Constrained path planning for manned–unmanned rotorcraft teaming in emergency medical service missions

This paper investigates the path-planning problem applied to an innovative Unmanned Air Vehicle teaming with a helicopter to increase safety during Helicopter Emergency Medical Services operations. The unmanned vehicle, a drone that optionally can be launched from the helicopter, has the mission to explore the area of operation to determine the meteorological and environmental conditions and to detect physical obstacles. It is initially found that the combination of probabilistically optimal Rapidly-exploring Random Tree (RRT*) as the global planner and of Bidirectional Rapidly-exploring Random Tree (BiRRT) as the local planner provides a nearly optimal global path and a rapid replanning in case new obstacles are detected. Adopting a Savitzky–Golay filter in an optional post-processing phase enables trajectory smoothing, thus improving its practicability. The feasibility of the identified trajectory for a rigid-body helicopter model is assessed by computing a first estimate of attitude, forces, control inputs, and rotor power from the trajectory points and curvature. This assessment shows that the RRT* used as a local planner provides replanned trajectories more feasible than BiRRT with comparable computational times

A Practical Guide to Estimating Coil Inductance for Magnetic Resonance Applications

Radiofrequency (RF) coils are employed to transmit and/or receive signals in Magnetic Resonance (MR) systems. The design of home-made, organ-specific RF coils with optimized homogeneity and/or Signal-to-Noise Ratio (SNR) can be a plus in many research projects. The first step requires accurate inductance calculation, this depending on the conductor's geometry, to later define the tuning capacitor necessary to obtain the desired resonance frequency. To fulfil such a need it is very useful to perform a priori inductance estimation rather than relying on the time-consuming trial-and-error approach. This paper describes and compares two different procedures for coil inductance estimation to allow for a fast coil-prototyping process. The first method, based on calculations in the quasi-static approximation, permits an investigation on how the cross-sectional geometry of the RF coil conductors affects the total inductance and can be easily computed for a wide variety of coil geometries. The second approach uses a numerical full-wave method based on the Finite-Difference Time-Domain (FDTD) algorithm, and permits the simulation of RF coils with any complex geometry, including the case of multi-element phased array. Comparison with workbench measurements validates both the analytical and numerical results for RF coils operating within a wide field range (0.18–7 T)

Specific ADAM10 inhibitors localize in exosome-like vesicles released by Hodgkin lymphoma and stromal cells and prevent sheddase activity carried to bystander cells

Shedding of ADAM10 substrates, like TNFa, MICA or CD30, is reported to affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. Soluble forms of these molecules and ADAM10 can be carried and spread in the microenvironment by exosomes released by tumor cells. We reported new ADAM10 inhibitors able to prevent MICA shedding in Hodgkin lymphoma (HL), leading to recognition of HL cells by cytotoxic lymphocytes. In this paper, we show that the mature bioactive form of ADAM10 is released in exosome-like vesicles (ExoV) by HL cells and lymph node mesenchymal stromal cells (MSC). We demonstrate that ADAM10 inhibitors are released in ExoV by MSC or HL cells, endocytosed by bystander cells and localized in the endolysosomal compartment in HL MSC. ExoV released by HL cells can enhance MICA shedding by MSC, while ExoV from MSC induce TNFa or CD30 shedding by HL cells. Of note, ADAM10 sheddase activity carried by ExoV is prevented with the ADAM10 inhibitors LT4 and CAM29, pretreating either the ExoVproducing or the ExoV-receiving cells. In particular, both inhibitors reduce CD30 shedding maintaining the anti-tumor effects of the ADC Brentuximab-Vedotin or the anti-CD30 Iratumumab on HL cells. Thus, spreading of ADAM10 activity due to ExoV can result in the release of cytokines, like TNFa,a lymphoma growth factor, or soluble molecules, like sMICA or sCD30, that potentially interfere with host immune surveillance or immunotherapy. ADAM10 blockers can interfere with this process, allowing the development of anti-lymphoma immune response and/or efficient ADC-based or human antibody-based immunotherapy

Intracoronary physiology-guided percutaneous coronary intervention in patients with diabetes

Objective: The risk of vessel-oriented cardiac adverse events (VOCE) in patients with diabetes mellitus (DM) undergoing intracoronary physiology-guided coronary revascularization is poorly defined. The purpose of this work is to evaluate the risk of VOCE in patients with and without DM in whom percutaneous coronary intervention (PCI) was performed or deferred based on pressure-wire functional assessment. Methods: This is a retrospective analysis of a multicenter registry of patients evaluated with fractional flow reserve (FFR) and/or non-hyperaemic pressure ratio (NHPR). Primary endpoint was a composite of VOCE including cardiac death, vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR). Results: A large cohort of 2828 patients with 3353 coronary lesions was analysed to assess the risk of VOCE at long-term follow-up (23 [14-36] months). Non-insulin-dependent-DM (NIDDM) was not associated with the primary endpoint in the overall cohort (adjusted Hazard Ratio [aHR] 1.18, 95% CI 0.87-1.59, P = 0.276) or in patients with coronary lesions treated with PCI (aHR = 1.30, 95% CI 0.78-2.16, P = 0.314). Conversely, insulin-dependent diabetes mellitus (IDDM) demonstrated an increased risk of VOCE in the overall cohort (aHR 1.76, 95% CI 1.07-2.91, P = 0.027), but not in coronary lesions undergoing PCI (aHR 1.26, 95% CI 0.50-3.16, P = 0.621). Importantly, in coronary lesions deferred after functional assessment IDDM (aHR 2.77, 95% CI 1.11-6.93, P = 0.029) but not NIDDM (aHR = 0.94, 95% CI 0.61-1.44, P = 0.776) was significantly associated with the risk of VOCE. IDDM caused a significant effect modification of FFR-based risk stratification (P for interaction < 0.001). Conclusion: Overall, DM was not associated with an increased risk of VOCE in patients undergoing physiology-guided coronary revascularization. However, IDDM represents a phenotype at high risk of VOCE

Deep Broadband Observations of the Distant Gamma-ray Blazar PKS 1424+240

We present deep VERITAS observations of the blazar PKS 1424+240, along with contemporaneous Fermi Large Area Telescope, Swift X-ray Telescope and Swift UV Optical Telescope data between 2009 February 19 and 2013 June 8. This blazar resides at a redshift of $z\ge0.6035$, displaying a significantly attenuated gamma-ray flux above 100 GeV due to photon absorption via pair-production with the extragalactic background light. We present more than 100 hours of VERITAS observations from three years, a multiwavelength light curve and the contemporaneous spectral energy distributions. The source shows a higher flux of (2.1$\pm0.3$)$\times10^{-7}$ ph m$^{-2}$s$^{-1}$ above 120 GeV in 2009 and 2011 as compared to the flux measured in 2013, corresponding to (1.02$\pm0.08$)$\times10^{-7}$ ph m$^{-2}$s$^{-1}$ above 120 GeV. The measured differential very high energy (VHE; $E\ge100$ GeV) spectral indices are $\Gamma=$3.8$\pm$0.3, 4.3$\pm$0.6 and 4.5$\pm$0.2 in 2009, 2011 and 2013, respectively. No significant spectral change across the observation epochs is detected. We find no evidence for variability at gamma-ray opacities of greater than $\tau=2$, where it is postulated that any variability would be small and occur on longer than year timescales if hadronic cosmic-ray interactions with extragalactic photon fields provide a secondary VHE photon flux. The data cannot rule out such variability due to low statistics.Comment: ApJL accepted March 17, 201

Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia

Leukemia stem cells (LSCs) in individuals with chronic myelogenous leukemia (CML) (hereafter referred to as CML LSCs) are responsible for initiating and maintaining clonal hematopoiesis. These cells persist in the bone marrow (BM) despite effective inhibition of BCR–ABL kinase activity by tyrosine kinase inhibitors (TKIs). Here we show that although the microRNA (miRNA) miR-126 supported the quiescence, self-renewal and engraftment capacity of CML LSCs, miR-126 levels were lower in CML LSCs than in long-term hematopoietic stem cells (LT-HSCs) from healthy individuals. Downregulation of miR-126 levels in CML LSCs was due to phosphorylation of Sprouty-related EVH1-domain-containing 1 (SPRED1) by BCR–ABL, which led to inhibition of the RAN–exportin-5–RCC1 complex that mediates miRNA maturation. Endothelial cells (ECs) in the BM supply miR-126 to CML LSCs to support quiescence and leukemia growth, as shown using mouse models of CML in which Mir126a (encoding miR-126) was conditionally knocked out in ECs and/or LSCs. Inhibition of BCR–ABL by TKI treatment caused an undesired increase in endogenous miR-126 levels, which enhanced LSC quiescence and persistence. Mir126a knockout in LSCs and/or ECs, or treatment with a miR-126 inhibitor that targets miR-126 expression in both LSCs and ECs, enhanced the in vivo anti-leukemic effects of TKI treatment and strongly diminished LSC leukemia-initiating capacity, providing a new strategy for the elimination of LSCs in individuals with CML

ECLAPTE: Effective Closure of LAParoTomy in Emergency-2023 World Society of Emergency Surgery guidelines for the closure of laparotomy in emergency settings

Laparotomy incisions provide easy and rapid access to the peritoneal cavity in case of emergency surgery. Incisional hernia (IH) is a late manifestation of the failure of abdominal wall closure and represents frequent complication of any abdominal incision: IHs can cause pain and discomfort to the patients but also clinical serious sequelae like bowel obstruction, incarceration, strangulation, and necessity of reoperation. Previous guidelines and indications in the literature consider elective settings and evidence about laparotomy closure in emergency settings is lacking. This paper aims to present the World Society of Emergency Surgery (WSES) project called ECLAPTE (Effective Closure of LAParoTomy in Emergency): the final manuscript includes guidelines on the closure of emergency laparotomy

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Parque eólico como paisaje cultural "Eau de vent"

Le Vallée de l'Agly. Tema 4: Eólico