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1.
Space Sci Rev ; 219(5): 37, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448777

RESUMO

We review comprehensive observations of electromagnetic ion cyclotron (EMIC) wave-driven energetic electron precipitation using data collected by the energetic electron detector on the Electron Losses and Fields InvestigatioN (ELFIN) mission, two polar-orbiting low-altitude spinning CubeSats, measuring 50-5000 keV electrons with good pitch-angle and energy resolution. EMIC wave-driven precipitation exhibits a distinct signature in energy-spectrograms of the precipitating-to-trapped flux ratio: peaks at >0.5 MeV which are abrupt (bursty) (lasting ∼17 s, or ΔL∼0.56) with significant substructure (occasionally down to sub-second timescale). We attribute the bursty nature of the precipitation to the spatial extent and structuredness of the wave field at the equator. Multiple ELFIN passes over the same MLT sector allow us to study the spatial and temporal evolution of the EMIC wave - electron interaction region. Case studies employing conjugate ground-based or equatorial observations of the EMIC waves reveal that the energy of moderate and strong precipitation at ELFIN approximately agrees with theoretical expectations for cyclotron resonant interactions in a cold plasma. Using multiple years of ELFIN data uniformly distributed in local time, we assemble a statistical database of ∼50 events of strong EMIC wave-driven precipitation. Most reside at L∼5-7 at dusk, while a smaller subset exists at L∼8-12 at post-midnight. The energies of the peak-precipitation ratio and of the half-peak precipitation ratio (our proxy for the minimum resonance energy) exhibit an L-shell dependence in good agreement with theoretical estimates based on prior statistical observations of EMIC wave power spectra. The precipitation ratio's spectral shape for the most intense events has an exponential falloff away from the peak (i.e., on either side of ∼1.45 MeV). It too agrees well with quasi-linear diffusion theory based on prior statistics of wave spectra. It should be noted though that this diffusive treatment likely includes effects from nonlinear resonant interactions (especially at high energies) and nonresonant effects from sharp wave packet edges (at low energies). Sub-MeV electron precipitation observed concurrently with strong EMIC wave-driven >1 MeV precipitation has a spectral shape that is consistent with efficient pitch-angle scattering down to ∼ 200-300 keV by much less intense higher frequency EMIC waves at dusk (where such waves are most frequent). At ∼100 keV, whistler-mode chorus may be implicated in concurrent precipitation. These results confirm the critical role of EMIC waves in driving relativistic electron losses. Nonlinear effects may abound and require further investigation.

2.
Phys Rev E ; 107(5-2): 055006, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37328972

RESUMO

In this paper, two improvements to the theory of transition from brittle to ductile fracture developed by Langer [J. S. Langer, Phys. Rev. E 103, 063004 (2021)2470-004510.1103/PhysRevE.103.063004] are proposed. First, considering the drastic temperature rise near the crack tip, the temperature dependence of the shear modulus is included to better quantify the thermally sensitive dislocation entanglement. Second, the parameters of the improved theory are identified by the large-scale least-squares method. The comparison between the fracture toughness predicted by the theory and the values obtained in Gumbsch's experiments for tungsten at different temperatures [P. Gumbsch et al., Science 282, 1293 (1998)10.1126/science.282.5392.1293] shows good agreement.


Assuntos
Temperatura , Resistência à Tração
3.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(9): 1408-1414, 2022 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-36117347

RESUMO

Objective: To examine the prevalence and trend of tobacco and e-cigarettes uses and identify the influencing factors for smoking behavior in junior middle school students in Shanghai, and provide data support and scientific basis for the development of tobacco control intervention strategy in adolescents. Methods: Multi-stage stratified random sampling method was used to select junior middle school students in 8 districts and 10 districts in Shanghai in 2013 and in 2019 respectively. Information about tobacco and e-cigarettes uses in the students were collected by using self-administrated questionnaire. The prevalence of tobacco and e-cigarettes uses were calculated, the difference between two years was compared with χ2 test. The influencing factors were identified by multivariate logistic regression analysis. Results: In 2019, the current smoking rate was 0.6% in junior middle school students in Shanghai, and the smoking attempt rate was 2.9%, both were lower than the levels in 2013 (0.7% and 6.9%). The current use rate of e-cigarettes was 0.6% in 2019,with no significant change compared with 2013 (0.6%). The proportion of the students who had heard of e-cigarettes in 2019 (78.4%) was higher than that in 2013 (47.2%). In 2019, the second-hand smoke (SHS) exposure rate at home, in both indoor and outdoor public places and on public transportations was 72.5%, which was slightly lower than the level in 2013 (73.0%), the differences were all significant (P<0.05). In 2019, the students seeing close friend smoking (OR=27.381, 95%CI: 12.037-62.287), seeing someone smoking in school (OR=2.477, 95%CI: 1.155-5.312), believing that SHS may not be harmful (OR=8.471, 95%CI: 1.464-49.005) had higher possibility of smoking. Being aged ≥15 years (compared with being aged ≤12 years, OR=8.688, 95%CI: 1.922-39.266), exposure to SHS in outdoor public place (OR=8.608, 95%CI: 1.048-70.692), close friend smoking (OR=8.115, 95%CI: 1.754-37.545) were positively associated with e-cigarettes use, and believing that smoking results in uncomfortable social contact [compared with believing that smoking results in comfortable social contact (OR=0.105,95%CI: 0.018-0.615)] were negatively associated with e-cigarettes use, the difference was significant (P<0.05). Conclusion: The prevalence of tobacco and e-cigarette uses in junior middle school students in Shanghai remained at a low level in recent years. The SHS exposure rate in junior middle school students is high. Smoking behavior of junior middle school students is closely related to personal attitude and awareness of tobacco, exposure to SHS, peer smoking and the situation of tobacco control in schools. Prevention and intervention should be carried out from multi-dimensions to effectively protect teenagers from tobacco hazards.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Poluição por Fumaça de Tabaco , Adolescente , China/epidemiologia , Humanos , Prevalência , Estudantes , Nicotiana
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 55(12): 1482-1485, 2021 Dec 06.
Artigo em Chinês | MEDLINE | ID: mdl-34963247

RESUMO

This study was conducted between November to December 2020, consisting of six representative cities, Beijing, Shanghai, Shenzhen (with comprehensive smoke-free legislation), and Changsha, Chongqing, Shenyang (without comprehensive smoke-free legislation), 678 subjects were enrolled eventually, the mean age of the 678 subjects was (35.61±12.91)years old. Subjects from cities with comprehensive smoke-free legislation accounted for 49.71% of the total; male subjects accounted for 19.47%; meanwhile subjects from large, medium, and small restaurants accounted for 13.57% (92), 37.32% (253) and 49.11% (333) respectively. The analysis results indicate that the positive rate of restaurants staff of cotinine and 3'-hydroxynicotinine was lower in cities with comprehensive smoke-free legislation(34.12% vs 68.04%, χ²=78.01, P<0.001; 16.32% vs 41.94%, χ²=53.79, P<0.001), with staff from cities with comprehensive smoke-free legislation have lower concentrations of cotinine and 3'-hydroxynicotinine than their counterparts from cities without comprehensive smoke-free legislation(0.250 ng/ml vs 0.742 ng/ml, P<0.001; 0.250 ng/ml vs 0.250 ng/ml, P<0.001). No statistically significant difference in the concentration of cotinine and 3'-hydroxynicotinine in saliva between staff from restaurants of different sizes was detected (P>0.05).


Assuntos
Cotinina , Poluição por Fumaça de Tabaco , Adulto , China , Cidades , Cotinina/análise , Humanos , Masculino , Pessoa de Meia-Idade , Restaurantes , Saliva/química , Adulto Jovem
5.
J Aerosol Sci ; 155: 105766, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33897001

RESUMO

The 2020 coronavirus pandemic and the following quarantine measures have led to significant changes in daily life worldwide. Preliminary research indicates that air quality has improved in many urban areas as a result of these measures. This study takes a neighborhood-scale approach to quantifying this change in pollution. Using data from a network of citizen-hosted, low-cost particulate matter (PM) sensors, called Air Quality & yoU (AQ&U), we obtained high-spatial resolution measurements compared to the relatively sparse state monitoring stations. We compared monthly average estimated PM2.5 concentrations from February 11 to May 11, 2019 at 71 unique locations in Salt Lake County, UT, USA with the same (71) sensors' measurements during the same timeframe in 2020. A paired t-test showed significant reductions (71.1% and 21.3%) in estimated monthly PM2.5 concentrations from 2019 to 2020 for the periods from March 11-April 10 and April 11-May 10, respectively. The March time period corresponded to the most stringent COVID-19 related restrictions in this region. Significant decreases in PM2.5 were also reported by state monitoring sites during March (p < 0.001 compared to the previous 5-year average). While we observed decreases in PM2.5 concentrations across the valley in 2020, it is important to note that the PM2.5 concentrations did not improve equally in all locations. We observed the greatest reductions at lower elevation, more urbanized areas, likely because of the already low levels of PM2.5 at the higher elevation, more residential areas, which were generally below 2 µg/m3 in both 2019 and 2020. Although many of measurements during March and April were near or below the estimated detection limit of the low-cost PM sensors and the federal equivalent measurements, every low-cost sensor (51) showed a reduction in PM2.5 concentration in March of 2020 compared to 2019. These results suggest that the air quality improvement seen after March 11, 2020 is due to quarantine measures reducing traffic and decreasing pollutant emissions in the region.

6.
Appl Physiol Nutr Metab ; 46(2): 169-177, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32846097

RESUMO

Kgengwe fruits are commonly consumed in sub-Saharan countries. Recent reports indicated low coronary artery disease rates in those regions. To investigate anti-atherogenic properties and potential mechanisms of action of Kgengwe seed powder (KSP), male low-density lipoprotein receptor knockout (LDL-r-KO) mice were fed with an atherogenic diet supplemented with (treated, n = 10) or without (controls, n = 10) 10% (w/w) KSP for 20 weeks. Proximate analysis revealed that KSP contained 38% fibre and 15% lipids. KSP supplementation was not associated with significant changes in body weight gain rate, food intake, and plasma lipid levels. However, the average atherosclerotic lesion size in the aortic roots in the KSP-treated group was 58% smaller than that in the control group (0.26 vs 0.11 mm2, p < 0.05). This strong anti-atherogenic effect was associated with significant increases in the average plasma levels of certain cytokines such as IL-10 (6 vs 13 pg/mL, p < 0.05), GM-CSF (0.1 vs 0.2 pg/mL, p < 0.05), and EPO (7 vs 16 pg/mL, p < 0.05) along with reductions in the average levels of plasma MCP-1 (19 vs 14 pg/mL, p < 0.05) and MIP-2 (28 vs 13 pg/mL, p < 0.05). Except for relatively high levels of saturated fatty acids, KSP possesses balanced nutrient compositions with strong anti-atherogenic properties, which may be mediated through alterations in inflammatory pathways. Additional studies warrant confirmation and mechanism(s) of action of such effects. Novelty: Kgengwe seeds prevent atherogenesis in LDL-r-KO mice. Kgengwe seeds increase circulating levels of IL-10 and EPO. No reduction in plasma total cholesterol levels.


Assuntos
Aterosclerose/prevenção & controle , Citrullus , Placa Aterosclerótica/prevenção & controle , Sementes , Animais , Aterosclerose/sangue , Peso Corporal , Colesterol/sangue , Citrullus/química , Citocinas/sangue , Modelos Animais de Doenças , Ingestão de Alimentos , Ácidos Graxos/análise , Inflamação/prevenção & controle , Masculino , Camundongos Knockout , Tamanho do Órgão , Placa Aterosclerótica/sangue , Placa Aterosclerótica/patologia , Pós , Receptores de LDL , Triglicerídeos/sangue
7.
Proc Natl Acad Sci U S A ; 117(47): 29431-29434, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33168714

RESUMO

The thermodynamic dislocation theory (TDT) is based on two highly unconventional assumptions: first, that driven systems containing large numbers of dislocations are subject to the second law of thermodynamics and second, that the controlling inverse timescale for these systems is the thermally activated rate at which entangled pairs of dislocations become unpinned from each other. Here, we show that these two assumptions predict a scaling relation for steady-state stress as a function of strain rate and that this relation is accurately obeyed over a wide range of experimental data for aluminum and copper. This scaling relation poses a stringent test for the validity of the TDT. The fact that the TDT passes this test means that a wide range of problems in solid mechanics, previously thought to be fundamentally intractable, can now be addressed with confidence.

8.
Infect Control Hosp Epidemiol ; 41(8): 943-945, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32317037

RESUMO

Residents living in long-term care facilities (LTCFs) are at high risk of contracting healthcare-associated infections (HAIs). The unique operational and cultural characteristics of LTCFs and the currently evolving models of healthcare delivery in Scotland create great challenges for infection prevention and control (IPC). Existing literature that discusses the challenges of infection control in LTCFs focuses on operational factors within a facility and does not explore the challenges associated with higher levels of management and the lack of evidence to support IPC practices in this setting.1-7 Here, we provide a broader view of challenges faced by LTCFs in the context of the current health and social care models in Scotland. Many of these challenges are also faced in the rest of the United Kingdom and internationally.


Assuntos
Infecção Hospitalar , Assistência de Longa Duração , Infecção Hospitalar/prevenção & controle , Instalações de Saúde , Humanos , Controle de Infecções , Escócia
9.
Ultrasound Obstet Gynecol ; 55(3): 339-347, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31432562

RESUMO

OBJECTIVE: To compare the cost-effectiveness of cervical pessary vs vaginal progesterone to prevent preterm birth and neonatal morbidity in women with twin pregnancy and a short cervix. METHODS: Between 4 March 2016 and 3 June 2017, we performed this economic analysis following a randomized controlled trial (RCT), performed at My Duc Hospital, Ho Chi Minh City, Vietnam, that compared cervical pessary to vaginal progesterone in women with twin pregnancy and cervical length < 38 mm between 16 and 22 weeks of gestation. We used morbidity-free neonatal survival as a measure of effectiveness. Data on pregnancy outcome, maternal morbidity and neonatal complications were collected prospectively from medical files; additional information was obtained via telephone interviews with the patients. The incremental cost-effectiveness ratio was calculated as the incremental cost required to achieve one extra surviving morbidity-free neonate in the pessary group compared with in the progesterone group. Probabilistic and one-way sensitivity analyses were also performed. RESULTS: During the study period, we screened 1113 women with twin pregnancy, of whom 300 fulfilled the inclusion criteria of the RCT and gave informed consent to participate. These women were assigned randomly to receive cervical pessary (n = 150) or vaginal progesterone (n = 150), with two women and one woman, respectively, being lost to follow-up. The rate of morbidity-free neonatal survival was significantly higher in the pessary group compared with the progesterone group (n = 241/296 (81.4%) vs 219/298 (73.5%); relative risk, 1.11 (95% CI, 1.02-1.21), P = 0.02). The mean total cost per woman was 3146 € in the pessary group vs 3570 € in the progesterone group (absolute difference, -424 € (95% CI, -842 to -3 €), P = 0.048). The cost per morbidity-free neonate was significantly lower in the pessary group compared with that in the progesterone group (2492 vs 2639 €; absolute difference, -147 € (95% CI, -284 to 10 €), P = 0.035). CONCLUSION: In women with twin pregnancy and a short cervix, cervical pessary improves significantly the rate of morbidity-free neonatal survival while reducing costs, as compared with vaginal progesterone. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Pessários/economia , Resultado da Gravidez/economia , Nascimento Prematuro/prevenção & controle , Progesterona/economia , Incompetência do Colo do Útero/terapia , Administração Intravaginal , Adulto , Medida do Comprimento Cervical , Colo do Útero/patologia , Análise Custo-Benefício , Feminino , Humanos , Gravidez , Gravidez de Gêmeos , Nascimento Prematuro/economia , Progesterona/administração & dosagem , Resultado do Tratamento , Incompetência do Colo do Útero/economia
10.
NPJ Parkinsons Dis ; 4: 30, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30302391

RESUMO

Increasing evidence suggests that environmental neurotoxicants or misfolded α-synuclein generated by such neurotoxicants are transported from the gastrointestinal tract to the central nervous system via the vagus nerve, triggering degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and causing Parkinson's disease (PD). We tested the hypothesis that gastric co-administration of subthreshold doses of lectins and paraquat can recreate the pathology and behavioral manifestations of PD in rats. A solution containing paraquat + lectin was administered daily for 7 days via gastric gavage, followed by testing for Parkinsonian behavior and gastric dysmotility. At the end of the experiment, brainstem and midbrain tissues were analyzed for the presence of misfolded α-synuclein and neuronal loss in the SNpc and in the dorsal motor nucleus of the vagus (DMV). Misfolded α-synuclein was found in DMV and SNpc neurons. A significant decrease in tyrosine hydroxylase positive dopaminergic neurons was noted in the SNpc, conversely there was no apparent loss of cholinergic neurons of the DMV. Nigrovagally-evoked gastric motility was impaired in treated rats prior to the onset of parkinsonism, the motor deficits of which were improved by l-dopa treatment. Vagotomy prevented the development of parkinsonian symptoms and constrained the appearance of misfolded α-synuclein to myenteric neurons. These data demonstrate that co-administration of subthreshold doses of paraquat and lectin induces progressive, l-dopa-responsive parkinsonism that is preceded by gastric dysmotility. This novel preclinical model of environmentally triggered PD provides functional support for Braak's staging hypothesis of idiopathic PD.

11.
Phys Rev E ; 97(4-1): 043002, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29758656

RESUMO

The thermodynamic dislocation theory developed for nonuniform plastic deformations is used here to simulate the stress-strain curves for crystals subjected to antiplane shear-controlled load reversal. We show that the presence of the positive back stress during the load reversal reduces the magnitude of shear stress required to pull excess dislocations back to the center of the specimen. There, the excess dislocations of opposite signs meet and annihilate each other leading to the Bauschinger effect.

12.
Pediatr Obes ; 13(4): 204-212, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28960843

RESUMO

BACKGROUND: Intakes of dietary sugars is a global concern, and many national and international organizations have set targets to limit consumption. However, it is unclear to what extent intakes of total and added sugars vary between geographies. OBJECTIVES: The aim of this study was to assess the differences in intakes of total and added sugars in 4 to 13-year-old children in China, Mexico and the United States. The secondary aim was to identify main sources of total and added sugars in the diets of these children. METHODS: Secondary data analysis was conducted using the 2011 China Health and Nutrition Survey, 2012 Mexican National Health and Nutrition Survey, and 2009-2012 US National Health and Nutrition Examination Surveys. Total and added sugar intakes were calculated using the US Food Patterns Equivalents Database. RESULTS: Mean intakes of total and added sugars were 26 and 9 g d-1 among Chinese children, 92 and 55 g d-1 among Mexican children, and 124 and 76 g d-1 among US children, respectively. The top food sources of total sugars were fruits among Chinese children, and sugar-sweetened beverages and milk-based beverages among Mexican and US children. CONCLUSIONS: These data highlight the heterogeneity of food patterns worldwide and the need for adapted country-specific public health recommendations on sugars.


Assuntos
Açúcares da Dieta/administração & dosagem , Inquéritos Nutricionais , Adolescente , Animais , Bebidas/análise , Criança , Pré-Escolar , China , Dieta , Açúcares da Dieta/efeitos adversos , Ingestão de Energia , Feminino , Frutas/química , Humanos , Masculino , México , Leite/química , Açúcares/análise , Edulcorantes/administração & dosagem , Estados Unidos
13.
Clin Nucl Med ; 43(1): 44-45, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29076916

RESUMO

A 64-year-old man with a history of metastatic clear cell renal cell cancer was referred for progress Ga-DOTATATE PET/CT imaging. Ga-DOTATATE PET/CT imaging demonstrated increased DOTATATE uptake (SUVmax 13.8) in the left thigh localized to a soft tissue lesion. Cytopathology of the resected lesion was in keeping with a clear cell renal cell cancer metastasis. This case illustrates that Ga-DOTATATE accumulation in a soft tissue lesion can be due to a clear cell renal cell cancer metastasis.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Compostos Organometálicos/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/secundário , Transporte Biológico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecidos Moles/metabolismo
14.
Clin Nucl Med ; 42(11): 881-884, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28902734

RESUMO

A 66-year-old man with history of prostate carcinoma underwent Ga-labeled prostate-specific membrane antigen PET/CT for surveillance of rising prostate-specific antigen. Intense tracer uptake was noted in segments 2, 7, and 8 of the liver. The lesions were not FDG avid on F-FDG PET/CT. Further characterization with magnetic resonance cholangiopancreatography with Gd-EOB (Primovist) contrast revealed ill-defined arterially enhancing lesions with central washout in the venous phase. CT-guided core biopsy was performed, and histopathology confirmed well-differentiated hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Radioisótopos de Gálio , Achados Incidentais , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Antígeno Prostático Específico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade
15.
Phys Rev E ; 96(1-1): 013004, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29347159

RESUMO

The statistical-thermodynamic dislocation theory developed in previous papers is used here in an analysis of high-temperature deformation of aluminum and steel. Using physics-based parameters that we expect theoretically to be independent of strain rate and temperature, we are able to fit experimental stress-strain curves for three different strain rates and three different temperatures for each of these two materials. Our theoretical curves include yielding transitions at zero strain in agreement with experiment. We find that thermal softening effects are important even at the lowest temperatures and smallest strain rates.

16.
Chem Sci ; 7(7): 4308-4317, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30155077

RESUMO

Magnetic resonance imaging (MRI) is a preferred technique for noninvasively monitoring the fate of implanted cells, such as stem cells and immune cells in vivo. Cellular MRI requires contrast agents (CAs) to label the cells of interest. Despite promising progress made in this emerging field, highly sensitive, stable and biocompatible T1 CAs with high cell permeability and specificity remains an unmet challenge. To address this need, a novel MnIII-porphyrin, MnAMP was designed and synthesized based on the modification of MnIIItetra(carboxy-porphyrin) (MnTCP), a small and highly stable non-Gd extracellular CA with good biocompatibility and high T1 relaxivity (r1 = 7.9 mM-1 s-1) at clinical field of 3 Tesla (T). Cell permeability was achieved by masking the polar carboxylates of MnTCP with acetoxymethyl-ester (AM) groups, which are susceptible to hydrolysis by intracellular esterases. The enzymatic cleavage of AM groups led to disaggregation of the hydrophobic MnAMP, releasing activated MnTCP with significant increase in T1 relaxivity. Cell uptake of MnAMP is highly efficient as tested on two non-phagocytic human cell lines with no side effects observed on cell viability. MRI of labeled cells exhibited significant contrast enhancement with a short T1 of 161 ms at 3 T, even though a relatively low concentration of MnAMP and short incubation time was applied for cell labeling. Overall, MnAMP is among the most efficient T1 cell labeling agents developed for cellular MRI.

17.
CPT Pharmacometrics Syst Pharmacol ; 4(10): 595-604, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26535160

RESUMO

Intravitreally administered lampalizumab is an investigational complement inhibitor directed against complement factor D (CFD) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration. We sought to develop an integrated ocular and systemic pharmacokinetic/pharmacodynamic model for lampalizumab in patients with GA using the data from the clinical phase I and II studies. The kinetics of lampalizumab and CFD disposition were well described by the combined ocular/serum target-mediated drug disposition model using a quasi-steady-state approximation. This model takes into account the drug, target, and drug-target complex clearance, their transfer rates between ocular and serum compartments, and turnover kinetics of CFD. The constructed model provided a prediction of target occupancy in ocular tissues and supported that the two dosing regimens (10 mg q4w and 10 mg q6w) selected for the phase III studies are expected to be efficacious and able to achieve near-complete target engagement in the vitreous humor.

18.
J Magn Reson Imaging ; 41(2): 397-403, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24399613

RESUMO

PURPOSE: To evaluate a new formulation of manganese porphyrin as a potential gadolinium (Gd)-free extracellular magnetic resonance imaging (MRI) contrast agent for dynamic contrast-enhanced (DCE) MRI of tumors. MATERIALS AND METHODS: A previously reported new contrast agent, MnTCP, was evaluated in six female tumor-bearing nude rats. MRI was performed on a 3 T clinical scanner 3 to 4 weeks after inoculation of breast tumor cells in the mammary fat pads. Gd-DTPA was injected intravenously, followed by injection of MnTCP at least 2 hours later (both at 0.05 mmol/kg). T1 relaxation time measurements and DCE-MRI were performed. RESULTS: Enhancement and clearance patterns were visually similar between MnTCP and Gd-DTPA. However, relative R1 increases in all 11 tumors were larger for MnTCP over 60 minutes postcontrast, the difference being significant as late as 20 minutes (R1post /R1pre = 1.42 ± 0.15 for MnTCP vs. 1.20 ± 0.08 for Gd-DTPA, P < 0.05). R1 -related effects for MnTCP were largely reduced after 60 minutes (R1post /R1pre = 1.13 ± 0.07) and completely gone within 24 hours (R1post /R1pre = 0.97 ± 0.06). DCE-MRI revealed a consistently larger (1.5 to over 2-fold) peak enhancement and higher values of the steepest slope, time-to-peak, and AUC60 in all tumors with MnTCP (P < 0.01). CONCLUSION: MnTCP is an alternative to extracellular Gd agents for tumor imaging, offering sensitive detection and rapid renal clearance.


Assuntos
Meios de Contraste , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Mamárias Experimentais/patologia , Manganês , Porfirinas , Animais , Feminino , Gadolínio DTPA , Ratos , Ratos Nus
19.
Ann Fr Anesth Reanim ; 33(3): e35-41, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24378044

RESUMO

OBJECTIVE: Intraoperative haemodynamic optimization based on fluid management and stroke volume optimization (Goal Directed Fluid Therapy [GDFT]) can improve patients' postoperative outcome. We have described a closed-loop fluid management system based on stroke volume variation and stroke volume monitoring. The goal of this system is to apply GDFT protocols automatically. After conducting simulation, engineering, and animal studies the present report describes the first use of this system in the clinical setting. STUDY DESIGN: Prospective pilot study. PATIENTS: Patients undergoing major surgery. METHODS: Twelve patients at two institutions had intraoperative GDFT delivered by closed-loop controller under the direction of an anaesthesiologist. Compliance with GDFT management was defined as acceptable when a patient spent more than 85% of the surgery time in a preload independent state (defined as stroke volume variation<13%), or when average cardiac index during the case was superior or equal to 2.5l/min/m(2). RESULTS: Closed-loop GDFT was completed in 12 patients. Median surgery time was 447 [309-483] min and blood loss was 200 [100-1000] ml. Average cardiac index was 3.2±0.8l/min/m(2) and on average patients spent 91% (76 to 100%) of the surgery time in a preload independent state. Twelve of 12 patients met the criteria for compliance with intraoperative GDFT management. CONCLUSION: Intraoperative GDFT delivered by closed-loop system under anaesthesiologist guidance allowed to obtain targeted objectives in 91% of surgery time. This approach may provide a way to ensure consistent high-quality delivery of fluid administration and compliance with perioperative goal directed therapy.


Assuntos
Hidratação/métodos , Cuidados Intraoperatórios/métodos , Idoso , Idoso de 80 Anos ou mais , Anestesia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Ponte de Artéria Coronária , Feminino , Hidratação/instrumentação , Objetivos , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Projetos Piloto , Estudos Prospectivos , Volume Sistólico , Procedimentos Cirúrgicos Operatórios/métodos
20.
Obesity (Silver Spring) ; 21(4): 782-5, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23512506

RESUMO

OBJECTIVE: To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short-term overfeeding in healthy subjects. DESIGN AND METHODS: The analysis of the data collected in several studies in which fasting hepatic glucose production (HGP), hepatic insulin sensitivity index (HISI), and intrahepatocellular lipids (IHCL) had been measured after both 6-7 days on a weight-maintenance diet (control, C; n = 55) and 6-7 days of overfeeding with 1.5 (F1.5, n = 7), 3 (F3, n = 17), or 4 g fructose/kg/day (F4, n = 10), with 3 g glucose/kg/day (G3, n = 11), or with 30% excess energy as saturated fat (fat30%, n = 10). RESULTS: F3, F4, G3, and fat30% all significantly increased IHCL, respectively by 113 ± 86, 102 ± 115, 59 ± 92, and 90 ± 74% as compared to C (all P < 0.05). F4 and G3 increased HGP by 16 ± 10 and 8 ± 11% (both P < 0.05), and F3 and F4 significantly decreased HISI by 20 ± 22 and 19 ± 14% (both P < 0.01). In contrast, there was no significant effect of fat30% on HGP or HISI. CONCLUSIONS: Short-term overfeeding with fructose or glucose decreases hepatic insulin sensitivity and increases hepatic fat content. This indicates short-term regulation of hepatic glucose metabolism by simple carbohydrates.


Assuntos
Frutose/administração & dosagem , Glucose/administração & dosagem , Resistência à Insulina , Fígado/efeitos dos fármacos , Glicemia/análise , Índice de Massa Corporal , Dieta , Ingestão de Energia , Jejum , Ácidos Graxos/administração & dosagem , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Adulto Jovem
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