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1.
Nature ; 601(7894): 542-548, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35082418

RESUMEN

Obtaining a burning plasma is a critical step towards self-sustaining fusion energy1. A burning plasma is one in which the fusion reactions themselves are the primary source of heating in the plasma, which is necessary to sustain and propagate the burn, enabling high energy gain. After decades of fusion research, here we achieve a burning-plasma state in the laboratory. These experiments were conducted at the US National Ignition Facility, a laser facility delivering up to 1.9 megajoules of energy in pulses with peak powers up to 500 terawatts. We use the lasers to generate X-rays in a radiation cavity to indirectly drive a fuel-containing capsule via the X-ray ablation pressure, which results in the implosion process compressing and heating the fuel via mechanical work. The burning-plasma state was created using a strategy to increase the spatial scale of the capsule2,3 through two different implosion concepts4-7. These experiments show fusion self-heating in excess of the mechanical work injected into the implosions, satisfying several burning-plasma metrics3,8. Additionally, we describe a subset of experiments that appear to have crossed the static self-heating boundary, where fusion heating surpasses the energy losses from radiation and conduction. These results provide an opportunity to study α-particle-dominated plasmas and burning-plasma physics in the laboratory.

3.
Phys Rev Lett ; 125(21): 215001, 2020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-33274978

RESUMEN

Energy flow and balance in convergent systems beyond petapascal energy densities controls the fate of late-stage stars and the potential for controlling thermonuclear inertial fusion ignition. Time-resolved x-ray self-emission imaging combined with a Bayesian inference analysis is used to describe the energy flow and the potential information stored in the rebounding spherical shock at 0.22 PPa (2.2 Gbar or billions of atmospheres pressure). This analysis, together with a simple mechanical model, describes the trajectory of the shell and the time history of the pressure at the fuel-shell interface, ablation pressure, and energy partitioning including kinetic energy of the shell and internal energy of the fuel. The techniques used here provide a fully self-consistent uncertainty analysis of integrated implosion data, a thermodynamic-path independent measurement of pressure in the petapascal range, and can be used to deduce the energy flow in a wide variety of implosion systems to petapascal energy densities.

4.
Phys Rev Lett ; 121(2): 025001, 2018 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-30085737

RESUMEN

We have developed an experimental platform for the National Ignition Facility that uses spherically converging shock waves for absolute equation-of-state (EOS) measurements along the principal Hugoniot. In this Letter, we present one indirect-drive implosion experiment with a polystyrene sample that employs radiographic compression measurements over a range of shock pressures reaching up to 60 Mbar (6 TPa). This significantly exceeds previously published results obtained on the Nova laser [R. Cauble et al., Phys. Rev. Lett. 80, 1248 (1998)PRLTAO0031-900710.1103/PhysRevLett.80.1248] at a strongly improved precision, allowing us to discriminate between different EOS models. We find excellent agreement with Kohn-Sham density-functional-theory-based molecular dynamics simulations.

5.
Child Care Health Dev ; 41(2): 222-9, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25338500

RESUMEN

BACKGROUND: This article presents findings from the development and evaluation of The KIT: Keeping It Together™â€…for Youth (the 'Youth KIT'). The Youth KIT is a resource intended to assist youth with disabilities during their teenage years and during the transition to adulthood to give information to others about themselves, get from others about themselves, and organize their own information to the best of their ability. METHODS: Thirty-six youth between the ages of 12 and 25 with physical and developmental disabilities were active participants in the development of the Youth KIT and partnered with a multidisciplinary team to conduct the qualitative evaluation. Focus groups and individual interviews were used in three phases of evaluation. RESULTS: The results of qualitative content analysis found the Youth KIT to be useful for a variety of youth in different contexts. The themes that emerged about the utility and impact of the Youth KIT were: (1) self-discovery for youth; and (2) the importance of the 'fit' between youth and mentors to support youth as they started to use the Youth KIT. CONCLUSION: Clinical implications for healthcare providers working with youth during the transition to adulthood include recognition that discussions about adult goals should be a continuous dialogue throughout adolescence rather than a 'special' conversation occurring at the time of discharge from paediatric services.


Asunto(s)
Discapacidades del Desarrollo/rehabilitación , Personas con Discapacidad/rehabilitación , Gestión de la Información/organización & administración , Transición a la Atención de Adultos/organización & administración , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Mentores , Ontario , Investigación Cualitativa , Autoimagen , Adulto Joven
6.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38958513

RESUMEN

3D asymmetries are major degradation mechanisms in inertial-confinement fusion implosions at the National Ignition Facility (NIF). These asymmetries can be diagnosed and reconstructed with the neutron imaging system (NIS) on three lines of sight around the NIF target chamber. Conventional tomographic reconstructions are used to reconstruct the 3D morphology of the implosion using NIS [Volegov et al., J. Appl. Phys. 127, 083301 (2020)], but the problem is ill-posed with only three imaging lines of sight. Asymmetries can also be diagnosed with the real-time neutron activation diagnostics (RTNAD) and the neutron time-of-flight (nToF) suite. Since the NIS, RTNAD, and nToF each sample a different part of the implosion using different physical principles, we propose that it is possible to overcome the limitations of too few imaging lines of sight by performing 3D reconstructions that combine information from all three heterogeneous data sources. This work presents a new machine learning-based reconstruction technique to do just this. By using a simple physics model and group of neural networks to map 3D morphologies to data, this technique can easily account for data of multiple different types. A simple proof-of-principle is presented, demonstrating that this technique can accurately reconstruct a hot-spot shape using synthetic primary neutron images and a hot-spot velocity vector. In particular, the hot-spot's asymmetry, quantified as spherical harmonic coefficients, is reconstructed to within ±4% of the radius in 90% of test cases. In the future, this technique will be applied to actual NIS, RTNAD, and nToF data to better understand 3D asymmetries at the NIF.

7.
Nat Commun ; 15(1): 2975, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38582938

RESUMEN

Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1. Analysis shows that including these three corrections alone accounts for the measured fusion performance variability in the two highest performing experimental campaigns on the NIF to within error. Here we quantify the performance sensitivity to mode-2 symmetry in the burning plasma regime and apply the results, in the form of an empirical correction to a 1D performance model. Furthermore, we find the sensitivity to mode-2 determined through a series of integrated 2D radiation hydrodynamic simulations to be consistent with the experimentally determined sensitivity only when including alpha-heating.

8.
Phys Rev E ; 107(1-2): 015202, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36797905

RESUMEN

In order to understand how close current layered implosions in indirect-drive inertial confinement fusion are to ignition, it is necessary to measure the level of alpha heating present. To this end, pairs of experiments were performed that consisted of a low-yield tritium-hydrogen-deuterium (THD) layered implosion and a high-yield deuterium-tritium (DT) layered implosion to validate experimentally current simulation-based methods of determining yield amplification. The THD capsules were designed to reduce simultaneously DT neutron yield (alpha heating) and maintain hydrodynamic similarity with the higher yield DT capsules. The ratio of the yields measured in these experiments then allowed the alpha heating level of the DT layered implosions to be determined. The level of alpha heating inferred is consistent with fits to simulations expressed in terms of experimentally measurable quantities and enables us to infer the level of alpha heating in recent high-performing implosions.

9.
J Exp Med ; 140(3): 837-52, 1974 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-4370241

RESUMEN

Experiments have been designed to test the hypothesis that soluble mediator production and T-cell-mediated cytotoxicity are necessarily related phenomena, and that soluble mediators may be involved in the mechanism of cytolysis. To this end, agents known to inhibit T-cell-mediated lysis in vitro have been studied for their effects on the production of two lymphocyte-derived mediators, lymphotoxin (LT) and migration inhibitory factor (MIF). A clear dissociation between mediator production and cell-mediated cytolysis was found using inhibitors of protein synthesis. Pactamycin and emetine, in doses of 10(-7) M to 10(-6) M, suppressed production of MIF and LT with only slight effect on killing of mastocytoma cells by immune T cells. On the other hand colchicine and vinblastine inhibited T-cell-mediated cytolysis in a dose-related manner but had no significant effect on either MIF or LT production, A striking dichotomy was also observed after augmentation of intracellular cyclic 3'5' adenosine monophosphate (cAMP) levels with cholera enterotoxin. Increased cAMP levels were associated with abrogation of direct lytic activity, but were without significant effect on MIF or LT production in guinea pigs or mice. These findings indicate that mediator production and direct lymphocyte-mediated cytolysis can be experimentally dissociated and represent independent cell-mediated immune functions.


Asunto(s)
Inmunidad Celular , Linfotoxina-alfa , Factores Inhibidores de la Migración de Macrófagos , Linfocitos T/inmunología , Animales , Antibióticos Antineoplásicos/farmacología , Radioisótopos de Cromo , AMP Cíclico/metabolismo , Pruebas Inmunológicas de Citotoxicidad , Depresión Química , Emetina/farmacología , Enterotoxinas , Cobayas , Leucina/metabolismo , Sarcoma de Mastocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Bazo/citología , Bazo/inmunología , Linfocitos T/metabolismo , Tritio , Tuberculina , Vibrio cholerae/inmunología
10.
Phys Rev E ; 102(5-1): 053210, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33327091

RESUMEN

High-energy-density (HED) experiments in convergent geometry are able to test physical models at pressures beyond hundreds of millions of atmospheres. The measurements from these experiments are generally highly integrated and require unique analysis techniques to procure quantitative information. This work describes a methodology to constrain the physics in convergent HED experiments by adapting the methods common to many other fields of physics. As an example, a mechanical model of an imploding shell is constrained by data from a thin-shelled direct-drive exploding-pusher experiment on the OMEGA laser system using Bayesian inference, resulting in the reconstruction of the shell dynamics and energy transfer during the implosion. The model is tested by analyzing synthetic data from a one-dimensional hydrodynamics code and is sampled using a Markov chain Monte Carlo to generate the posterior distributions of the model parameters. The goal of this work is to demonstrate a general methodology that can be used to draw conclusions from a wide variety of HED experiments.

11.
J Asian Nat Prod Res ; 11(2): 159-67, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19219729

RESUMEN

We investigated the potential of symplocomoside (1) and symponoside (2), glycosides isolated from the bark of Symplocos racemosa to inhibit thymidine phosphorylase (TP) activity and associated angiogenesis. Compound 1 was a reversible, noncompetitive inhibitor of deoxythymidine binding to TP (IC(50) = 65.45 +/- 5.08 microM; K(i) = 62.83 +/- 2.10 microM) and 2 was a reversible, uncompetitive inhibitor (IC(50) = 94.17 +/- 4.05 microM; K(i) = 101.95 +/- 1.65 microM). Molecular modeling analysis indicated that both compounds bound at the active site of the enzyme but not solely to amino acid residues involved in catalysis. Both compounds were active in in vitro angiogenic assays inhibiting endothelial cell migration and invasion in Matrigel, but did not inhibit growth factor-induced proliferation and were not cytotoxic. Compound 1 may have potential as an anti-angiogenic and anti-tumor agent.


Asunto(s)
Inhibidores de la Angiogénesis/aislamiento & purificación , Inhibidores de la Angiogénesis/farmacología , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Modelos Moleculares , Timidina Fosforilasa/antagonistas & inhibidores , Inhibidores de la Angiogénesis/química , Bencimidazoles , Ciclopentanos , Ensayos de Selección de Medicamentos Antitumorales , Glicósidos/química , Humanos , Cinética , Conformación Molecular , Estructura Molecular , Corteza de la Planta/química
12.
Biotechniques ; 66(2): 79-84, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30370778

RESUMEN

Geometry of the placental villous vasculature is a key determinant of maternal-fetal nutrient exchange for optimal fetal growth. Recent advances in tissue clarification techniques allow for deep high-resolution imaging with confocal microscopy; however, the methodology lacks a signal:noise ratio of sufficient magnitude to allow for quantitative analysis. Thus, we sought to develop a reproducible method to investigate the 3D vasculature of the nonhuman primate placenta for subsequent data analysis. Fresh placental tissue was dissected, formalin fixed, clarified using a modified Visikol® protocol and immunolabeled for CD31 (fetal endothelium) and cytokeratin-7 (villous trophoblast) for confocal imaging of the microanatomy. We present a detailed clarification and staining protocol augmented for imaging of nonhuman primate placental tissue. The image stacks generated by this refined staining method and our data acquisition parameters can be analyzed quantitatively to provide insights regarding the villous and vascular micro-anatomy of the placenta.


Asunto(s)
Vellosidades Coriónicas/diagnóstico por imagen , Imagenología Tridimensional/métodos , Microscopía Confocal/métodos , Placenta/diagnóstico por imagen , Animales , Vellosidades Coriónicas/anatomía & histología , Femenino , Desarrollo Fetal/fisiología , Humanos , Placenta/anatomía & histología , Embarazo , Primates/anatomía & histología
13.
Angiogenesis ; 11(3): 245-56, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18330714

RESUMEN

Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is of physiological and pathological importance. We have investigated the anti-angiogenic potential of two naturally occurring sesterterpenes, leucosesterterpenone (compound 1) and leucosterlactone (compound 2) isolated from the Himalayan plant Leucosceptrum canum and identified as having biological activity in preliminary screening. Compound 1 inhibited fibroblast growth factor-2-induced proliferation, migration in a wounding assay, chemotaxis and tube formation with small vessel (human dermal) and large vessel (bovine aortic) endothelial cells while compound 2 was largely inactive. Both compounds were also active in an in vivo angiogenic model using the chick chorioallantoic membrane. Neither compounds showed inhibitory activity in the absence of fibroblast growth factor-2. We were able to demonstrate in a binding assay that compounds 1 and 2 bound to the fibroblast growth factor-2 receptor-1 with IC(50) values of 1.4 +/- 0.956 and 132.47 +/- 7.90 muM, respectively, with a concomitant down regulation of phosphorylated ERK1/2 but did not bind to receptor-2. Compound 1 was less hydrophobic than compound 2 and this may contribute to its increased activity. Compound 1 is a new addition to the small number of inhibitors of fibroblast growth factor-2-induced angiogenesis. The compound was a specific inhibitor in that it had no effect on vascular endothelial growth factor or epithelial growth factor-induced angiogenesis. Since angiogenesis is essential for tumour development we conclude that these compounds may have potential as anti-tumour agents.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Factor 2 de Crecimiento de Fibroblastos/antagonistas & inhibidores , Factor 2 de Crecimiento de Fibroblastos/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Sesterterpenos/farmacología , Animales , Bovinos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Embrión de Pollo , Evaluación Preclínica de Medicamentos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/fisiología , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Modelos Biológicos , Unión Proteica , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Sesterterpenos/metabolismo , Cicatrización de Heridas/efectos de los fármacos
14.
Eur J Neurol ; 15(1): 29-37, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18042242

RESUMEN

Leukaemia inhibitory factor (LIF) is a glycoprotein of the interleukin-6 family, which has potent pro-inflammatory properties and is involved in regulation of neuronal differentiation. We have previously identified its upregulation in gene microarrays following acute ischaemic stroke in man. LIF expression and localization was measured in human ischaemic stroke autopsy specimens, in a rat model of middle cerebral artery occlusion (MCAO) and in human foetal neural cell cultures following oxygen-glucose deprivation (OGD) by Western blotting and immunohistochemistry. Circulating LIF was determined in the plasma of patients in the hyper-acute stroke phase using a multiplex enzyme-linked-immunosorbent serologic assay system. Patients demonstrated an increase in LIF expression in peri-infarcted regions with localization in neurons and endothelial cells of microvessels surrounding the infarcted core. The rat MCAO model showed similar upregulation in neurons with a peak increase at 90 min. Circulating serum LIF expression was significantly decreased in the hyper-acute phase of stroke. Brain-derived neurons and glia cultured in vitro demonstrated an increase in gene/protein and protein expression respectively following exposure to OGD. Increased LIF expression in peri-infarcted regions and sequestration from the peripheral circulation in acute stroke patients are characteristic of the pathobiological response to ischaemia and tissue damage.


Asunto(s)
Isquemia Encefálica/sangre , Isquemia Encefálica/fisiopatología , Encéfalo/metabolismo , Factor Inhibidor de Leucemia/sangre , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/fisiopatología , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Animales , Encéfalo/irrigación sanguínea , Encéfalo/fisiopatología , Células Cultivadas , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Células Endoteliales , Femenino , Humanos , Infarto de la Arteria Cerebral Media/sangre , Infarto de la Arteria Cerebral Media/fisiopatología , Factor Inhibidor de Leucemia/biosíntesis , Factor Inhibidor de Leucemia/genética , Masculino , Persona de Mediana Edad , Neuroglía/metabolismo , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba/fisiología
15.
Pathobiology ; 75(4): 209-25, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18580067

RESUMEN

Formation of unstable plaques frequently results in atherothrombosis, the major cause for ischaemic stroke, myocardial infarction and peripheral arterial disease. Patients who have symptomatic thrombosis in one vascular bed are at increased risk of disease in other beds. However, the development of the disease in carotid, coronary and peripheral arteries may have different pathophysiology suggesting that more complex treatment protocols may have to be designed to reduce plaque development at different locations. In this review we describe the known risk factors, compare the developmental features of coronary and carotid plaque development and determine their association with end-point ischaemic events. Differences are also seen in the genetic contribution to plaque development as well as in the deregulation of gene and protein expression and cellular signal transduction activity of active cells in regions susceptible to thrombosis. Differences between carotid and coronary artery plaque development might help to explain the differences in anatomopathological appearance and risk of rupture.


Asunto(s)
Enfermedades de las Arterias Carótidas/patología , Enfermedad de la Arteria Coronaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/genética , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rotura Espontánea , Túnica Íntima/patología
16.
Cochrane Database Syst Rev ; (4): CD004823, 2006 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-17054216

RESUMEN

BACKGROUND: Cough is a very common symptom presenting to medical practitioners. Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. However cough and GORD are common ailments and their co-existence by chance is high. Also cough can induce reflux episodes. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H(2) antagonist and proton pump inhibitors (PPI)) and fundoplication. OBJECTIVES: To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease i.e. non-specific chronic cough. SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register Collaboration and Cochrane Airways Group, MEDLINE and EMBASE databases, review articles and reference lists of relevant articles were searched. The date of last search was 7th April 2006. SELECTION CRITERIA: All randomised controlled trials on GORD treatment for cough in children and adults without primary lung disease. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Two independent reviewers selected, extracted and assessed data for inclusion. Authors were contacted for further information. Data was analysed as "intention to treat" as well as "treatment received". Paediatric and adults data were considered separately. Sensitivity analyses were performed. MAIN RESULTS: Thirteen studies (3 paediatric, 10 adults) were included. Data from six were available for analysis. None of the paediatric studies could be included in meta-analysis. In adults, analysis on use of H(2) antagonist, motility agents and conservative treatment for GORD were not possible (from lack of data) and there were no controlled studies on fundoplication as an intervention. Six adult studies comparing PPI (2-3 months) to placebo were analysed for various outcomes in the meta-analysis. Enrolment of subjects for two studies were primarily from medical clinics and another 4 studies were otolaryngology clinic patients or patients with laryngitis. Using "intention to treat", pooled data from 4 studies resulted in no significant difference between treatment and placebo in total resolution of cough, Odds Ratio 0.46 (95% CI 0.19 to 1.15). Pooled data revealed no overall significant improvement in cough outcomes (end of trial or change in cough scores). Significant differences were only found in sensitivity analyses. A significant improvement in change of cough scores was found in end of intervention (2-3 months) in those receiving PPI with a standardised mean difference of -0.41 (95%CI -0.75, -0.07) using GIV analysis on cross over trials. Two studies reported improvement in cough after 5 days to 2 weeks of treatment. AUTHORS' CONCLUSIONS: There is insufficient evidence to definitely conclude that GORD treatment with PPI is universally beneficial for cough associated with GORD in adults. The beneficial effect was only seen in sub-analysis and its effect was small. The optimal duration of such a trial of therapy to evaluate response could not be ascertained in the meta-analysis although two RCTs reported significant change by 2 weeks of therapy. Clinicians should be cognisant of a period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Data in children are inconclusive. Future paediatric and adult studies are needed whereby studies should be double blind, randomised controlled, parallel design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non acid reflux whilst on therapy.


Asunto(s)
Tos/terapia , Reflujo Gastroesofágico/terapia , Adulto , Niño , Enfermedad Crónica , Tos/complicaciones , Reflujo Gastroesofágico/complicaciones , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Cochrane Database Syst Rev ; (4): CD004822, 2005 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-16235384

RESUMEN

BACKGROUND: Cough is the most common symptom which presents to doctors. Chronic cough is reported in up to 9% of preschool aged children. American general practice guidelines suggest antimicrobial treatment may be indicated in children with cough lasting > 10 days. Questions concerning the benefits and harm of antibiotic treatment for prolonged cough in children need to be resolved. OBJECTIVES: A Cochrane systematic review was undertaken to determine the efficacy of antibiotics in treating children with chronic moist cough (excluding those with bronchiectasis or other underlying respiratory illnesses). SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of relevant articles were searched. The latest searches were performed on 12th April 2004. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing antibiotics with a placebo or a control group in children with chronic moist cough were considered. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Two independent reviewers selected, extracted and assessed the data for inclusion. Authors were contacted for further information. Data were analysed as 'intention to treat'. MAIN RESULTS: Two studies were eligible for inclusion in the review. Neither study was high quality. Both studies failed to include a prospective analysis of cough quality in their inclusion criteria, although indicating >75% of children included had moist cough (Darelid 1993). A total of 140 patients, aged seven years or less, were included in meta-analysis. Treatment with antibiotics reduced the proportion of children not cured at follow-up (primary outcome measure) in both studies; pooled odds ratio (OR) was 0.13, 95% CI 0.06 to 0.32 (using intention to treat analysis), which translates to number needed to treat (NNT) of 3 (95% CI 2 to 4). No significant heterogeneity was found (fixed and random-effects model I(2) was 4%). However for this outcome measure, the overall estimate of effect and degree of statistical heterogeneity were sensitive to the model used for meta-analysis. Progression of illness, defined by requirement for further antibiotics, was significantly lower in the treatment group (OR 0.10, 95%CI 0.03 to 0.34), NNT was 4 (95% CI 3 to 5). Adverse events were not significantly increased in the treatment group. AUTHORS' CONCLUSIONS: Antibiotics are likely to be beneficial in the treatment of children with chronic moist cough. This evidence is however limited by study quality, study design and sensitivity analysis data. The use of antibiotics however has to be balanced against their well known adverse events. Further well-designed RCTs using valid cough outcome measures are needed to answer this question conclusively.


Asunto(s)
Antibacterianos/uso terapéutico , Tos/tratamiento farmacológico , Niño , Enfermedad Crónica , Tos/clasificación , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Esputo/metabolismo
18.
Cochrane Database Syst Rev ; (2): CD004823, 2005 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-15846735

RESUMEN

BACKGROUND: Cough is a very common symptom presenting to medical practitioners. Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. However cough and GORD are common ailments and their co-existence by chance is high. Also cough can induce reflux episodes. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H(2) antagonist and proton pump inhibitors (PPI)) and fundoplication. OBJECTIVES: To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease i.e. non-specific chronic cough. SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register Collaboration and Cochrane Airways Group, MEDLINE and EMBASE databases, review articles and reference lists of relevant articles were searched. The date of last search was 4th April 2004. SELECTION CRITERIA: All randomised controlled trials on GORD treatment for cough in children and adults without primary lung disease. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Two independent reviewers selected, extracted and assessed data for inclusion. Authors were contacted for further information. Data was analysed as "intention to treat" as well as "treatment received". Paediatric and adults data were considered separately. Sensitivity analyses were performed. MAIN RESULTS: 11 studies (3 paediatric, 8 adults; 383 participants) were included. None of the paediatric studies could be included in meta-analysis. In adults, analysis on use of H(2) antagonist, motility agents and conservative treatment for GORD were not possible (from lack of data) and there were no controlled studies on fundoplication as an intervention. Five adult studies comparing PPI (2-3 months) to placebo were analysed for various outcomes in the meta-analysis. Enrollment of subjects for two studies were primarily from medical clinics and another three studies were otolaryngeal clinic patients. Using "intention to treat", pooled data from three studies resulted in no significant difference between treatment and placebo in total resolution of cough. Pooled data revealed no significant improvement in cough outcomes (end of trial or change in cough scores). Significant differences were only found in sensitivity analysis. A significant improvement in change of cough scores was found in end of intervention (2-3 months) in those receiving PPI with a standardised mean difference of -0.41 (95%CI -0.75, -0.07) using GIV analysis on cross over trials. Two studies reported improvement in cough after 5 days to 2 weeks of treatment. Significant heterogeneity was found between studies using omeprazole and other PPIs. AUTHORS' CONCLUSIONS: There is insufficient evidence to definitely conclude that GORD treatment with PPI is beneficial for cough associated with GORD in adults. The beneficial effect was only seen in sub-analysis and its effect was small. The optimal duration of such a trial of therapy to evaluate response could not be ascertained in the meta-analysis although two RCTs reported significant change by two weeks of therapy. Clinicians should be cognisant of a period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Data in children are inconclusive. Future paediatric and adult studies are needed whereby studies should be double blind, randomised controlled, parallel design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non acid reflux whilst on therapy.


Asunto(s)
Tos/terapia , Reflujo Gastroesofágico/terapia , Adulto , Niño , Enfermedad Crónica , Tos/complicaciones , Reflujo Gastroesofágico/complicaciones , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
Clin Rheumatol ; 34(9): 1633-8, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25894437

RESUMEN

Magnetic resonance (MR) imaging-based disease activity scores (DAS) in axial spondyloarthritis (axSpA) are rarely employed in the normal clinical setting, whereas clinical DAS are used routinely to monitor disease activity and set thresholds for biologic treatment. The objectives of this study were to evaluate the correlation between MR and clinical DAS in a general axSpA outpatient population and to assess the difference in MR DAS in individuals with high and low clinical DAS. This was a prospective, cross-sectional observational study. Forty participants with axSpA who presented for MR of the whole spine and sacroiliac joints as part of ongoing management were included. Completion of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) was performed at the time of MR examination. MR images were scored by two independent observers using the Spondyloarthritis Research Consortium of Canada (SPARCC) MR DAS. There were weak, non-significant correlations between total SPARCC score and BASDAI (r = 0.18, p = 0.26), ASDAS using erythrocyte sedimentation rate (ASDAS-ESR) (r = 0.31, p = 0.07) and ASDAS using C-reactive protein level (ASDAS-CRP) (r = 0.31, p = 0.05). There was no significant difference in the SPARCC score of participants with high and low clinical DAS. MR DAS may provide information about disease activity not provided by the current standard of clinical DAS and may be considered as a useful adjunct in clinical practice.


Asunto(s)
Articulación Sacroiliaca/fisiopatología , Índice de Severidad de la Enfermedad , Columna Vertebral/fisiopatología , Espondilitis Anquilosante/diagnóstico , Adolescente , Adulto , Anciano , Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , Canadá , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
20.
J Comp Neurol ; 203(3): 401-24, 1981 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-6274920

RESUMEN

Cobaltous lysine applied to the distal stump of a severed optic nerve was used to study the retinal projections of normal adult goldfish. Both the termination areas of optic axons and the pathways they traveled were established. Contrary to previous descriptions of the goldfish visual system, the optic nerves do not decussate completely at the optic chiasm. Fascicles that entered the ipsilateral optic tract innervated targets in the ipsilateral thalamus and optic tectum. Other optic fibers crossed the posterior commissure from the contralateral side of the brain and also innervated the ipsilateral tectum and thalamus. In addition, optic fibers bilaterally innervated a hypothalamic target in close proximity to the infundibulum that may correspond to the nucleus tuberis lateralis. The contralateral preoptic region contained two discrete areas of innervation, each served by separate fascicles. The ipsilateral preoptic region was similarly innervated, but more sparsely. Fibers that entered the controlateral ventral thalamus originated from three fascicles and terminated in three distinct targets. In contrast, three targets in the contralateral dorsal thalamus were served by one fascicle, and fibers passed from one nucleus to the other two. Innervation of the ipsilateral thalamus was similar to that seen contralaterally. Each main optic tract divided into three tracts, two of which entered the optic tectum, while the other innervated several pretectal areas. Other fibers innervated an accessory optic nucleus located near nucleus glomerulosus. The contralateral tectum contained numerous radially oriented optic fascicles. These fascicles represented optic fibers that left thalamic and pretectal targets to enter the optic tectum from beneath the stratum periventriculare. Optic fibers were also observed in the transverse commissure, tractus rotundus, horizontal commissure, tectobulbar tract, and fasciculus retroflexus. Therefore, it appears that many of the anomalous projections seen after tectal ablation or after optic nerve crush are not in fact aberrant. Such projections probably reflect the presence of unusually large numbers of optic fibers in tracts that normally contain optic axons, as well as increased innervation of areas that normally receive sparse retinal projections. Filled tectal cells that could represent cells projecting to the retina were not observed in either tectal lobe. The ipsilateral retinal projections could not be attributed to cobaltous-lysine being transneuronally transported in readily detectable amounts.


Asunto(s)
Cobalto , Cyprinidae/fisiología , Carpa Dorada/fisiología , Lisina/análogos & derivados , Retina/fisiología , Transmisión Sináptica , Animales , Axones/fisiología , Mapeo Encefálico , Quiasma Óptico/fisiología , Área Preóptica/fisiología , Colículos Superiores/fisiología , Techo del Mesencéfalo/fisiología , Terminología como Asunto , Tálamo/fisiología
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