3D ICEPIC simulations of pulsed relativistic magnetron with transparent cathode : a comparative study with 3D MAGIC simulations

Ongoing research at the University of New Mexico (UNM) shows significant improvement in the start time and rate of build-up of microwave oscillations in a relativistic magnetron that uses a transparent cathode. In recent studies conducted at UNM the experimental results and the results of numerical simulations using the 3-dimensional particle-in-cell (PIC) code MAGIC have shown strong correlation. For this research a 3-dimensional PIC code ICEPIC developed at the Air Force Research Laboratory (AFRL) was used to simulate the A6 magnetron geometry with a transparent cathode. The results were compared with the work done at UNM to test the fidelity of the two simulation codes. Output parameters such as microwave power, microwave frequency, anode current, and leakage current with respect to the axial magnetic field were compared. ICEPIC simulations were run on a parallel architecture with 64 CPUs at a grid resolution of 1mmx 1mmy 1mmz in the 3-dimensional Cartesian coordinate system. These simulations consisted of roughly 6 million active grid cells and 16 million particles. Results indicated agreement between results from ICEPIC and MAGIC to within 20% for standard performance parameters. ICEPIC simulations also confirmed oscillation of the A6 magnetron with transparent cathode at 4 GHz in the 2\u03c0-mode

Measuring the health-related Sustainable Development Goals in 188 countries : a baseline analysis from the Global Burden of Disease Study 2015

Background In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). Methods We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. Findings In 2015, the median health-related SDG index was 59.3 (95% uncertainty interval 56.8-61.8) and varied widely by country, ranging from 85.5 (84.2-86.5) in Iceland to 20.4 (15.4-24.9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r(2) = 0.88) and the MDG index (r(2) = 0.2), whereas the non-MDG index had a weaker relation with SDI (r(2) = 0.79). Between 2000 and 2015, the health-related SDG index improved by a median of 7.9 (IQR 5.0-10.4), and gains on the MDG index (a median change of 10.0 [6.7-13.1]) exceeded that of the non-MDG index (a median change of 5.5 [2.1-8.9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened. Interpretation GBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to effectively address the expanded scope of the health-related SDGs.Peer reviewe

Physiological mechanisms of dyspnea during exercise in the presence of external thoracic restriction: role of increased neural respiratory motor drive

Background & rationale. "Dyspnea" refers to the awareness of breathing discomfort that accompanies an increase in physical activity in health and across various diseases. It is arguably the most severe and burdensome symptom experienced by patients with chronic pulmonary disorders and is an important contributor to physical activity-limitation and adverse health outcomes, including hospitalization and death. Nevertheless, the mechanisms of dyspnea on exertion in health and disease remain partially understood. Accumulating evidence implicates neuromechanical uncoupling of the respiratory system as a likely mechanism of activity-related dyspnea, particularly in patients with chronic pulmonary diseases. According to this hypothesis, sensory intensity and unpleasantness ratings of dyspnea increase as a function of the widening disparity (as exercise progresses) between neural respiratory drive and the simultaneous response of the respiratory system, particularly as it relates to tidal volume (VT) expansion. An alternative and largely untested hypothesis states that the increased perception of dyspnea during exercise may reflect the awareness of increased neural respiratory drive needed achieve any given ventilation (V· E) in the presence of "abnormal" restrictive constraints on VT expansion. To date, the contribution of pathophysiological abnormalities in neural respiratory drive, dynamic respiratory mechanics and their interaction to the symptom of dyspnea during exercise in patients with chronic pulmonary disorders has proved difficult to study (beyond correlation) due to the presence of multiple co-morbidities that may independently contribute to the perception of dyspnea. Research Objectives. In light of the information cited above, the objectives of this research project were to better understand the physiological mechanisms of exertional dyspnea. Methods. This randomized cross-over study examined the acute effects of external thoracic restriction by chest wall strapping (CWS) – an accepted model of the "abnormal" restrictive constraints on VT expansion typical of patients with chronic pulmonary disorders - on detailed assessments of V· E, breathing pattern, dynamic respiratory mechanics, neural respiratory drive (as assessed by changes in the diaphragm electromyogram; EMGdi), and sensory intensity and unpleasantness ratings of dyspnea during symptom-limited incremental cycle exercise testing in 20 healthy, young men with normal lung function and cardiorespiratory fitness. Results. The key findings of this study include: [1] relatively greater dynamic mechanical constraints on VT expansion were evident during exercise with vs. without CWS; [2] EMGdi was consistently higher during exercise with vs. without CWS; [3] CWS had no effect on neuromechanical coupling of the respiratory system, as evidenced by relative preservation of the relationship between increasing EMGdi and VT expansion (adjusted for CWS-induced reductions in vital capacity) during exercise; [4] sensory intensity and unpleasantness ratings of dyspnea were significantly higher during exercise with vs. without CWS; and [5] CWS had no effect on the relationship between increasing EMGdi and each of the intensity and unpleasantness of dyspnea during progressive exercise. Conclusions & implications. We concluded that the increased perception of dyspnea during exercise with CWS could not be readily explained by increased neuromechanical uncoupling of the respiratory system, but that it likely reflected the awareness of increased neural respiratory drive needed to overcome the "abnormal" restrictive constraints on VT expansion. These findings may have implications for our understanding of the pathophysiological mechanisms of exertional dyspnea causation in patients with chronic restrictive lung disorders. This information, in turn, may aid in the development of more effective dyspnea relieving interventions for use in these patients.Contexte et raisonnement. La «dyspnée» désigne une prise de conscience de gêne respiratoire se manifestant généralement à l'effort autant chez ceux en santé que ceux atteints de diverses maladies. Sans doute, il est symptôme le plus lourdement ressenti par patients atteints de maladies pulmonaires chroniques (MPC) pour son effet limitant sur l'activité physique et effet nocif sur la santé, y compris l'hospitalisation et la mort. Néanmoins, les mécanismes de la dyspnée d'effort en temps de santé et maladie restent que partiellement comprises. Des étudies ultérieurs suggèrent le découplage neuromécanique du système respiratoire comme mécanisme de dyspnée d'effort, en particulier chez patients atteints de MPC. Selon cette hypothèse, l'intensité sensorielle et le sentiment de malaise augmentent en fonction d'une disparité croissante entre pulsion respiratoire neuronale et réaction simultanée du système respiratoire, concernant notamment le volume courant (VT) d'extension. Une hypothèse alternative et largement non vérifiée suggère qu'une perception de la dyspnée élevée durant exercice reflète une prise de conscience d'une pulsion respiratoire neuronale nécessaire pour atteindre une ventilation (V· E) donnée lors de contraintes "anormales" sur l'expansion VT. À ce jour, la contribution des anomalies physiopathologiques sur la pulsion respiratoire neural, mécanique respiratoire dynamique et symptôme de la dyspnée au cours de l'exercice chez patients atteints de MPC s'est révélée difficile à étudier (au-delà de corrélation) en raison de présence de multiples comorbidités contribuant indépendamment à la perception de la dyspnée. Objectif. En guise de l'information présentée précédemment, nous tentons de mieux comprendre les mécanismes physiologiques de dyspnée d'effort. Méthode. Cette étude randomisée, contrôlée et croisée a permis d'examiner les effets aigus de la restriction thoracique externe par le cerclage de paroi thoracique (chest wall strapping, CWS),- un modèle accepté qui assimile les contraintes restrictives "anormales" sur l'expansion du VT de patients avec troubles pulmonaires chroniques - sur la V· E, mode de respiration, mécanique respiratoire dynamique, pulsion respiratoire neural (évaluée par changements dans l'électromyogramme du diaphragme; EMGdi), cotes d'intensité sensorielle et malaise accompagnant la dyspnée au cours d'épreuve incrémental d'effort limitée par symptômes, dans 20 jeunes hommes en santé et à fonctions pulmonaire et cardiorespiratoire normaux. Résultats. Les résultats principaux furent : [1] Les contraintes mécaniques dynamiques sur l'expansion du VT étaient relativement plus grandes durant effort avec CWS que sans; [2] L'EMGdi était systématiquement plus élevé lors de l'effort avec CWS que sans; [3] Le CWS n'avait aucun effet sur le découplage neuromécanique du système respiratoire, comme la relation entre EMGdi et expansion du VT (normalisée selon la réduction de la capacité vitale causée par le CWS) durant effort a été maintenue. [4] L'intensité sensorielle et le sentiment de malaise accompagnant la dyspnée étaient sensiblement plus élevés durant effort avec CWS que sans; et [5] Le CWS n'a eut aucun effet sur la relation entre une l'EMGdi augmentée, et l'intensité sensorielle et malaise ressentie, pris séparément durant l'effort progressif. Conclusions. Nous concluons que la perception accrue de la dyspnée durant effort avec CWS n'est pas aisément expliquée par découplage neuromécanique du système respiratoire élevé, mais qu'elle reflète plutôt la prise de conscience de la pulsion respiratoire neural supplémentaire nécessaire pour surmonter les contraintes restrictives « anormales » sur l'expansion du VT. Nos résultants permettent d'approfondir notre compréhension des mécanismes physiopathologiques causant la dyspnée d'effort chez patients à troubles pulmonaires chroniques, et s'avère important pour le développement de modalités soulageant la dyspnée chez ces patients dans le futur

25-Hydroxycholesterol exerts both a cox-2-dependent transient proliferative effect and cox-2-independent cytotoxic effect on bovine endothelial cells in a time- and cell-type-dependent manner

Abstract Background 25-hydroxycholesterol (25-OHC) is a product of oxidation of dietary cholesterol present in human plasma. 25-OHC and other oxidized forms of cholesterol are implicated in modulating inflammatory responses involved in development of atherosclerosis and colon carcinogenesis. Methods Primary lymphatic, venous and arterial endothelial cells isolated from bovine mesentery (bmLEC, bmVEC, bmAEC) were treated with 25-OHC and tested for several different cellular parameters. Results We found 25-OHC to be a potent inducer of cyclooxygenase-2 (Cox-2, prostaglandin G-H synthase-2) expression in bovine mesenteric lymphatic, venous, and arterial endothelial cells. The induction of Cox-2 expression in endothelial cells by 25-OHC led to an initial increase in cellular proliferation that was inhibited by the Cox-2 selective inhibitor celecoxib (Celebrex). Prolonged exposure to 25-OHC was cytotoxic. Furthermore, endothelial cells induced to express Cox-2 by 25-OHC were more sensitive to the effects of the Cox-2 selective inhibitor celecoxib (Celebrex). These results suggest that some effects of 25-OHC on cells may be dependent on Cox-2 enzymatic activity. Conclusions Cox-2 dependent elevating effects of 25-OHC on endothelial cell proliferation was transient. Prolonged exposure to 25-OHC caused cell death and enhanced celecoxib-induced cell death in a cell-type dependent manner. The lack of uniform response by the three endothelial cell types examined suggests that our model system of primary cultures of bmLECs, bmVECs, and bmAECs may aid the evaluation of celecoxib in inhibiting proliferation of different types of tumour-associated endothelial cells

Physiological and Perceptual Responses to Incremental Exercise Testing in Healthy Men: Effect of Exercise Test Modality

In a randomized cross-over study of 15 healthy men aged 20-30 years, we compared physiological and perceptual responses during treadmill and cycle exercise test protocols matched for increments in work rate – the source of increased locomotor muscle metabolic and contractile demands. The rates of O2 consumption (V̇O2) and CO2 production (V̇CO2) were higher at the peak of treadmill vs. cycle testing (p≤0.05). Nevertheless, work rate, minute ventilation (V̇E), tidal volume (VT), breathing frequency (fR), inspiratory capacity (IC), inspiratory reserve volume (IRV), tidal esophageal (Pes,tidal) and transdiaphragmatic pressure swings (Pdi,tidal), peak expiratory gastric pressures (Pga,peak), the root mean square of the diaphragm EMG (EMGdi,rms) expressed as a percentage of maximum EMGdi,rms (EMGdi,rms%max), and dyspnea ratings were similar at the peak of treadmill vs. cycle testing (p>0.05). Ratings of leg discomfort were higher at the peak of cycle vs. treadmill exercise (p≤0.05), even though peak V̇O2 was lower during cycling. V̇O2, V̇CO2, V̇E, fR, Pes,tidal, Pdi,tidal and Pga,peak were higher (p≤0.05), while VT, IC, IRV, EMGdi,rms%max, and ratings of dyspnea and leg discomfort were similar (p>0.05) at all or most submaximal work rates during treadmill vs. cycle exercise. Our findings highlight important differences (and similarities) in physiological and perceptual responses at maximal and submaximal work rates during incremental treadmill and cycle exercise testing protocols. The lack of effect of exercise test modality on peak work rate advocates for the use of this readily available parameter to optimize training intensity determination, regardless of exercise training mode.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

The Role of Serotonin during Skin Healing in Post-Thermal Injury

Post-burn trauma significantly raises tissue serotonin concentration at the initial stages of injury, which leads us to investigate its possible role in post burn wound healing. Therefore, we planned this study to examine the role of serotonin in wound healing through in vitro and in vivo models of burn injuries. Results from in vitro analysis revealed that serotonin decreased apoptosis and increased cell survival significantly in human fibroblasts and neonatal keratinocytes. Cellular proliferation also increased significantly in both cell types. Moreover, serotonin stimulation significantly accelerated the cell migration, resulting in narrowing of the scratch zone in human neonatal keratinocytes and fibroblasts cultures. Whereas, fluoxetine (a selective serotonin reuptake inhibitor) and ketanserin (serotonin receptor 2A inhibitor) reversed these effects. Scald burn mice model (20% total body surface area) showed that endogenous serotonin improved wound healing process in control group, whereas fluoxetine and ketanserin treatments (disruptors of endogenous serotonin stimulation), resulted in poor reepithelization, bigger wound size and high alpha smooth muscle actin (α-SMA) count. All of these signs refer a prolonged differentiation state, which ultimately exhibits poor wound healing outcomes. Collectively, data showed that the endogenous serotonin pathway contributes to regulating the skin wound healing process. Hence, the results of this study signify the importance of serotonin as a potential therapeutic candidate for enhancing skin healing in burn patients