones" (RZs) homogeneous for their soil properties, constructed in the vicinity of 57 roughness measurement locations, spread across 20 agricultural fields for which TOs were known. The total RZ dataset was half dedicated to successive random selections of training/validating RZs, the remaining half (29 RZs) being kept for validating the final map results. Five supervised per-pixels classifiers were used in order to map 2 TOs classes (seedbed&harrowed and late winter plough) in addition to 4 landuse classes (forest, urban, crops and grass, water bodies): support vector machine with polynomial kernel (pSVM), SVM with radial basis kernel (rSVM), artificial neural network (ANN), Maximum Likelihood (ML), and regression tree (RT). All 5 classifiers were implemented in a bootstrapping approach in order to assess the uncertainty of map results. The best results were obtained with pSVM for the SPOT4/ASAR pair with producer's and user's mean validation accuracies (PmVA/UmVA) of 91.7%/89.8% and 73.2%/73.3% for seedbed&harrowed and late winter plough conditions, respectively. Whatever classifier, the SPOT4/ASAR pair appeared to perform better than each of the single images, particularly for late winter plough: PmVA/UmVA of 61.6%/53.0% for the single SPOT4 image; 0%/6% for the single ASAR image. About 73% of the validation agricultural fields (79% of the RZs) were correctly predicted in terms of TOs in the best pSVM-derived final map. Final map results could be improved through masking non-agricultural areas with land use identification system layer prior to classifying images. Such knowledge of agricultural operations is likely to facilitate the mapping of agricultural systems which otherwise proceed from time-consuming surveys to farmers

Key Attack Strategies Against Black-Box DNNs

International audienceIn this paper, we examined to what extent and under what settings the confidentiality and integrity of black-box DNNs—which are the most challenging setup of DNNs—can be threatened. In this way, we proposed a comprehensive taxonomy of the key strategies developed in the literature to attack black-box DNNs.We believe that a coherent classification incorporating all key aspects is needed to organise the body of knowledge on research and methodologies for understanding and securing black-box DNNs

Key Attack Strategies Against Black-Box DNNs

International audienceIn this paper, we examined to what extent and under what settings the confidentiality and integrity of black-box DNNs—which are the most challenging setup of DNNs—can be threatened. In this way, we proposed a comprehensive taxonomy of the key strategies developed in the literature to attack black-box DNNs.We believe that a coherent classification incorporating all key aspects is needed to organise the body of knowledge on research and methodologies for understanding and securing black-box DNNs

Key Attack Strategies Against Black-Box DNNs

International audienceIn this paper, we examined to what extent and under what settings the confidentiality and integrity of black-box DNNs—which are the most challenging setup of DNNs—can be threatened. In this way, we proposed a comprehensive taxonomy of the key strategies developed in the literature to attack black-box DNNs.We believe that a coherent classification incorporating all key aspects is needed to organise the body of knowledge on research and methodologies for understanding and securing black-box DNNs