Analysis of the accuracy of actuation electronics in the laser interferometer space antenna pathfinder

The Laser Interferometer Space Antenna Pathfinder (LPF) main observable, labeled Δg, is the differential force per unit mass acting on the two test masses under free fall conditions after the contribution of all non-gravitational forces has been compensated. At low frequencies, the differential force is compensated by an applied electrostatic actuation force, which then must be subtracted from the measured acceleration to obtain Δg. Any inaccuracy in the actuation force contaminates the residual acceleration. This study investigates the accuracy of the electrostatic actuation system and its impact on the LPF main observable. It is shown that the inaccuracy is mainly caused by the rounding errors in the waveform processing and also by the random error caused by the analog to digital converter random noise in the control loop. Both errors are one order of magnitude smaller than the resolution of the commanded voltages. We developed a simulator based on the LPF design to compute the close-to-reality actuation voltages and, consequently, the resulting actuation forces. The simulator is applied during post-processing the LPF data

Definition, diagnosis and treatment of oligometastatic oesophagogastric cancer: A Delphi consensus study in Europe

BACKGROUND Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. METHODS In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%). RESULTS A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). CONCLUSION The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials

Emerging topics in nanophononics and elastic, acoustic, and mechanical metamaterials: an overview

This broad review summarizes recent advances and “hot” research topics in nanophononics and elastic, acoustic, and mechanical metamaterials based on results presented by the authors at the EUROMECH 610 Colloquium held on April 25–27, 2022 in Benicássim, Spain. The key goal of the colloquium was to highlight important developments in these areas, particularly new results that emerged during the last two years. This work thus presents a “snapshot” of the state-of-the-art of different nanophononics- and metamaterial-related topics rather than a historical view on these subjects, in contrast to a conventional review article. The introduction of basic definitions for each topic is followed by an outline of design strategies for the media under consideration, recently developed analysis and implementation techniques, and discussions of current challenges and promising applications. This review, while not comprehensive, will be helpful especially for early-career researchers, among others, as it offers a broad view of the current state-of-the-art and highlights some unique and flourishing research in the mentioned fields, providing insight into multiple exciting research directions

Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson’s disease, essential tremor, Alzheimer’s disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year’s international Think Tank, with a view toward current and near future advancement of the field

A worldwide survey on incidence, management, and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study

AIMS Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse. METHODS AND RESULTS This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553 729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed, at 214 centres in 35 countries. In 78 centres 138 patients [0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (P < 0.0001)] were diagnosed with an oesophageal fistula. Peri-procedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8% and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) [odds ratio 7.463 (2.414, 23.072) P < 0.001]. CONCLUSION Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high

EAACI guidelines on the diagnosis of IgE‐mediated food allergy

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE‐mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy‐focused clinical history followed by tests to determine IgE sensitization, such as serum allergen‐specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen‐sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance

CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome

18-month occurrence of severe events among early diagnosed HIV-infected children before antiretroviral therapy in Abidjan, Côte d'Ivoire: A cohort study

<p>Abstract</p> <p>Objective</p> <p>To assess the 18-month field effectiveness on severe events of a pediatric package combining early HIV-diagnosis and targeted cotrimoxazole prophylaxis in HIV-infected children from age six-week before the antiretroviral era, in Abidjan, Côte d'Ivoire.</p> <p>Methods</p> <p>Data from two consecutive prevention of HIV mother-to-child transmission programs were compared: the ANRS 1201/1202 Ditrame-Plus cohort (2001–2005) and the pooled data of the ANRS 049a Ditrame randomized trial and its following open-labeled cohort (1995–2000), used as a reference group. HIV-infected pregnant women ≥ 32–36 weeks of gestation were offered a short-course peri-partum antiretroviral prophylaxis (ZDV in Ditrame, and ZDV ± 3TC+single-dose (sd) NVP in Ditrame-Plus). Neonatal prophylaxis was provided in Ditrame-Plus only: 7-day ZDV and sdNVP 48–72 h after birth. A 6-week pediatric HIV-RNA diagnosis was provided on-line in the Ditrame-Plus while it was only oriented on clinical symptoms in Ditrame. Six-week HIV-infected children received a daily cotrimoxazole prophylaxis in Ditrame-Plus while no prophylaxis was provided in Ditrame. The determinants of severe events (death or hospitalization > 1 day) were assessed in a Cox regression model.</p> <p>Results</p> <p>Between 1995 and 2003, 98 out of the 1121 live-births were diagnosed as HIV-infected in peri-partum: 45 from Ditrame-Plus and 53 from Ditrame. The 18-month Kaplan-Meier cumulative probability of presenting a severe event was 66% in Ditrame-Plus (95% confidence interval [95%CI]: 50%–81%) and 77% in Ditrame (95%CI: 65%–89%), Log Rank test: p = 0.47. After adjustment on maternal WHO clinical stage, maternal death, 6-week pediatric viral load, birth-weight, and breastfeeding exposure, the 18-month risk of severe event was lower in Ditrame-Plus than in Ditrame (adjusted Hazard Ratio (aHR): 0.55, 95%CI: 0.3–1.1), although the difference was not statistically significant; p = 0.07). Maternal death was the only variable determinant of the occurrence of severe events in children (aHR: 3.73; CI: 2.2–11.2; p = 0.01).</p> <p>Conclusion</p> <p>Early cotrimoxazole from 6 weeks of age in HIV-infected infants seemed to reduce probability of severe events but the study lacked statistical power to prove this. Even with systematic cotrimoxazole prophylaxis, infant morbidity and mortality remained high pointing towards a need for early pediatric HIV-diagnosis and antiretroviral treatment in Africa.</p

The Supercam Instrument Suite on the NASA Mars 2020 Rover: Body Unit and Combined System Tests

The SuperCam instrument suite provides the Mars 2020 rover, Perseverance, with a number of versatile remote-sensing techniques that can be used at long distance as well as within the robotic-arm workspace. These include laser-induced breakdown spectroscopy (LIBS), remote time-resolved Raman and luminescence spectroscopies, and visible and infrared (VISIR; separately referred to as VIS and IR) reflectance spectroscopy. A remote micro-imager (RMI) provides high-resolution color context imaging, and a microphone can be used as a stand-alone tool for environmental studies or to determine physical properties of rocks and soils from shock waves of laser-produced plasmas. SuperCam is built in three parts: The mast unit (MU), consisting of the laser, telescope, RMI, IR spectrometer, and associated electronics, is described in a companion paper. The on-board calibration targets are described in another companion paper. Here we describe SuperCam’s body unit (BU) and testing of the integrated instrument. The BU, mounted inside the rover body, receives light from the MU via a 5.8 m optical fiber. The light is split into three wavelength bands by a demultiplexer, and is routed via fiber bundles to three optical spectrometers, two of which (UV and violet; 245–340 and 385–465 nm) are crossed Czerny-Turner reflection spectrometers, nearly identical to their counterparts on ChemCam. The third is a high-efficiency transmission spectrometer containing an optical intensifier capable of gating exposures to 100 ns or longer, with variable delay times relative to the laser pulse. This spectrometer covers 535–853 nm (105–7070 cm−1 Raman shift relative to the 532 nm green laser beam) with 12 cm−1 full-width at half-maximum peak resolution in the Raman fingerprint region. The BU electronics boards interface with the rover and control the instrument, returning data to the rover. Thermal systems maintain a warm temperature during cruise to Mars to avoid contamination on the optics, and cool the detectors during operations on Mars. Results obtained with the integrated instrument demonstrate its capabilities for LIBS, for which a library of 332 standards was developed. Examples of Raman and VISIR spectroscopy are shown, demonstrating clear mineral identification with both techniques. Luminescence spectra demonstrate the utility of having both spectral and temporal dimensions. Finally, RMI and microphone tests on the rover demonstrate the capabilities of these subsystems as well