Adult-Onset Still's disease (AOSD) is a rare condition of unknown origin with various presentations and unpredictable outcome. The aim of this study was to analyse clinical and biological ...presentation, and outcome of patients admitted to an internal medicine service.
A retrospective cohort design with prospective follow-up was used. All the patients admitted to our internal medicine service for AOSD between January 1998 and March 2004 were included.
According to Yamaguchi's classification criteria, 17 patients were analysed with a mean age at onset of 37.3 years and a 2.4 sex-ratio (female/male). Mean follow-up length was 52.1 months. Eight patients developed a monocyclic systemic form, 8 a polycyclic systemic form and 1 a chronic articular form. Arthralgia (87%) and arthritis (53%) were less frequent than in other series. Sixteen patients were treated: 14 by corticosteroids, 6 by non-steroid anti-inflammatory drugs, 5 by methotrexate, 2 intravenous polyglobulin and one by anti-TNF drug. Patients with a corticodependant or corticoresistant form had more polyarthritis at the onset of the disease (3/6 vs 0/11, P=0.029).
In internal medicine activity, AOSD without oligo- or polyarthritis may be more frequent than expected according to the literature. Corticotherapy alone is often efficient in these AOSD form without synovitis, and methotrexate use is uncommon.
An innovative concept of activation of electrode materials for Li-ion batteries is proposed through the preparation of carbon-phosphorus (P/C) composites. Carbon-encapsulated phosphorus composites ...can be successfully prepared via a simple route by the vaporization–condensation of red phosphorus onto mesoporous carbon. Surface area measurements and Raman spectroscopy were used for the characterization of the P/C composites, which were then tested as anode materials in Li-ion batteries showing enhanced electrochemical properties. In contrast to what is observed for pure unsupported phosphorus, Li storage in P/C composite occurs through the reversible formation of Li
3P during the discharge process, as clearly evidenced by
in situ XRD, leading to capacities greater than 900
mAh
g
−1 after 20
cycles.
Abstract We present an implementation of a Bayesian mixture model using Hamiltonian Monte Carlo techniques to search for the spatial separation of Galactic dust populations. Utilizing intensity ...measurements from the Planck High Frequency Instrument, we apply this model to high-latitude Galactic dust emission. Our analysis reveals a strong preference for a spatially varying two-population dust model over a one-population dust model, when the latter must capture the total variance in the sky. Each dust population is well characterized by a single-component spectral energy distribution (SED) and accommodates small variations. These populations could signify two distinct components or may originate from a one-component model with different temperatures resulting in different SED scalings. While no spatial information is built into the likelihood, our investigation unveils large-scale spatially coherent structures with high significance, pointing to a physical origin for the observed spatial variation. These results are robust to our choice of likelihood and input data. Furthermore, this spatially varying two-population model is the most favored from Bayesian evidence calculations. Incorporating IRAS 100 μ m to constrain the Wein side of the blackbody function, we find the dust populations differ at the 2.5 σ level in the spectral index ( β d ) versus temperature ( T d ) plane. The presence of multiple dust populations has implications for component separation techniques frequently employed in the recovery of the cosmic microwave background.
Alterations in metabolic activities are cancer hallmarks that offer a wide range of new therapeutic opportunities. Here we decipher the interplay between mTORC1 activity and glucose metabolism in ...acute myeloid leukemia (AML). We show that mTORC1 signaling that is constantly overactivated in AML cells promotes glycolysis and leads to glucose addiction. The level of mTORC1 activity determines the sensitivity of AML cells to glycolysis inhibition as switch-off mTORC1 activity leads to glucose-independent cell survival that is sustained by an increase in mitochondrial oxidative phosphorylation. Metabolic analysis identified the pentose phosphate pathway (PPP) as an important pro-survival pathway for glucose metabolism in AML cells with high mTORC1 activity and provided a clear rational for targeting glucose-6-phosphate dehydrogenase (G6PD) in AML. Indeed, our analysis of the cancer genome atlas AML database pinpointed G6PD as a new biomarker in AML, as its overexpression correlated with an adverse prognosis in this cohort. Targeting the PPP using the G6PD inhibitor 6-aminonicotinamide induces in vitro and in vivo cytotoxicity against AML cells and synergistically sensitizes leukemic cells to chemotherapy. Our results demonstrate that high mTORC1 activity creates a specific vulnerability to G6PD inhibition that may work as a new AML therapy.
▶ Decision support system to monitor and predict the risk of diseases. ▶ Reducing the fungicide applications following the recommendations of the system. ▶ Using leaf wetness and temperature to ...predict disease outbreaks.
Florida produces about 16 million flats of strawberries every year, 15% of berries produced in the U.S. and virtually all the berries grown in the winter. Fungicides are applied on a weekly schedule to control Anthracnose and Botrytis fruit rot from December through March. Different predictive models for these diseases were evaluated and systems developed to time fungicide applications that reduced the number of sprays by about 50%. The models utilized leaf wetness and temperature during the wet period to predict disease outbreaks. The most effective models were embedded in a web-based tool developed for use by growers to schedule their fungicide applications. This internet-based forecasting system to predict these diseases, the Strawberry Advisory System (SAS), was implemented on the AgroClimate website using weather data from the Florida Agricultural Weather Network. Growers can select the location closest to their plantings and SAS will provide a prediction of disease incidence and recommendations for fungicide applications. Users can also be provided warnings of the need to spray via email or text messages. In preliminary trials, SAS has been successful in eliminating many unnecessary fungicide applications and has proven user friendly.
We investigated the immunoinflammatory profile of patients successfully resuscitated after cardiac arrest, representing a model of whole-body ischemia/reperfusion syndrome.
Plasma cytokine, ...endotoxin, and ex vivo cytokine production in whole-blood assays was assessed in 61, 35, and 11 patients, respectively. On admission, high levels of plasma interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor (TNF) receptor type II could discriminate between survivors and nonsurvivors. Among nonsurvivors, the initial need for a vasopressor agent was associated with higher levels of IL-1 receptor antagonist, IL-10, and IL-6 on day 1. Plasma endotoxin was detected in 46% of the analyzed patients within the 2 first days. Endotoxin-induced TNF and IL-6 productions were dramatically impaired in these patients compared with healthy control subjects, whereas an unaltered production was observed with heat-killed Staphylococcus aureus. In contrast, IL-1 receptor antagonist productions were enhanced in these patients compared with healthy control subjects. The productions of T-cell-derived IL-10 and interferon-gamma were also impaired in these patients. Finally, using in vitro plasma exchange between healthy control subjects and patients, we demonstrated that the endotoxin-dependent hyporeactivity was an intrinsic property of patients' leukocytes and that an immunosuppressive activity was also present in their plasma.
Altogether, the high levels of circulating cytokines, the presence of endotoxin in plasma, and the dysregulated production of cytokines found in these patients recall the immunological profile found in patients with sepsis.
Classical phase 1 dose-finding designs based on a single toxicity endpoint to assess the maximum tolerated dose were initially developed in the context of cytotoxic drugs. With the emergence of ...molecular targeted agents and immunotherapies, the concept of optimal biological dose (OBD) was subsequently introduced to account for efficacy in addition to toxicity. The objective was therefore to provide an overview of published phase 1 cancer clinical trials relying on the concept of OBD.
We performed a systematic review through a computerized search of the MEDLINE database to identify early phase cancer clinical trials that relied on OBD. Relevant publications were selected based on a two-step process by two independent readers. Relevant information (phase, type of therapeutic agents, objectives, endpoints and dose-finding design) were collected.
We retrieved 37 articles. OBD was clearly mentioned as a trial objective (primary or secondary) for 22 articles and was traditionally defined as the smallest dose maximizing an efficacy criterion such as biological target: biological response, immune cells count for immunotherapies, or biological cell count for targeted therapies. Most trials considered a binary toxicity endpoint defined in terms of the proportion of patients who experienced a dose-limiting toxicity. Only two articles relied on an adaptive dose escalation design.
In practice, OBD should be a primary objective for the assessment of the recommended phase 2 dose (RP2D) for a targeted therapy or immunotherapy phase I cancer trial. Dose escalation designs have to be adapted accordingly to account for both efficacy and toxicity.
Simplified models and details models are presented and compared. The Thomson effect must not be used when the Seebeck coefficient is constant. The improved simplified model presents good accuracy in ...TEC and TEG. Standard simplified model presents good accuracy in TEC/TEH. Analogy model gives the same results as the reference model (TEC and TEG).
Simplified models are usually used to describe the behavior of thermoelectric elements due to their low computational effort needed for solving the physical behavior in a wide number of situations (e.g., in both heating/cooling mode – TEH or TEC – and in power generation mode – TEG). The accuracy of these models depends on different assumptions like: (i) the Thomson effect is assumed to be negligible and (ii) the thermoelectric properties are assumed to be constant in the thermoelectric leg and are estimated from the mean temperature of its two sides.
This paper attempts to analyze simplified models’ accuracy, with regards to the performance (COP, efficiency), the voltage–current characteristics and the thermal/electrical power. The simplified models are compared to more accurate models, such as models based on an electrical analogy and on the finite element method (FEM). The benefits and drawbacks of each kind of model are discussed in order to help select the appropriate approach depending of the goal aimed. The improved simplified model using two different Seebeck coefficients with a constant Thomson coefficient greatly increases the accuracy of the results, particularly in TEG mode with large temperature differences between the two sides. The model based on the electrical analogy gives an intermediate approach between simplified models and FEM models. For one-dimensional modeling, the analogical model gives strictly the same results as those obtained with ANSYS (FEM-based software). In all the cases, we show that the key point is to use a null Thomson coefficient when a constant Seebeck coefficient is defined.
To describe presentation, hospital course, and predictors of bad outcome in multisystem inflammatory syndrome in children (MIS-C).
Retrospective data review of a case series of children meeting the ...published definition for MIS-C who were discharged or died between March 1, 2020, and June 15, 2020, from 33 participating European, Asian, and American hospitals. Data were collected through a Web-based survey and included clinical, laboratory, electrocardiographic, and echocardiographic findings and treatment management.
We included 183 patients with MIS-C: male sex, 109 (59.6%); mean age 7.0 ± 4.7 years; Black race, 56 (30.6%); obesity, 48 (26.2%). Overall, 114 of 183 (62.3%) had evidence of severe acute respiratory syndrome coronavirus 2 infection. All presented with fever, 117 of 183 (63.9%) with gastrointestinal symptoms, and 79 of 183 (43.2%) with shock, which was associated with Black race, higher inflammation, and imaging abnormalities. Twenty-seven patients (14.7%) fulfilled criteria for Kawasaki disease. These patients were younger and had no shock and fewer gastrointestinal, cardiorespiratory, and neurologic symptoms. The remaining 77 patients (49.3%) had mainly fever and inflammation. Inotropic support, mechanical ventilation, and extracorporeal membrane oxygenation were indicated in 72 (39.3%), 43 (23.5%), and 4 (2.2%) patients, respectively. A shorter duration of symptoms before admission was found to be associated with poor patient outcome and for extracorporeal membrane oxygenation and/or death, with 72.3% (95% confidence interval: 0.56-0.90;
= .006) increased risk per day reduction and 63.3% (95% confidence interval: 0.47-0.82;
< .0001) increased risk per day reduction respectively.
In this case series, children with MIS-C presented with a wide clinical spectrum, including Kawasaki disease-like, life-threatening shock and milder forms with mainly fever and inflammation. A shorter duration of symptoms before admission was associated with a worse outcome.
This study aimed at the real-time estimation of the lower-limb joint and torso kinematics during a squat exercise, performed in the sagittal plane, using a single inertial measurement unit placed on ...the lower back. The human body was modeled with a 3-DOF planar chain. The planar IMU orientation and vertical displacement were estimated using one angular velocity and two acceleration components and a weighted Fourier linear combiner. The ankle, knee, and hip joint angles were thereafter obtained through a novel inverse kinematic module based on the use of a Jacobian pseudoinverse matrix and null-space decoupling. The aforementioned algorithms were validated on a humanoid robot for which the mechanical model used and the measured joint angles virtually exhibited no inaccuracies. Joint angles were estimated with a maximal error of 1.5°. The performance of the proposed analytical and experimental methodology was also assessed by conducting an experiment on human volunteers and by comparing the relevant results with those obtained through the more conventional photogrammetric approach. The joint angles provided by the two methods displayed differences equal to 3 ± 1°. These results, associated with the real-time capability of the method, open the door to future field applications in both rehabilitation and sport.
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