Interdigitated ring electrodes: Theory and experiment

The oxidation of potassium ferrocyanide, K_4Fe(CN)_6, in aqueous solution under fully supported conditions is carried out at interdigitated band and ring electrode arrays, and compared to theoretical models developed to simulate the processes. Simulated data is found to fit well with experimental results using literature values of diffusion coefficients for Fe(CN)_6^(4-) and Fe(CN)_6^(3-). The theoretical models are used to compare responses from interdigitated band and ring arrays, and the size of ring array required to approximate the response to a linear band array is investigated. An equation is developed for the radius of ring required for a pair of electrodes in a ring array to give a result with 5% of a pair of electrodes in a band array. This equation is found to be independent of the scan rate used over six orders of magnitude

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

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

Inversion of multi-mode Rayleigh wave dispersion curves for regional imaging: Application to the Basque-Cantabrian Zone (N Spain)

AGU Fall Meeting 2019, in San Francisco, 9-13 december 2019Surface waves in seismic noise correlation functions are routinely exploited to image structures at a broad range of scales and resolutions. In most applications, the correlation functions are considered (1) to be estimates of the Green¿s function between pairs of receivers and (2) to be composed mainly of fundamental-mode surface waves. This approach requires at least an inter-station distance of 3 wavelengths to produce reliable phase/group velocity measurements, which can be a limiting factor when working at local or regional scales. Additionally, as shown by many previous studies, the presence of superficial low-velocity layers may cause a dominance of higher modes over certain frequency ranges, which means that only considering the fundamental mode may not be enough to accurately model the observed dispersion curves. In this work, we overcome the limitations by measuring Rayleigh wave phase velocities directly from the cross-correlation spectra. This approach does not depend on the far-field approximation and is, therefore, not subject to the three-wavelength rule. We use these measurements to produce a set of phase velocity maps using a standard tomographic algorithm. Finally, for a set of regularly spaced nodes, dispersion curves are compiled from the phase velocity maps and used in a non-linear inversion to obtain the 1D shear-wave velocity structure. Previous geological and geophysical studies are used to place constraints on the non-linear inversion. We apply this methodology to seismic data acquired in the Basque-Cantabrian region (N Spain) between 2014 and 2018 (by the SISCAN-MISTERIOS network, with inter-station distances ranging from 7 to 400 km) and obtain a 3D model of this structurally complex area (a thick Mesozoic basin inverted and incorporated into the Pyrenean-Cantabrian mountain belt in the Cenozoic) which agrees with the existing geological knowledge but significantly extends the area for which high-resolution information is available

Joint inversion of multiple mode Rayleigh wave dispersion curves and H/V spectral ratios measured from ambient noise: application to the Basque-Cantabrian Basin (N of Spain)

EGU General Assembly 2019, in Viena, Austria, 7–12 April 2019Many ambient noise tomography applications are based on measuring surface wave group velocities from timedomain cross-correlations. This approach has several downsides, among them being: (A) reliable group velocity measurements require at least an inter-station distance of 3 wavelengths, (B) usually, only the fundamental mode of Rayleigh wave propagation is considered, disregarding the possible contribution to the observed group/phase velocity of higher modes, and (C) surface wave dispersion measurements only offer weak constraints for the very shallow and the very deep shear-wave velocity structure at the periods used in most regional studies. To overcome these limitations, we propose an inversion scheme based on Aki’s spectral formulation. First, we measured Rayleigh wave phase velocities by fitting Bessel functions to the observed cross-correlation spectra, and used these measurements in a tomographic inversion to produce a set of phase velocity maps. Then, we defined a grid of regularly spaced nodes on the phase velocity maps, and used the dispersion information on a non-linear inversion to obtain a 1D shear-wave velocity profile at each node. Our inversion scheme considers the influence of higher modes in the observed phase velocities. The same noise recordings used for measuring surface wave dispersion can be used to determine the H/V spectral ratios at the receivers. The fundamental frequency and the shape of the peaks in the H/V ratios can be related to the thickness of the sediment layers and the impedance contrasts between the sediments and the basement, thus providing additional constraints for the deep shear-wave velocity structure in the vicinity of the receivers. Therefore, for the nodes closer to the receivers, we performed a joint inversion of the Rayleigh wave phase velocities and the H/V spectral ratios. We applied this methodology to the data provided by the SISCAN-MISTERIOS network, a regularlyspaced grid of 40 broad-band stations with inter-station distances ranging from 27 to 440 km, deployed in the Basque-Cantabrian basin (N Spain) during the period 2014-2018. The Basque-Cantabrian basin (N Spain) is one of the major Mesozoic extensional basins developed during the opening of the Bay of Biscay. In Cenozoic times, the Alpine collision between the European plate and Iberian sub-plate caused the inversion of the normal faults, the reactivation of older (Variscan) thrusts and the creation of new structures. As a consequence, both the depth to the Paleozoic basement and the velocity structure vary greatly across the area, providing a challenging scenario to test the proposed methodology. In spite of some difficulties (i.e. weak impedance contrasts between the Mesozoic sediments and the Paleozoic basement in parts of the basin, problems to retrieve accurate spectral ratios for some stations at the considered frequencies, etc), the application of the methodology described above provided good results in areas where the structure was known in detail, and allowed us to achieve a better constrained image of the 3D shear-wave velocity structure across the whole basin

Seismic tomography in the Basque-Cantabrian basin: Rayleigh wave phase velocities, Vp, Vs and Vp/Vs determined from ambient noise and local events across the SISCAN seismic network

The Basque-Cantabrian basin, located in the north of Spain, represents the main Mesozoic extensional basin developed during the opening of de Bay of Biscay. This basin shows a very high subsidence with sediment thickness exceeding 20 km. In Cenozoic times, it was inverted as part of the Pyrenean-Cantabrian Mountains. The SISCAN seismic network was designed to high-resolution long-term monitoring of the seismic activity within the basin and to gain insight into basement depth of sedimentary basin and its crustal structure by the use of different tomographic techniques. The network consists of 31 broad-band seismic stations with a mean inter-station distance of 30 km. Its deployment concluded in July 2014 and it is operative since then. The geometry and close spacing of the SISCAN network coupled with the relatively weak but persistent regional seismicity favor the application of both ambient noise and body wave local tomography techniques. Since time domain methods suffer from limitations at short inter-station distances, Rayleigh wave phase velocities have been measured from the cross-correlation spectrum of the continuous records provided by the network. These measurements have been used in a tomographic inversion to produce a set of preliminary phase velocity maps for periods ranging from 5 to 20 s. In addition, more than 12000 P-wave travel times and near 8000 S-wave travel times from about 1500 events recorded in 3 years were inverted to obtain the three-dimensional velocity structure of the area for P-waves, S-waves and the Vp/Vs ratio. Preliminary results reflect a significant agreement between the outcomes of both methods (considering their different approaches and resolutions) and with the existing geological knowledge of the basin. Low phase velocities are recovered for the zones with a thicker sedimentary cover (like the Villarcayo and Miranda-Treviño synclines, and the western end of the Jaca-Pamplona basin) and along the Pamplona transfer fault. Relatively high velocities are found in areas where the Paleozoic basement crops out or lies at shallow depths within the basin. More quantitative results will arise from future lines of work including a rigorous assessment of the uncertainties and the refinement of the inversion procedures.Peer Reviewe

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease

The DUNE Far Detector Vertical Drift Technology, Technical Design Report

International audienceDUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals

The DUNE Far Detector Vertical Drift Technology, Technical Design Report

International audienceDUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals