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1.
J Emerg Med ; 56(3): 308-318, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30711368

RESUMO

BACKGROUND: Recent-onset atrial fibrillation (RAF) is the most frequent supraventricular dysrhythmia in emergency medicine. Severely compromised patients require acute treatment with injectable drugs OBJECTIVE: The main purpose of this external validity study was to compare the short-term efficacy of esmolol with that of amiodarone to treat severe RAF in an emergency setting. METHODS: This retrospective survey was conducted in mobile intensive care units by analyzing patient records between 2002 and 2013. We included RAF with (one or more) severity factors including: clinical shock, angina pectoris, ST shift, and very rapid ventricular rate. A blind matching procedure was used to constitute esmolol group (n = 100) and amiodarone group (n = 200), with similar profiles for age, gender, initial blood pressure, heart rate, severity factors, and treatment delay. The main outcome measure was the percentage of patients with a ventricular rate control defined as heart frequency ≤ 100 beats/min. More stringent (rhythm control) and more humble indicators (20% heart rate reduction) were analyzed at from 10 to 120 min after treatment initiation. RESULTS: Patient characteristics were comparable for both groups: age 66 ± 16 years, male 71%, treatment delay < 1 h 36%, 1-2 h 29%, > 2 h 35%, chest pain 61%, ST shift 62%, ventricular rate 154 ± 26 beats/min, and blood pressure 126/73 mm Hg. The superiority of esmolol was significant at 40 min (64% rate control with esmolol vs. 25% with amiodarone) and for all indicators from 10 to 120 min after treatment onset. CONCLUSION: In "real life emergency medicine," esmolol is better than amiodarone in the treatment of RAF.


Assuntos
Amiodarona/normas , Fibrilação Atrial/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Propanolaminas/normas , Antagonistas de Receptores Adrenérgicos beta 1/normas , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Amiodarona/uso terapêutico , Antiarrítmicos/normas , Antiarrítmicos/uso terapêutico , Medicina de Emergência/métodos , Medicina de Emergência/normas , Serviço Hospitalar de Emergência/organização & administração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propanolaminas/uso terapêutico , Estudos Retrospectivos , Inquéritos e Questionários , Fatores de Tempo
2.
Neurotoxicology ; 69: 152-163, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30312642

RESUMO

The globally used herbicide glufosinate-ammonium (GLA) is structurally analogous to the excitatory neurotransmitter glutamate, and is known to interfere with cellular mechanisms involved in the glutamatergic system. In this report, we used an in vitro model of murine primary neural stem cell culture to investigate the neurotoxicity of GLA and its main metabolite, 4-methylphosphinico-2-oxobutanoic acid (PPO). We demonstrated that GLA and PPO disturb ependymal wall integrity in the ventricular-subventricular zone (V-SVZ) and alter the neuro-glial differentiation of neural stem cells. GLA and PPO impaired the formation of cilia, with reduced Celsr2 expression after PPO exposure. GLA promoted the differentiation of neuronal and oligodendroglial cells while PPO increased B1 cell population and impaired neuronal fate of neural stem cells. These results confirm our previous in vivo report that developmental exposure to GLA alters neurogenesis in the SVZ, and neuroblast migration along the rostral migratory stream. They also highlight the importance of investigating the toxicity of pesticide degradation products. Indeed, not only GLA, but also its metabolite PPO disrupts V-SVZ homeostasis and provides a novel cellular mechanism underlying GLA-induced neurodevelopmental toxicity. Furthermore, we were able to demonstrate a neurotoxic activity of a metabolite of GLA different from that of GLA active substance for the very first time.


Assuntos
Aminobutiratos/toxicidade , Herbicidas/toxicidade , Ventrículos Laterais/citologia , Ventrículos Laterais/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Aminobutiratos/metabolismo , Animais , Animais Recém-Nascidos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Herbicidas/metabolismo , Ventrículos Laterais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/metabolismo , Prosencéfalo/citologia , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/metabolismo
3.
Seizure ; 61: 170-176, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30176574

RESUMO

PURPOSE: Few outcome data are available about morbidity associated with endotracheal intubation modalities in critically ill patients with convulsive status epilepticus. We compared etomidate versus sodium thiopental for emergency rapid sequence intubation in patients with out-of-hospital convulsive status epilepticus. METHODS: Patients admitted to our intensive care unit in 2006-2015 were studied retrospectively. The main outcome measure was seizure and/or status epilepticus recurrence within 12 h after rapid sequence intubation. RESULTS: We included 97 patients (60% male; median age, 59 years [IQR, 48-70]). Median time from seizure onset to first antiepileptic drug was 60 min [IQR, 35-90]. Reasons for intubation were coma in 95 (98%), acute respiratory distress in 18 (19%), refractory convulsive status epilepticus in 9 (9%), and shock in 6 (6%) patients; 50 (52%) patients had more than one reason. The hypnotic drugs used were etomidate in 54 (56%) and sodium thiopental in 43 (44%) patients. Seizure and/or status epilepticus recurred in 13 (56%) patients in the etomidate group and 11 patients (44%) in the sodium thiopental group (adjusted common odds ratio [aOR], 0.98; 95%CI, 0.36-2.63; P = 0.97). The two groups were not significantly different for proportions of patients with hemodynamic instability after intubation (aOR, 0.60; 95%CI, 0.23-1.58; P = 0.30) or with difficult endotracheal intubation (OR, 1.28; 95% CI 0.23 to 7.21; P=0.77). CONCLUSIONS: Our findings argue against a difference in seizure and/or status epilepticus recurrences rates between critically ill patients with convulsive status epilepticus given etomidate vs. sodium thiopental as the induction agent for emergency intubation.


Assuntos
Etomidato/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Intubação/métodos , Estado Epiléptico/terapia , Tiopental/uso terapêutico , Idoso , Resultados de Cuidados Críticos , Feminino , Escala de Coma de Glasgow , Hemodinâmica/efeitos dos fármacos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Estado Epiléptico/epidemiologia , Resultado do Tratamento
4.
JAMA ; 319(8): 779-787, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29486039

RESUMO

Importance: Bag-mask ventilation (BMV) is a less complex technique than endotracheal intubation (ETI) for airway management during the advanced cardiac life support phase of cardiopulmonary resuscitation of patients with out-of-hospital cardiorespiratory arrest. It has been reported as superior in terms of survival. Objectives: To assess noninferiority of BMV vs ETI for advanced airway management with regard to survival with favorable neurological function at day 28. Design, Settings, and Participants: Multicenter randomized clinical trial comparing BMV with ETI in 2043 patients with out-of-hospital cardiorespiratory arrest in France and Belgium. Enrollment occurred from March 9, 2015, to January 2, 2017, and follow-up ended January 26, 2017. Intervention: Participants were randomized to initial airway management with BMV (n = 1020) or ETI (n = 1023). Main Outcomes and Measures: The primary outcome was favorable neurological outcome at 28 days defined as cerebral performance category 1 or 2. A noninferiority margin of 1% was chosen. Secondary end points included rate of survival to hospital admission, rate of survival at day 28, rate of return of spontaneous circulation, and ETI and BMV difficulty or failure. Results: Among 2043 patients who were randomized (mean age, 64.7 years; 665 women [32%]), 2040 (99.8%) completed the trial. In the intention-to-treat population, favorable functional survival at day 28 was 44 of 1018 patients (4.3%) in the BMV group and 43 of 1022 patients (4.2%) in the ETI group (difference, 0.11% [1-sided 97.5% CI, -1.64% to infinity]; P for noninferiority = .11). Survival to hospital admission (294/1018 [28.9%] in the BMV group vs 333/1022 [32.6%] in the ETI group; difference, -3.7% [95% CI, -7.7% to 0.3%]) and global survival at day 28 (55/1018 [5.4%] in the BMV group vs 54/1022 [5.3%] in the ETI group; difference, 0.1% [95% CI, -1.8% to 2.1%]) were not significantly different. Complications included difficult airway management (186/1027 [18.1%] in the BMV group vs 134/996 [13.4%] in the ETI group; difference, 4.7% [95% CI, 1.5% to 7.9%]; P = .004), failure (69/1028 [6.7%] in the BMV group vs 21/996 [2.1%] in the ETI group; difference, 4.6% [95% CI, 2.8% to 6.4%]; P < .001), and regurgitation of gastric content (156/1027 [15.2%] in the BMV group vs 75/999 [7.5%] in the ETI group; difference, 7.7% [95% CI, 4.9% to 10.4%]; P < .001). Conclusions and Relevance: Among patients with out-of-hospital cardiorespiratory arrest, the use of BMV compared with ETI failed to demonstrate noninferiority or inferiority for survival with favorable 28-day neurological function, an inconclusive result. A determination of equivalence or superiority between these techniques requires further research. Trial Registration: clinicaltrials.gov Identifier: NCT02327026.


Assuntos
Suporte Vital Cardíaco Avançado/métodos , Intubação Intratraqueal , Máscaras Laríngeas , Parada Cardíaca Extra-Hospitalar/terapia , Idoso , Bélgica , Serviços Médicos de Emergência , Feminino , França , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Parada Cardíaca Extra-Hospitalar/complicações , Parada Cardíaca Extra-Hospitalar/mortalidade
5.
Stapp Car Crash J ; 62: 93-118, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30608994

RESUMO

In the last decade, extensive efforts have been made to understand the physics of submarining and its consequences in terms of abdominal injuries. For that purpose, 27 Post Mortem Human Subject (PMHS) tests were performed in well controlled conditions on a sled and response corridors were provided to assess the biofidelity of dummies or human body models. All these efforts were based on the 50th percentile male. In parallel, efforts were initiated to transfer the understanding of submarining and the prediction criteria to the THOR dummies. Both the biofidelity targets and the criteria were scaled down from the 50th percentile male to the 5th percentile THOR female. The objective of this project was to run a set of reference PMHS tests in order to check the biofidelity of the THOR F05 in terms of submarining. Three series of tests were performed on nine PMHS, the first one was designed to avoid submarining, the second and third ones were designed to result in submarining. In the first configuration, no submarining was observed in 3 cases out of 4 and only one iliac wing fracture occurred in one subject. In the second and third configurations, all subjects but one sustained submarining. In addition, two subjects out of three in the third configuration sustained substantial iliac wing fractures. Nevertheless, all configurations can be represented by at least one or several cases without any pelvis fracture. Corridors were constructed for the external forces and the PMHS kinematics. They are provided in this paper as new experimental references to assess the biofidelity of small female human surrogates in different configurations where submarining did or did not occur.


Assuntos
Acidentes de Trânsito , Fraturas da Coluna Vertebral , Fenômenos Biomecânicos , Cadáver , Feminino , Humanos , Masculino , Sujeitos da Pesquisa
6.
PLoS One ; 12(10): e0184475, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29020013

RESUMO

Accumulating evidence suggests that developmental exposure to environmental chemicals may modify the course of brain development, ultimately leading to neuropsychiatric / neurodegenerative disorders later in life. In the present study, we assessed the impact of one of the most frequently used pesticides in both residential and agricultural applications - the synthetic pyrethroid cypermethrin (CYP) - on developmental neurotoxicity (DNT). Female mice were perinatally exposed to low doses of CYP (5 and 20 mg/kg body weight) from gestation to postnatal day 15. Behavioral analyses were performed during the offspring's early life and during adulthood. Postnatal analyses revealed that perinatal exposure to CYP disturbed motor development without modifying sensory and communicative skills. We found that later in life, CYP-exposed offspring expressed maladaptive behaviors in response to highly challenging tasks and abnormal sociability. Transcriptomic analyses performed in the offspring's brain at the end of the exposure, highlighted mitochondrial dysfunction as a relevant pathomechanism underlying CYP-induced DNT. Interestingly, several genes involved in proteostasis maintenance were also shown to be dysregulated suggesting that alterations in biogenesis, folding, trafficking and degradation of proteins may significantly contribute to CYP-related DNT. From a regulatory perspective, this study highlights that behavioral and transcriptomic analyses are complementary tools providing useful direction for better DNT characterization, and as such, should be used together more systematically.


Assuntos
Etologia/métodos , Inseticidas/toxicidade , Lactação/efeitos dos fármacos , Transtornos do Neurodesenvolvimento/genética , Efeitos Tardios da Exposição Pré-Natal/genética , Piretrinas/toxicidade , Transcriptoma/genética , Animais , Animais Recém-Nascidos , Comportamento Animal , Encéfalo/crescimento & desenvolvimento , Cognição/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos CBA , Anotação de Sequência Molecular , Transtornos do Neurodesenvolvimento/patologia , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Comportamento Social , Estresse Fisiológico/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos
7.
Resuscitation ; 109: 49-55, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27743918

RESUMO

BACKGROUND: Obesity prevalence has dramatically increased over recent years and is associated with cardiovascular diseases, but data are lacking on its prognostic impact in out-of-hospital cardiac arrest (OHCA) patients. METHODS: Data of all consecutive OHCA patients admitted in two cardiac arrest centers from Paris and suburbs between 2005 and 2012 were prospectively collected. Patients treated by therapeutic hypothermia (TH) were included in the analysis. Logistic and Cox regression analyses were used to quantify the association between body mass index (BMI) at hospital admission and day-30 and 1-year mortality respectively. RESULTS: 818 patients were included in the study (median age 60.9 [50.8-72.7] year, 70.2% male). Obese patients (BMI>30kgm-2) were older, more frequently male and evidenced more frequently cardiovascular risk factors than normally (18.530kgm-2 was independently associated with day-30 mortality (Odds ratio [OR] in comparison with normally weight patients 2.45; 95% confidence interval [95%CI: 1.32-4.56; p<0.01]). Obesity was not associated with one-year mortality (Hazard ratio [HR] 0.99, 95%CI 0.21,4.67; p=0.99) while underweight was associated with one-year mortality in this subgroup of patients (Hazard ratio [HR] 3.94, 95%CI 1.11,14.01; p=0.03). CONCLUSION: In the present study, obesity was independently associated with day-30 mortality in successfully resuscitated ICU TH OHCA patients. Further studies are needed to understand the mechanisms that underpin this finding.


Assuntos
Índice de Massa Corporal , Hipotermia Induzida/efeitos adversos , Obesidade/mortalidade , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Idoso , Reanimação Cardiopulmonar , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
8.
Clin Sci (Lond) ; 130(21): 1939-54, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27549113

RESUMO

Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1ß (IL-1ß) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3× per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R-dependent pulmonary inflammation with airway hyperreactivity in mice.


Assuntos
Aminobutiratos/toxicidade , Ácido Glutâmico/imunologia , Herbicidas/toxicidade , Interleucina-1beta/imunologia , Pneumonia/imunologia , Receptores de Interleucina-1/imunologia , Receptores de N-Metil-D-Aspartato/metabolismo , Aminobutiratos/imunologia , Animais , Herbicidas/imunologia , Humanos , Interleucina-1beta/genética , Camundongos , Camundongos Endogâmicos C57BL , N-Metilaspartato , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Peroxidase/genética , Peroxidase/imunologia , Pneumonia/etiologia , Receptores de Interleucina-1/genética , Receptores de N-Metil-D-Aspartato/genética
9.
Front Cell Neurosci ; 10: 191, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27555806

RESUMO

Neurogenesis, a process of generating functional neurons from neural precursors, occurs throughout life in restricted brain regions such as the subventricular zone (SVZ). During this process, newly generated neurons migrate along the rostral migratory stream to the olfactory bulb to replace granule cells and periglomerular neurons. This neuronal migration is pivotal not only for neuronal plasticity but also for adapted olfactory based behaviors. Perturbation of this highly controlled system by exogenous chemicals has been associated with neurodevelopmental disorders. We reported recently that perinatal exposure to low dose herbicide glufosinate ammonium (GLA), leads to long lasting behavioral defects reminiscent of Autism Spectrum Disorder-like phenotype in the offspring (Laugeray et al., 2014). Herein, we demonstrate that perinatal exposure to low dose GLA induces alterations in neuroblast proliferation within the SVZ and abnormal migration from the SVZ to the olfactory bulbs. These disturbances are not only concomitant to changes in cell morphology, proliferation and apoptosis, but are also associated with transcriptomic changes. Therefore, we demonstrate for the first time that perinatal exposure to low dose GLA alters SVZ neurogenesis. Jointly with our previous work, the present results provide new evidence on the link between molecular and cellular consequences of early life exposure to the herbicide GLA and the onset of ASD-like phenotype later in life.

10.
J Am Coll Cardiol ; 68(1): 40-9, 2016 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-27364049

RESUMO

BACKGROUND: Preliminary data suggested a clinical benefit in treating out-of-hospital cardiac arrest (OHCA) patients with a high dose of erythropoietin (Epo) analogs. OBJECTIVES: The authors aimed to evaluate the efficacy of epoetin alfa treatment on the outcome of OHCA patients in a phase 3 trial. METHODS: The authors performed a multicenter, single-blind, randomized controlled trial. Patients still comatose after a witnessed OHCA of presumed cardiac origin were eligible. In the intervention group, patients received 5 intravenous injections spaced 12 h apart during the first 48 h (40,000 units each, resulting in a maximal dose of 200,000 total units), started as soon as possible after resuscitation. In the control group, patients received standard care without Epo. The main endpoint was the proportion of patients in each group reaching level 1 on the Cerebral Performance Category (CPC) scale (survival with no or minor neurological sequelae) at day 60. Secondary endpoints included all-cause mortality rate, distribution of patients in CPC levels at different time points, and side effects. RESULTS: In total, 476 patients were included in the primary analysis. Baseline characteristics were similar in the 2 groups. At day 60, 32.4% of patients (76 of 234) in the intervention group reached a CPC 1 level, as compared with 32.1% of patients (78 of 242) in the control group (odds ratio: 1.01; 95% confidence interval: 0.68 to 1.48). The mortality rate and proportion of patients in each CPC level did not differ at any time points. Serious adverse events were more frequent in Epo-treated patients as compared with controls (22.6% vs. 14.9%; p = 0.03), particularly thrombotic complications (12.4% vs. 5.8%; p = 0.01). CONCLUSIONS: In patients resuscitated from an OHCA of presumed cardiac cause, early administration of erythropoietin plus standard therapy did not confer a benefit, and was associated with a higher complication rate. (High Dose of Erythropoietin Analogue After Cardiac Arrest [Epo-ACR-02]; NCT00999583).


Assuntos
Epoetina alfa/administração & dosagem , Hematínicos/administração & dosagem , Parada Cardíaca Extra-Hospitalar/tratamento farmacológico , Idoso , Intervenção Médica Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego
11.
Neuroreport ; 27(7): 532-41, 2016 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-27031874

RESUMO

Glufosinate-ammonium (GLA), the active component of a widely used herbicide, induces convulsions in rodents and humans. In mouse, intraperitoneal treatment with 75 mg/kg GLA generates repetitive tonic-clonic seizures associated with 100% mortality within 72 h after treatment. In this context, we characterized GLA-induced seizures, their histological consequences and the effectiveness of diazepam treatment. Epileptic discharges on electroencephalographic recordings appeared simultaneously in the hippocampus and the cerebral cortex. Diazepam treatment at 6 h immediately stopped the seizures and prevented animal death. However, intermittent seizures were recorded on electroencephalogram from 6 h after diazepam treatment until 24 h, but had disappeared after 15 days. In our model, neuronal activation (c-Fos immunohistochemistry) was observed 6 h after GLA exposure in the dentate gyrus, CA1, CA3, amygdala, piriform and entorhinal cortices, indicating the activation of the limbic system. In these structures, Fluoro-Jade C and Cresyl violet staining did not show neuronal suffering. However, astroglial activation was clearly observed at 24 h and 15 days after GLA treatment in the amygdala, piriform and entorhinal cortices by PCR quantitative, western blot and immunohistochemistry. Concomitantly, glutamine synthetase mRNA expression (PCR quantitative), protein expression (western blot) and enzymatic activity were upregulated. In conclusion, our study suggests that GLA-induced seizures: (a) involved limbic structures and (b) induced astrocytosis without neuronal degeneration as an evidence of a reactive astrocyte beneficial effect for neuronal protection.


Assuntos
Aminobutiratos/toxicidade , Encéfalo/efeitos dos fármacos , Herbicidas/toxicidade , Organofosfatos/toxicidade , Convulsões/induzido quimicamente , Animais , Anticonvulsivantes/administração & dosagem , Astrócitos/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Diazepam/administração & dosagem , Eletroencefalografia , Glutamato-Amônia Ligase/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Convulsões/metabolismo , Convulsões/fisiopatologia
12.
Stapp Car Crash J ; 59: 203-23, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26660745

RESUMO

Sled tests focused on pelvis behavior and submarining can be found in the literature. However, they were performed either with rigid seats or with commercial seats. The objective of this study was to get reference tests to assess the submarining ability of dummies in more realistic conditions than on rigid seat, but still in a repeatable and reproducible setup. For this purpose, a semi-rigid seat was developed, which mimics the behavior of real seats, although it is made of rigid plates and springs that are easy to reproduce and simulate with an FE model. In total, eight PMHS sled tests were performed on this semirigid seat to get data in two different configurations: first in a front seat configuration that was designed to prevent submarining, then in a rear seat configuration with adjusted spring stiffness to generate submarining. All subjects sustained extensive rib fractures from the shoulder belt loading. No pelvis fractures and no submarining were observed in the front seat configuration, but two subjects sustained lumbar vertebrae fractures. In the rear seat configuration, all subjects sustained pelvic fractures and demonstrated submarining. Corridors were constructed for the external forces and the PMHS kinematics. They are provided in this paper as new reference tests to assess the biofidelity of human surrogates in different configurations that either result in submarining or do not. In future, it is intended to analyze further seat and restraint system configurations to be able to define a submarining predictor.


Assuntos
Acidentes de Trânsito , Cadáver , Vértebras Lombares/lesões , Pelve/fisiologia , Cintos de Segurança , Fraturas da Coluna Vertebral , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos
13.
Nano Lett ; 15(12): 7970-5, 2015 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-26523952

RESUMO

Filamentary-based oxide resistive memory is considered as a disruptive technology for nonvolatile data storage and reconfigurable logic. Currently accepted models explain the resistive switching in these devices through the presence/absence of a conductive filament (CF) that is described as a reversible nanosized valence-change in an oxide material. During device operation, the CF cycles billion of times at subnanosecond speed, using few tens of microamperes as operating current and thus determines the whole device's performance. Despite its importance, the CF observation is hampered by the small filament size and its minimal compositional difference with the surrounding material. Here we show an experimental solution to this problem and provide the three-dimensional (3D) characterization of the CF in a scaled device. For this purpose we have recently developed a tomography technique which combines the high spatial resolution of scanning probe microscopy with subnanometer precision in material removal, leading to a true 3D-probing metrology concept. We locate and characterize in three-dimensions the nanometric volume of the conductive filament in state-of-the-art bipolar oxide-based devices. Our measurements demonstrate that the switching occurs through the formation of a single conductive filament. The filaments exhibit sizes below 10 nm and present a constriction near the oxygen-inert electrode. Finally, different atomic-size contacts are observed as a function of the programming current, providing evidence for the filament's nature as a defects modulated quantum contact.

14.
Front Behav Neurosci ; 8: 390, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25477793

RESUMO

Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 - two genes implicated in autism-like deficits - was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods.

15.
Nano Lett ; 14(5): 2401-6, 2014 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-24720425

RESUMO

The basic unit of information in filamentary-based resistive switching memories is physically stored in a conductive filament. Therefore, the overall performance of the device is indissolubly related to the properties of such filament. In this Letter, we report for the first time on the three-dimensional (3D) observation of the shape of the conductive filament. The observation of the filament is done in a nanoscale conductive-bridging device, which is programmed under real operative conditions. To obtain the 3D-information we developed a dedicated tomography technique based on conductive atomic force microscopy. The shape and size of the conductive filament are obtained in three-dimensions with nanometric resolution. The observed filament presents a conical shape with the narrow part close to the inert-electrode. On the basis of this shape, we conclude that the dynamic filament-growth is limited by the cation transport. In addition, we demonstrate the role of the programming current, which clearly influences the physical-volume of the induced conductive filaments.

16.
ACS Appl Mater Interfaces ; 5(19): 9605-14, 2013 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-23992550

RESUMO

A low-temperature (225-300 °C) solid-vapor reaction process is reported for the synthesis of ultrathin NiGe films (∼6-23 nm) on 300 mm Si wafers covered with thermal oxide. The films were prepared via catalytic chemical vapor reaction of germane (GeH4) gas with physical vapor deposited (PVD) Ni films of different thickness (2-10 nm). The process optimization by investigating GeH4 partial pressure, reaction temperature, and time shows that low resistive, stoichiometric, and phase pure NiGe films can be formed within a broad window. NiGe films crystallized in an orthorhombic structure and were found to exhibit a smooth morphology with homogeneous composition as evidenced by glancing angle X-ray diffraction (GIXRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and Rutherford back-scattering (RBS) analysis. Transmission electron microscopy (TEM) analysis shows that the NiGe layers exhibit a good adhesion without voids and a sharp interface on the thermal oxide. The NiGe films were found to be morphologically and structurally stable up to 500 °C and exhibit a resistivity value of 29 µΩ cm for 10 nm NiGe films.

17.
Resuscitation ; 84(3): 343-50, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23146879

RESUMO

BACKGROUND: The independent prognostic significance of postanoxic status epilepticus (PSE) has not been evaluated prospectively since the introduction of therapeutic hypothermia. We studied 1-year functional outcomes and their determinants in comatose survivors of cardiac arrest (CA), with special attention to PSE. METHODS: 106 comatose CA survivors admitted to the intensive care unit in 2005-2010 were included in a prospective observational study. The main outcome measure was a Cerebral Performance Category scale (CPC) of 1 or 2 (favorable outcome) 1 year after CA. RESULTS: CA occurred out-of-hospital in 89 (84%) patients and was witnessed from onset in 94 (89%). Median times were 6 min (IQR, 0-11) from CA to first-responder arrival and 23 min (14-40) from collapse to return of spontaneous circulation. PSE was diagnosed in 33 (31%) patients at a median of 39 h (4-49) after CA. PSE was refractory in 24 (22%) cases and malignant in 19 (20%). After 1 year, 31 (29.3%) patients had favorable outcomes including 2 (6.44%) with PSE. Factors independently associated with poor outcome (CPC ≥ 3) were PSE (odds ratio [OR], 14.28; 95% confidence interval [95% CI], 2.77-50.0; P=0.001), time to restoration of spontaneous circulation (OR, 1.04/min; 95% CI, 1-1.07; P=0.035), and LOD score on day 1 (OR, 1.28/point; 95% CI, 1.08-1.54; P=0.003). CONCLUSION: PSE strongly and independently predicts a poor outcome in comatose CA survivors receiving therapeutic hypothermia, but some patients with PSE survive with good functional outcomes. PSE alone is not sufficient to predict failure to awaken after CA in the era of therapeutic hypothermia.


Assuntos
Coma/complicações , Hipotermia Induzida/métodos , Parada Cardíaca Extra-Hospitalar/complicações , Estado Epiléptico/epidemiologia , Idoso , Coma/diagnóstico , Coma/fisiopatologia , Eletroencefalografia , Feminino , Seguimentos , França/epidemiologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Estado Epiléptico/etiologia , Estado Epiléptico/fisiopatologia , Taxa de Sobrevida/tendências , Fatores de Tempo
18.
World J Urol ; 30(3): 419-26, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21892656

RESUMO

OBJECTIVE: This study's aim was to describe and evaluate outcomes of medical strategies used for lower urinary tract symptoms (LUTS) treatment in general practice and to assess impact of LUTS on patients' general health-related quality of life (HRQoL). METHODS: This cross-sectional observational study was conducted by French general practitioners. Eligible patients were males aged ≥50 years, diagnosed for at least one year and currently treated for LUTS due to benign prostatic hyperplasia (BPH). Several validated questionnaires were documented by patients to assess severity of LUTS (IPSS), specific quality of life (IPSS-Q8), impact of LUTS (BII), LUTS evolution (VNS) and general HRQoL (EQ-5D). RESULTS: Among 1,098 patients included, 82.7% were treated with monotherapies and 17.3% with combinations. Mean treatment duration was 5.2 ± 3.2 years, and 47.2% of patients had at least one treatment modification since initiation. Patients reported diminished quality of life (IPSS-Q8 ≥3) (42.3%), persisting symptoms (IPSS-score ≥12) (35.5%), symptoms worsening (VNS-score ≤-1) (18.8%) and high bother (BII-score ≥9) (2.6%). Globally, 52.8% had at least one of these unsatisfactory outcomes. Regarding general HRQoL, mean EQ-5D utility significantly decreased with LUTS severity (mild: 0.90 ± 0.12; moderate: 0.81 ± 0.21; and severe symptoms: 0.73 ± 0.25; P < 0.001). As well, all five-dimensions of EQ-5D were significantly altered in patients with moderate-to-severe LUTS (<0.001), especially 'Pain/Discomfort' and 'Anxiety/Depression'. In multivariate analyses including age and comorbidities, EQ-5D utility index remained negatively associated with each additional unit in the IPSS-score. CONCLUSIONS: This study shows that around half of BPH patients medically treated report unsatisfactory outcomes, suggesting consequential unmet medical needs in general practice. Also, moderate-to-severe LUTS significantly impact on general HRQoL.


Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Antagonistas Adrenérgicos alfa/uso terapêutico , Medicina Geral , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Fitoterapia , Hiperplasia Prostática/complicações , Qualidade de Vida/psicologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Quimioterapia Combinada , França , Clínicos Gerais , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento
19.
Nanotechnology ; 22(8): 085302, 2011 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-21242623

RESUMO

Carbon nanotubes (CNT) are known to be materials with potential for manufacturing sub-20 nm high aspect ratio vertical interconnects in future microchips. In order to be successful with respect to contending against established tungsten or copper based interconnects, though, CNT must fulfil their promise of also providing low electrical resistance in integrated structures using scalable integration processes fully compatible with silicon technology. Hence, carefully engineered growth and integration solutions are required before we can fully exploit their potentialities. This work tackles the problem of optimizing a CNT integration process from the electrical perspective. The technique of measuring the CNT resistance as a function of the CNT length is here extended to CNT integrated in vertical contacts. This allows extracting the linear resistivity and the contact resistance of the CNT, two parameters to our knowledge never reported separately for vertical CNT contacts and which are of utmost importance, as they respectively measure the quality of the CNT and that of their metal contacts. The technique proposed allows electrically distinguishing the impact of each processing step individually on the CNT resistivity and the CNT contact resistance. Hence it constitutes a powerful technique for optimizing the process and developing CNT contacts of superior quality. This can be of relevant technological importance not only for interconnects but also for all those applications that rely on the electrical properties of CNT grown with a catalytic chemical vapor deposition method at low temperature.

20.
BJU Int ; 105(1): 49-56, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20132102

RESUMO

OBJECTIVE: To calculate the total cost per patient of prostate cancer treatment and the economic cost burden by stage, in the first year after diagnosis, for five European countries. METHODS: Data from the Information Management Systems, Inc. database, survival data, expert opinion, published data and unit costs from various published official sources were used to calculate total costs per patient by stage for each country, from a payer's perspective. Diagnostic costs, first surgery, radio-, chemo- and hormonal therapy costs were included. Costs were aggregated for incident cases. RESULTS: The mean direct costs per patient for initial treatment were euro3698 in Germany, euro3256 in Spain, euro3682 in the UK, euro5226 in Italy and euro5851 in France. The total costs for all diagnosed patients in the first year from diagnosis were (million euro) 116.7 (UK), 244 (Germany), 385 (France), 202 (Italy) and 114.6 (Spain). CONCLUSIONS: The direct initial healthcare cost burden of the most common non-skin-related male cancer, prostate cancer, in France, Germany, Italy, Spain and the UK is considerable. Given the high and increasing prevalence of prostate cancer due to ageing populations in Europe, and the significant cost burden of the disease, national health policy makers should be aware of prostate cancer as a priority disease area.


Assuntos
Neoplasias da Próstata/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Métodos Epidemiológicos , Europa (Continente)/epidemiologia , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia
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