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Ultrafast laser pulse filamentation in the air can be used for remote sensing by exciting a characteristic optical emission, which is usually referred to as filamentation-induced breakdown spectroscopy. In environments that impede light propagation, such as fog, haze, or clouds, scattering makes it challenging to propagate laser beams and retrieve generated optical signatures. We demonstrate the effectiveness of laser filamentation for simultaneously clearing the path for intense femtosecond pulse propagation in a highly scattering medium, generation of luminous plasma on a solid target, and counter-propagation of a characteristic spectroscopic signal over a cleared channel along the filament path. In a dense cloud, the counter-propagating signal predominantly transits the cleared on-axis path but is highly affected by the negative thermal lensing of a Gaussian beam. These insights enhance our understanding of laser filamentation in atmospheric sensing and could substantially improve remote detection capabilities in poor visibility conditions.
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Molten salts have a significant potential for use as next-generation nuclear reactor coolants and in pyroprocessing for the recycling of used nuclear fuel. However, the molten salt composition needs to be known at all times, and high temperatures and intense ionizing radiation pose challenges for the monitoring instrumentation. Although the technique of laser-induced breakdown spectroscopy (LIBS) has been studied for in situ measurements of molten salts, trials to improve its monitoring accuracy using chemometrics are lacking. In this study, a data fusion technique using the LIBS optical and laser-induced acoustic (LIA) signals was investigated to enhance the measurement accuracy for molten salt monitoring. Prediction models were constructed using the partial least-squares method, and the variable importance in projection scores was analyzed to evaluate the effect of incorporating the LIA signal into the analysis. This study investigates rare earth elements Eu, Er, and Pr found not only in nuclear but also in other settings such as laser and magnetic materials. The analysis of LIBS data without data fusion resulted in a root-mean-square error of prediction (RMSEP) of 0.0774-0.0913 wt %, whereas the prediction model using data fusion led to approximately 18-40% enhanced RMSEP (0.0461-0.0679 wt %). The results suggest that fusing the LIBS data with the simultaneously recorded LIA data can improve the monitoring accuracy of rare earth element composition in molten salts.
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This study aimed to comprehensively understand the performance and degradation of both p- and n-channel vertical double diffused MOS (VDMOS) transistors under bias temperature stress. Conducted experimental investigations involved various stress conditions and annealing processes to analyze the impacts of BT stress on the formation of oxide trapped charge and interface traps, leading to threshold voltage shifts. Findings revealed meaningful threshold voltage shifts in both PMOS and NMOS devices due to stresses, and the subsequent annealing process was analyzed in detail. The study also examined the influence of stress history on self-heating behavior under real operating conditions. Additionally, the study elucidated the complex correlation between stress-induced degradation and device reliability. The insights contribute to optimizing the performance and permanence of VDMOS transistors in practical applications, advancing semiconductor technology. This study underscored the importance of considering stress-induced effects on device reliability and performance in the design and application of VDMOS transistors.
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The optical filament-based radioxenon sensing can potentially overcome the constraints of conventional detection techniques that are relevant for nuclear security applications. This study investigates the spectral signatures of pure xenon (Xe) when excited by ultrafast laser filaments at near-atmosphericpressure and in short and loose-focusing conditions. The two focusing conditions lead to laser intensity differences of several orders of magnitude and different plasma transient behavior. The gaseous sample was excited at atmospheric pressure using â¼7 mJ pulses with a 35 fs pulse duration at 800 nm wavelength. The optical signatures were studied by time-resolved spectrometry and imaging in orthogonal light collection configurations in the â¼400 nm (VIS) and â¼800 nm (NIR) spectral regions. The most prominent spectral lines of atomic Xe are observable in both focusing conditions. An on-axis light collection from an atmospheric air-Xe plasma mixture demonstrates the potential of femtosecond filamentation for the remote sensing of noble gases.
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We present an ultrafast long-wave infrared (LWIR) source driven by a mid-infrared fluoride fiber laser. It is based on a mode-locked Er:ZBLAN fiber oscillator and a nonlinear amplifier operating at 48 MHz. The amplified soliton pulses at â¼2.9 µm are shifted to â¼4 µm via the soliton self-frequency shifting process in an InF3 fiber. LWIR pulses with an average power of 1.25-mW centered at 11 µm with a spectral bandwidth of â¼1.3 µm are produced through difference-frequency generation (DFG) of the amplified soliton and its frequency-shifted replica in a ZnGeP2 crystal. Soliton-effect fluoride fiber sources operating in the mid-infrared for driving DFG conversion to LWIR enable higher pulse energies than with near-infrared sources, while maintaining relative simplicity and compactness, relevant for spectroscopy and other applications in LWIR.
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Alcoholic liver disease (ALD) is a consequence of excessive alcohol use. According to many studies, alcohol represents a significant socioeconomic and health risk factor in today's population. According to data from the World Health Organization, there are about 75 million people who have alcohol disorders, and it is well known that its use leads to serious health problems. ALD is a multimodality spectrum that includes alcoholic fatty liver disease (AFL) and alcoholic steatohepatitis (ASH), consequently leading to liver fibrosis and cirrhosis. In addition, the rapid progression of alcoholic liver disease can lead to alcoholic hepatitis (AH). Alcohol metabolism produces toxic metabolites that lead to tissue and organ damage through an inflammatory cascade that includes numerous cytokines, chemokines, and reactive oxygen species (ROS). In the process of inflammation, mediators are cells of the immune system, but also resident cells of the liver, such as hepatocytes, hepatic stellate cells, and Kupffer cells. These cells are activated by exogenous and endogenous antigens, which are called pathogen and damage-associated molecular patterns (PAMPs, DAMPs). Both are recognized by Toll-like receptors (TLRs), which activation triggers the inflammatory pathways. It has been proven that intestinal dysbiosis and disturbed integrity of the intestinal barrier perform a role in the promotion of inflammatory liver damage. These phenomena are also found in chronic excessive use of alcohol. The intestinal microbiota has an important role in maintaining the homeostasis of the organism, and its role in the treatment of ALD has been widely investigated. Prebiotics, probiotics, postbiotics, and symbiotics represent therapeutic interventions that can have a significant effect on the prevention and treatment of ALD.
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Fígado Gorduroso Alcoólico , Hepatopatias Alcoólicas , Microbiota , Humanos , Hepatopatias Alcoólicas/metabolismo , Etanol/metabolismo , Fígado/metabolismo , Inflamação/metabolismo , Fígado Gorduroso Alcoólico/metabolismoRESUMO
Increased absorption of optical materials arising from exposure to ionizing radiation must be accounted for to accurately analyze laser-induced breakdown spectroscopy (LIBS) data retrieved from high-radiation environments. We evaluate this effect on two examples that mimic the diagnostics placed within novel nuclear reactor designs. The analysis is performed on LIBS data measured with 1% Xe gas in an ambient He environment and 1% Eu in a molten LiCl-KCl matrix, along with the measured optical absorption from the gamma- and neutron-irradiated low-OH fused silica and sapphire glasses. Significant changes in the number of laser shots required to reach a 3σ detection level are observed for the Eu data, increasing by two orders of magnitude after exposure to a 1.7 × 1017 n/cm2 neutron fluence. For all cases examined, the spectral dependence of absorption results in the introduction of systematic errors. Moreover, if lines from different spectral regions are used to create Boltzmann plots, this attenuation leads to statistically significant changes in the temperatures calculated from the Xe II lines and Eu II lines, lowering them from 8000 ± 610 K to 6900 ± 810 K and from 15,800 ± 400 K to 7200 ± 800 K, respectively, for exposure to the 1.7 × 1017 n/cm2 fluence. The temperature range required for a 95% confidence interval for the calculated temperature is also broadened. In the case of measuring the Xe spectrum, these effects may be mitigated using only the longer-wavelength spectral region, where radiation attenuation is relatively small, or through analysis using the iterative Saha-Boltzmann method.
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Óxido de Alumínio , Análise de Dados , Masculino , Humanos , Vidro , Radiação Ionizante , Análise EspectralRESUMO
The proportion of elderly people in the world population is constantly increasing. With age, the risk of numerous chronic diseases and their complications also rises. Research on the subject of cellular senescence date back to the middle of the last century, and today we know that senescent cells have different morphology, metabolism, phenotypes and many other characteristics. Their main feature is the development of senescence-associated secretory phenotype (SASP), whose pro-inflammatory components affect tissues and organs, and increases the possibility of age-related diseases. The liver is the main metabolic organ of our body, and the results of previous research indicate that its regenerative capacity is greater and that it ages more slowly compared to other organs. With age, liver cells change under the influence of various stressors and the risk of developing chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH) and hepatocellular carcinoma (HCC) increases. It has been proven that these diseases progress faster in the elderly population and in some cases lead to end-stage liver disease that requires transplantation. The treatment of elderly people with chronic liver diseases is a challenge and requires an individual approach as well as new research that will reveal other safe and effective therapeutic modalities.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Idoso , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , EnvelhecimentoRESUMO
Plants and other photosynthetic organisms have been suggested as potential pervasive biosensors for nuclear nonproliferation monitoring. We demonstrate that ultrafast laser filament-induced fluorescence of chlorophyll in the green alga Chlamydomonas reinhardtii is a promising method for remote, in-field detection of stress from exposure to nuclear materials. This method holds an advantage over broad-area surveillance, such as solar-induced fluorescence monitoring, when targeting excitation of a specific plant would improve the detectability, for example when local biota density is low. After exposing C. reinhardtii to uranium, we find that the concentration of chlorophyll a, chlorophyll fluorescence lifetime, and carotenoid content increase. The increased fluorescence lifetime signifies a decrease in non-photochemical quenching. The simultaneous increase in carotenoid content implies oxidative stress, further confirmed by the production of radical oxygen species evidence in the steady-state absorption spectrum. This is potentially a unique signature of uranium, as previous work finds that heavy metal stress generally increases non-photochemical quenching. We identify the temporal profile of the chlorophyll fluorescence to be a distinguishing feature between uranium-exposed and unexposed algae. Discrimination of uranium-exposed samples is possible at a distance of [Formula: see text]35 m with a single laser shot and a modest collection system, as determined through a combination of experiment and simulation of distance-scaled uncertainty in discriminating the temporal profiles. Illustrating the potential for remote detection, detection over 125 m would require 100 laser shots, commensurate with the detection time on the order of 1 s.
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Chlamydomonas reinhardtii , Urânio , Carotenoides , Clorofila/química , Clorofila A , Fluorescência , Oxigênio , FotossínteseRESUMO
Background: The aim of this study was to identify risk factors contributing to the malignancy of colorectal polyps, as well as risk factors for recurrence after the successful endoscopic mucosal resection of large colorectal polyps in a referral center. Materials and Methods: This retrospective cohort study was performed in patients diagnosed with large (≥20 mm diameter) colorectal polyps and treated in the period from January 2014 to December 2019 at the University Hospital Medical Center Bezanijska Kosa, Belgrade, Serbia. Based on the endoscopic evaluation and classification of polyps, the following procedures were performed: en bloc resection, piecemeal resection or surgical treatment. Results: A total of 472 patients with large colorectal polyps were included in the study. The majority of the study population were male (62.9%), with a mean age of 65.7 ± 10.8 years. The majority of patients had one polyp (73.7%) less than 40 mm in size (74.6%) sessile morphology (46.4%), type IIA polyps (88.2%) or polyps localized in the descending colon (52.5%). The accessibility of the polyp was complicated in 17.4% of patients. En bloc resection was successfully performed in 61.0% of the patients, while the rate of piecemeal resection was 26.1%. Due to incomplete endoscopic resection, surgery was performed in 5.1% of the patients, while 7.8% of the patients were referred to surgery directly. Hematochezia (p = 0.001), type IIB polyps (p < 0.001) and complicated polyp accessibility (p = 0.002) were significant independent predictors of carcinoma presence in a multivariate logistic regression analysis. Out of the 472 patients enrolled in the study, 364 were followed after endoscopic resection for colorectal polyp recurrence, which was observed in 30 patients (8.2%) during follow-up. Piecemeal resection (p = 0.048) and incomplete resection success (p = 0.013) were significant independent predictors of polyp recurrence in the multivariate logistic regression analysis. Conclusions: Whenever an endoscopist encounters a complex colorectal lesion (i.e., a polyp with complicated accessibility), polyp size > 40 mm, the Laterally Spreading Tumor nongranular (LST-NG) morphological type, type IIB polyps or the presence of hematochezia, malignancy risk should be considered before making the decision to either resect, refer to an advanced endoscopist or perform surgery.
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Pólipos do Colo , Neoplasias Colorretais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Pólipos do Colo/cirurgia , Pólipos do Colo/patologia , Colonoscopia/métodos , Estudos Retrospectivos , Fatores de Risco , Hemorragia Gastrointestinal , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologiaRESUMO
Point-of-Care ultrasound (POCUS) is based on target ultrasound that is performed wherever a patient is being treated, and by a non-radiologist directly involved in the patient's care. It is used either for quick diagnosis or procedural guidance. Abdominal pain is one of the most common complaints in emergency departments, and POCUS can help in the differentiation of patients who need additional diagnostic tests or hospital treatment, which eventually reduces the overall costs of health care. POCUS has high sensitivity and specificity in abdominal pathology, it can be helpful in the evaluation of biliary, intestinal, and urinary tract, and it is especially used in trauma. Additionally, the gold standard for abdominal aortic aneurysm detection, follow up and screening is precisely this diagnostic procedure. Unfortunately, the quality of ultrasound examination can be affected by the experience of the physician performing it and the patient's body weight. There is no doubt that POCUS is being increasingly recognized, but all motivated physicians should be provided with dedicated tutors and enough time for learning. This would certainly help to implement this diagnostic method as a routine in emergency and critical care departments, and significantly shorten the time until definitive diagnosis.
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BACKGROUND: This study aimed to calculate the frequency of elevated liver enzymes in hospitalized patients with coronavirus disease 2019 (COVID-19) infection and to test if liver enzyme biochemistry levels on admission could predict the computed tomography (CT) scan severity score of bilateral interstitial pneumonia. METHODS: This single-center study comprised of 323 patients including their demographic data, laboratory analyses, and radiological findings. All the information was taken from electronic health records, followed by statistical analysis. RESULTS: Out of 323 patients, 115 of them (35.60%) had aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) over 40 U/L on admission. AST was the best predictor of CT scan severity score of bilateral interstitial pneumonia (R2 = 0.313, Adjusted R2 = 0.299). CT scan severity score in the peak of the infection could be predicted with the value of AST, neutrophils, platelets, and monocytes count (R2 = 0.535, Adjusted R2 = 0.495). CONCLUSION: AST, neutrophils, platelets, and monocytes count on admission can account for almost half (49.5%) of the variability in CT scan severity score at peak of the disease, predicting the extensiveness of interstitial pneumonia related to COVID-19 infection. Liver enzymes should be closely monitored in order to stratify COVID-19 patients with a higher risk of developing severe forms of the disease and to plan the beforehand step-up treatment.
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COVID-19 , Pneumonia , Alanina Transaminase , Aspartato Aminotransferases , Humanos , Estudos Retrospectivos , SARS-CoV-2RESUMO
Objective: To evaluate the nature and rate of sports injuries in medical students, as well as the risk factors at these events. Methods: All student-athletes (218) from a Medical School, integrated in at least one of the six team sport modalities (soccer, rugby, indoor soccer, handball, basketball, and volleyball) in 2017, were included. Injuries affecting their performance, regardless of time loss, were included. Athlete-exposure (A-E) was defined as one student-athlete participating in one practice or game. Results: Injury rates were significantly higher in junior medical students (1st - 3rd year) (7.58 per 1000 A-E, 95%CI = 6.11-9.06) than in senior medical students (4th - 6th year) (4.49 per 1000 A-E, 95%CI = 3.26-5.73) (p < 0.001). Multi-sports athletes had higher injury rates (10.69 per 1000 A-E, 95%CI = 8.22-13.17) than single-sport athletes (4.49 per 1000 A-E, 95%CI = 3.51-5.47) (p = 0.002). More than 60% of reported injuries occurred in the lower limbs and the mechanism that accounted for most injuries in games was player contact (51%); whereas in practice, it was non-contact (53%). Conclusion: Junior medical students present a higher injury rate than seniors. Medical students practicing more than one modality had a higher injury rate than those involved in just one sport modality. Level of Evidence IV, Cross-Sectional Study.
Objetivo: Avaliar a incidência e as características das lesões esportivas em alunos de medicina, assim como os fatores de risco envolvidos. Métodos: Todos os alunos (218) da Faculdade de Medicina da Universidade de São Paulo que integravam seis modalidades esportivas (futebol, rugby, futsal, handebol, basquete e vôlei) em 2017 foram incluídos. Foram incluídas as lesões que afetaram a performance, independente do tempo de afastamento. Uma exposição-atleta (E-A) foi definida como a participação de um aluno em um jogo ou treino. Resultados: A taxa de lesão foi maior em alunos do 1º ao 3º ano (7,58 por 1000 E-As 95% IC = 6,11-9,06) do que em alunos do 4º ao 6º ano (4,49 por 1000 E-As 95% IC = 3,26-5,73) (p < 0.001).Alunos praticantes de mais de uma modalidade apresentaram maior taxa de lesão (10,69 por 1000 E-As, 95% IC 8,22-13,17) do que alunos praticantes de apenas uma modalidade (4.49 por 1000 E-As, 95% IC 3,51-5,47) (p = 0.002). Mais de 60% daslesões ocorreram nos membros inferiores e o principal mecanismo em jogos foi contato com outro jogador (51%), e em treinos foi lesão sem contato (53%). Conclusão: Alunos do 1 Ë ao 3 Ë ano apresentaram maior taxa de lesão do que alunos do 4º ao 6º ano. Alunos praticantes de mais de uma modalidade apresentaram maior taxa de lesão do que alunos praticantes de apenas uma modalidade. Nível de Evidência IV, Estudo Transversal.
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The emerging issues nowadays are non-alcoholic fatty liver disease (NAFLD) and its advanced stage non-alcoholic steatohepatitis (NASH), which further can be a predisposing factor for chronic liver complications, such as cirrhosis and/or development of hepatocellular carcinoma (HCC). Liver lipotoxicity can influence the accumulation of reactive oxygen species (ROS), so oxidative stress is also crucial for the progression of NASH. Moreover, NASH is in strong connection with metabolic disorders, and supporting evidence shows that insulin resistance (IR) is in a close relation to NAFLD, as it is involved in the progression to NASH and further progression to hepatic fibrosis. The major issue is that, at the moment, NASH treatment is based on lifestyle changes only due to the fact that no approved therapeutic options are available. The development of new therapeutic strategies should be conducted towards the potential NAFLD and NASH treatment by the modulation of IR but also by dietary antioxidants. As it seems, NASH is going to be the leading indication for liver transplantation as a consequence of increased disease prevalence and the lack of approved treatment; thus, an effective solution is needed as soon as possible.
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Carcinoma Hepatocelular , Resistência à Insulina , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/metabolismo , Progressão da Doença , Humanos , Fígado/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
In order to model the fate and transport of particles following a nuclear explosion, there must first be an understanding of individual physical and chemical processes that affect particle formation. One interaction pertinent to fireball chemistry and resultant debris formation is that between uranium and oxygen. In this study, we use laser ablation of uranium metal in different concentrations of oxygen gas, either 16O2 or 18O2, to determine the influence of oxygen on rapidly cooling uranium. Analysis of recovered particulates using infrared absorption and Raman spectroscopies indicate that the micrometer-sized particulates are predominantly amorphous UOx (am-UOx, where 3 ≤ x ≤ 4) and UO2 after ablation in 1 atm of pure O2 and a 1% O2/Ar mixture, respectively. Energy dispersive X-ray spectroscopy (EDS) of particulates formed in pure O2 suggest an O/U ratio of ~ 3.7, consistent with the vibrational spectroscopy analysis. Both am-UOx and UO2 particulates convert to α-U3O8 when heated. Lastly, experiments performed in 18O2 environments show the formation of 18O-substituted uranium oxides; vibrational frequencies for am-U18Ox are reported for the first time. When compared to literature, this work shows that cooling timescales can affect the structural composition of uranium oxides (i.e., crystalline vs. amorphous). This indicator can be used in current models of nuclear explosions to improve our predicative capabilities of chemical speciation.
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ABSTRACT Objective: To evaluate the nature and rate of sports injuries in medical students, as well as the risk factors at these events. Methods: All student-athletes (218) from a Medical School, integrated in at least one of the six team sport modalities (soccer, rugby, indoor soccer, handball, basketball, and volleyball) in 2017, were included. Injuries affecting their performance, regardless of time loss, were included. Athlete-exposure (A-E) was defined as one student-athlete participating in one practice or game. Results: Injury rates were significantly higher in junior medical students (1st - 3rd year) (7.58 per 1000 A-E, 95%CI = 6.11-9.06) than in senior medical students (4th - 6th year) (4.49 per 1000 A-E, 95%CI = 3.26-5.73) (p < 0.001). Multi-sports athletes had higher injury rates (10.69 per 1000 A-E, 95%CI = 8.22-13.17) than single-sport athletes (4.49 per 1000 A-E, 95%CI = 3.51-5.47) (p = 0.002). More than 60% of reported injuries occurred in the lower limbs and the mechanism that accounted for most injuries in games was player contact (51%); whereas in practice, it was non-contact (53%). Conclusion: Junior medical students present a higher injury rate than seniors. Medical students practicing more than one modality had a higher injury rate than those involved in just one sport modality. Level of Evidence IV, Cross-Sectional Study.
RESUMO Objetivo: Avaliar a incidência e as características das lesões esportivas em alunos de medicina, assim como os fatores de risco envolvidos. Métodos: Todos os alunos (218) da Faculdade de Medicina da Universidade de São Paulo que integravam seis modalidades esportivas (futebol, rugby, futsal, handebol, basquete e vôlei) em 2017 foram incluídos. Foram incluídas as lesões que afetaram a performance, independente do tempo de afastamento. Uma exposição-atleta (E-A) foi definida como a participação de um aluno em um jogo ou treino. Resultados: A taxa de lesão foi maior em alunos do 1º ao 3º ano (7,58 por 1000 E-As 95% IC = 6,11-9,06) do que em alunos do 4º ao 6º ano (4,49 por 1000 E-As 95% IC = 3,26-5,73) (p < 0.001). Alunos praticantes de mais de uma modalidade apresentaram maior taxa de lesão (10,69 por 1000 E-As, 95% IC 8,22-13,17) do que alunos praticantes de apenas uma modalidade (4.49 por 1000 E-As, 95% IC 3,51-5,47) (p = 0.002). Mais de 60% das lesões ocorreram nos membros inferiores e o principal mecanismo em jogos foi contato com outro jogador (51%), e em treinos foi lesão sem contato (53%). Conclusão: Alunos do 1 ˚ ao 3 ˚ ano apresentaram maior taxa de lesão do que alunos do 4º ao 6º ano. Alunos praticantes de mais de uma modalidade apresentaram maior taxa de lesão do que alunos praticantes de apenas uma modalidade. Nível de Evidência IV, Estudo Transversal.
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The use of optical instrumentation in advanced nuclear fission systems, such as molten salt reactors, liquid metal-cooled reactors, and high-temperature gas-cooled reactors, has the potential to enhance reactor safety and economic performance through in situ and online measurement of reactor conditions. Selection of suitable optical components, such as optical windows and fibers, is essential for operation of optical instrumentation in intense radioactive and thermal environments inherent to nuclear reactor systems. We present the development and performance of a self-contained and mobile post-irradiation examination system for rapid characterization of the optical properties of materials. The instrument combines linear absorption and nanosecond Z-scan modules in a compact, relocatable design. The system mobility allows for the evaluation of optical samples at the site of irradiation, minimizing the delay between extraction from the irradiation site and optical characterization. This provides nearly real-time information on the material performance under simultaneous irradiation and thermal annealing, simulating the relevant conditions for the use of those components in nuclear power systems.
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BACKGROUND: Ozanimod, a selective sphingosine-1-phosphate receptor modulator, is under investigation for the treatment of inflammatory bowel disease. METHODS: We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. In the 10-week induction period, patients in cohort 1 were assigned to receive oral ozanimod hydrochloride at a dose of 1 mg (equivalent to 0.92 mg of ozanimod) or placebo once daily in a double-blind manner, and patients in cohort 2 received open-label ozanimod at the same daily dose. At 10 weeks, patients with a clinical response to ozanimod in either cohort underwent randomization again to receive double-blind ozanimod or placebo for the maintenance period (through week 52). The primary end point for both periods was the percentage of patients with clinical remission, as assessed with the three-component Mayo score. Key secondary clinical, endoscopic, and histologic end points were evaluated with the use of ranked, hierarchical testing. Safety was also assessed. RESULTS: In the induction period, 645 patients were included in cohort 1 and 367 in cohort 2; a total of 457 patients were included in the maintenance period. The incidence of clinical remission was significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6.0%, P<0.001) and maintenance (37.0% vs. 18.5% [among patients with a response at week 10], P<0.001). The incidence of clinical response was also significantly higher with ozanimod than with placebo during induction (47.8% vs. 25.9%, P<0.001) and maintenance (60.0% vs. 41.0%, P<0.001). All other key secondary end points were significantly improved with ozanimod as compared with placebo in both periods. The incidence of infection (of any severity) with ozanimod was similar to that with placebo during induction and higher than that with placebo during maintenance. Serious infection occurred in less than 2% of the patients in each group during the 52-week trial. Elevated liver aminotransferase levels were more common with ozanimod. CONCLUSIONS: Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. (Funded by Bristol Myers Squibb; True North ClinicalTrials.gov number, NCT02435992.).
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Colite Ulcerativa/tratamento farmacológico , Indanos/uso terapêutico , Oxidiazóis/uso terapêutico , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Adulto , Bradicardia/induzido quimicamente , Método Duplo-Cego , Feminino , Humanos , Hipertensão/induzido quimicamente , Indanos/efeitos adversos , Quimioterapia de Indução , Análise de Intenção de Tratamento , Quimioterapia de Manutenção , Masculino , Oxidiazóis/efeitos adversos , Moduladores do Receptor de Esfingosina 1 Fosfato/efeitos adversosRESUMO
INTRODUCTION: Risk stratification is an important aspect of COVID-19 management, especially in patients admitted to ICU as it can provide more useful consumption of health resources, as well as prioritize critical care services in situations of overwhelming number of patients. MATERIALS AND METHODS: A multivariable predictive model for mortality was developed using data solely from a derivation cohort of 160 COVID-19 patients with moderate to severe ARDS admitted to ICU. The regression coefficients from the final multivariate model of the derivation study were used to assign points for the risk model, consisted of all significant variables from the multivariate analysis and age as a known risk factor for COVID-19 patient mortality. The newly developed AIDA score was arrived at by assigning 5 points for serum albumin and 1 point for IL-6, D dimer, and age. The score was further validated on a cohort of 304 patients admitted to ICU due to the severe form of COVID-19. RESULTS: The study population included 160 COVID-19 patients admitted to ICU in the derivation and 304 in the validation cohort. The mean patient age was 66.7 years (range, 20-93 years), with 68.1% men and 31.9% women. Most patients (76.8%) had comorbidities with hypertension (67.7%), diabetes (31.7), and coronary artery disease (19.3) as the most frequent. A total of 316 patients (68.3%) were treated with mechanical ventilation. Ninety-six (60.0%) in the derivation cohort and 221 (72.7%) patients in the validation cohort had a lethal outcome. The population was divided into the following risk categories for mortality based on the risk model score: low risk (score 0-1) and at-risk (score > 1). In addition, patients were considered at high risk with a risk score > 2. By applying the risk model to the validation cohort (n = 304), the positive predictive value was 78.8% (95% CI 75.5% to 81.8%); the negative predictive value was 46.6% (95% CI 37.3% to 56.2%); the sensitivity was 82.4% (95% CI 76.7% to 87.1%), and the specificity was 41.0% (95% CI 30.3% to 52.3%). The C statistic was 0.863 (95% CI 0.805-0.921) and 0.665 (95% CI 0.598-0.732) in the derivation and validation cohorts, respectively, indicating a high discriminative value of the proposed score. CONCLUSION: In the present study, AIDA score showed a valuable significance in estimating the mortality risk in patients with the severe form of COVID-19 disease at admission to ICU. Further external validation on a larger group of patients is needed to provide more insights into the utility of this score in everyday practice.
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COVID-19 , Hospitalização , Unidades de Terapia Intensiva , Modelos Biológicos , Oxigênio , Respiração Artificial , SARS-CoV-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/mortalidade , COVID-19/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/administração & dosagem , Oxigênio/sangue , Medição de RiscoRESUMO
Ultrashort laser pulse filamentation in air can extend the delivery of focused laser energy to distances greatly exceeding the Rayleigh length. In this way, remote measurements can be conducted using many standard methods of analytical spectroscopy. The performance of spectroscopic techniques can be enhanced by temporal gating, which rejects the unwanted noise and background. In the present work, we investigate the thermal relaxation of air in the wake of single-filament plasmas using shadowgraphy. We demonstrate that the transient change in refractive index associated with relaxation of the gas can be used to reject both continuous and time-varying spectroscopic signals, including emission from laser-produced plasmas. This method can augment temporal gating of simple optical detectors.