Low-Thrust to Solar-Sail Trajectories: A Homotopic Approach

This paper describes a novel method to compute minimum-time solar-sail trajectories starting from a given low-thrust solution. The method is based on the use homotopy and numerical continuation. Homotopy is used to link the low-thrust with the solar-sail optimal control problem. Numerical continuation is used to compute the optimal solar-sail solution, starting from a given low-thrust planar solution, which is normally easy to find. Planar solar sail trajectories are computed by means of the homotopic approach. These solutions are used to compute, in a single shooting approach, three-dimensional solar-sail trajectories, for transfer scenarios involving a small change of the orbital inclination. The proposed homotopic approach is tested against a conventional approach, based on the use of a genetic algorithm. Numerical test cases are performed both on Earth-Mars and Earth-Apophis rendezvous. The results show that the proposed method is advantageous, in terms of accuracy of the solution and computational time

Intravenous sildenafil citrate and post-cardiac surgery acute kidney injury: a double-blind, randomised, placebo-controlled trial

Clinical trial registration ISRCTN18386427. open access articleBackground This study assessed whether i.v. sildenafil citrate prevented acute kidney injury in at-risk patients undergoing cardiac surgery with cardiopulmonary bypass. Methods In a double-blind RCT, adults at increased risk of acute kidney injury undergoing cardiac surgery in a single UK tertiary centre were randomised to receive sildenafil citrate 12.5 mg kg−1 i.v. over 150 min or dextrose 5% at the commencement of surgery. The primary outcome was serum creatinine measured at six post-randomisation time points. The primary analysis used a linear mixed-effects model adjusted for the stratification variables, baseline estimated glomerular filtration rate, and surgical procedure. Secondary outcomes considered clinical events and potential disease mechanisms. Effect estimates were expressed as mean differences (MDs) or odds ratios with 95% confidence intervals. Results The analysis population comprised eligible randomised patients that underwent valve surgery or combined coronary artery bypass graft and valve surgery, with cardiopulmonary bypass, between May 2015 and June 2018. There were 60 subjects in the sildenafil group and 69 in the placebo control group. The difference between groups in creatinine concentration was not statistically significant (MD: 0.88 μmol L−1 [–5.82, 7.59]). There was a statistically significant increase in multiple organ dysfunction scores in the sildenafil group (MD: 0.54 [0.02, 1.07]; P=0.044). Secondary outcomes, and biomarkers of kidney injury, endothelial function, and inflammatory cell activation, were not significantly different between the groups. Conclusions These results do not support the use of i.v. sildenafil citrate for kidney protection in adult cardiac surgery

Exposure to Allergen Causes Changes in NTS Neural Activities after Intratracheal Capsaicin Application, in Endocannabinoid Levels and in the Glia Morphology of NTS

Allergen exposure may induce changes in the brainstem secondary neurons, with neural sensitization of the nucleus solitary tract (NTS), which in turn can be considered one of the causes of the airway hyperresponsiveness, a characteristic feature of asthma. We evaluated neurofunctional, morphological, and biochemical changes in the NTS of naive or sensitized rats. To evaluate the cell firing activity of NTS, in vivo electrophysiological experiments were performed before and after capsaicin challenge in sensitized or naive rats. Immunohistochemical studies, endocannabinoid, and palmitoylethanolamide quantification in the NTS were also performed. This study provides evidence that allergen sensitization in the NTS induced: (1) increase in the neural firing response to intratracheal capsaicin application, (2) increase of endocannabinoid anandamide and palmitoylethanolamide, a reduction of 2-arachidonoylglycerol levels in the NTS, (3) glial cell activation, and (4) prevention by a Group III metabotropic glutamate receptor activation of neural firing response to intratracheal application of capsaicin in both naïve and sensitized rats. Therefore, normalization of ovalbumin-induced NTS neural sensitization could open up the prospect of new treatments based on the recovery of specific brain nuclei function and for extensive studies on acute or long-term efficacy of selective mGlu ligand, in models of bronchial hyperreactivity

Biomarkers of Inflammation and Lung recovery in ECMO patients with Persistent Pulmonary Hypertension of the Newborn (PPHN): A feasibility study

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Objectives: Extracorporeal membrane oxygenation is a treatment for Persistent Pulmonary Hypertension of the Newborn with high mortality. Hypothesis: the extracorporeal membrane oxygenation circuit results in inflammatory responses that mitigate against successful weaning. Design: Single-center prospective observational feasibility study. Setting: PICU. Patients: Twenty-four neonates requiring extracorporeal membrane oxygenation support for Persistent Pulmonary Hypertension of the Newborn. Interventions: None. Measurements and Main Results: The reference outcome was death or more than 7 days of extracorporeal membrane oxygenation support. Other outcomes included serial measures of plasma-free hemoglobin and markers of its metabolism, leucocyte, platelet and endothelial activation, and biomarkers of inflammation. Of 24 participants recruited between February 2016 and June 2017, 10 died or required prolonged extracorporeal membrane oxygenation support. These patients were sicker at baseline with higher levels of plasma-free hemoglobin within 12 hours of cannulation (geometric mean ratio, 1.92; 95% CIs, 1.00–3.67; p = 0.050) but not thereafter, versus those requiring less than 7 days extracorporeal membrane oxygenation. Serum haptoglobin concentrations were significantly elevated in both groups. Patients who died or required prolonged extracorporeal membrane oxygenation support demonstrated elevated levels of platelet-leucocyte aggregation, but decreased concentrations of mediators of the inflammatory response: interleukin-8, C-reactive protein, and tumor necrosis factor α. Conclusions: Clinical status at baseline and not levels of plasma-free hemoglobin or the systemic inflammatory response may determine the requirement for prolonged extracorporeal membrane oxygenation support in neonates

Deciphering the pathogenesis of tendinopathy: a three-stages process

Our understanding of the pathogenesis of "tendinopathy" is based on fragmented evidences like pieces of a jigsaw puzzle. We propose a "failed healing theory" to knit these fragments together, which can explain previous observations. We also propose that albeit "overuse injury" and other insidious "micro trauma" may well be primary triggers of the process, "tendinopathy" is not an "overuse injury" per se. The typical clinical, histological and biochemical presentation relates to a localized chronic pain condition which may lead to tendon rupture, the latter attributed to mechanical weakness. Characterization of pathological "tendinotic" tissues revealed coexistence of collagenolytic injuries and an active healing process, focal hypervascularity and tissue metaplasia. These observations suggest a failed healing process as response to a triggering injury. The pathogenesis of tendinopathy can be described as a three stage process: injury, failed healing and clinical presentation. It is likely that some of these "initial injuries" heal well and we speculate that predisposing intrinsic or extrinsic factors may be involved. The injury stage involves a progressive collagenolytic tendon injury. The failed healing stage mainly refers to prolonged activation and failed resolution of the normal healing process. Finally, the matrix disturbances, increased focal vascularity and abnormal cytokine profiles contribute to the clinical presentations of chronic tendon pain or rupture. With this integrative pathogenesis theory, we can relate the known manifestations of tendinopathy and point to the "missing links". This model may guide future research on tendinopathy, until we could ultimately decipher the complete pathogenesis process and provide better treatments

Chronic peripheral administration of serotonin inhibits thyroid function in the rat.

We studied the effect of chronic intraperitoneal (ip) administration of serotonin (5-HT) and thyroid function. We injected daily intraperitoneally for 10 days different doses of 5-HT, and measured plasma thyroid hormones and TSH levels. There was a decrease in the plasma levels of T3 and T4 with medium doses of 5-HT (0.2 and 0.4 mg/Kg bw for T3, and 0.2 for T4). No effects were evidenced on the plasma levels of TSH. In normal environmental conditions, the site action of 5-HT outside the blood-brain barrier is active when the 5-HT is injected at defined doses. This is probably a result of down-regulation independent of the hypothalamus-pituitary-thyroid axis

Deiodinating activity in the brown adipose tissue of rats following short cold exposure after strenuous exercise.

Interscapular brown adipose tissue (IBAT) activity is controlled by the sympathetic nervous system, and factors that influence thermogenesis appear to act centrally to modify the sympathetic outflow to IBAT. Cold exposure produces a rise in IBAT temperature as a result of the increase in sympathetic outflow to IBAT. This is associated with an increased thyroid activity. 3,5,3'-triiodothyronine (T3) and T4 levels increase during strenuous exercise, and, at the end of the exercise bout, a decrease of T3 and T4 levels, with an increase in TSH during the following 4-5 days, is seen. We evaluated the effect of strenuous exercise on 5'-deiodinase (5'-D) activity in IBAT in normal environmental conditions and after short (30 min) cold exposure. 5'-D activity is lower in rats at basal condition. Short cold exposure (SCE) increases 5'-D in IBAT both in exercising rats and in sedentary rats. However, this increase is lower in exercising animals. Strenuous exercise can reduce 5'-D activity in normal environmental conditions and after SCE. Probably, other compensatory mechanisms of heat production are active in exercising rodents

Serotonin effect on deiodinating activity in the rat.

Serotonin (5-HT) and thyroid hormones are part of a complex system modulating eating behaviour and energy expenditure. 5-Deiodinase (5-D) converts the relatively inactive thyroxine (T4) to triiodothyronine (T3), and its activity is an indirect measure of T3 production in peripheral tissues, particularly in the brain, intrascapular brown adipose tissue (IBAT), heart, liver, and kidney. We evaluated the effect of 5-HT on 5'-D activity during basal conditions and after short (30 min) cold exposure (thyroid stimulating hormone stimulation test, TST). 5'-D activity was assessed in the liver, heart, brain, kidney, and IBAT. TST increases 5'-D activity in the brain, heart, and IBAT and decreases it in kidney, leaving it unchanged in the liver. 5-HT alone did not modify 5'-D activity in the organs under study but decreased it in the IBAT, heart, and brain when injected before the TST was administered. Our results confirm the important role of 5-HT in thermoregulation, given its peripheral site of action, in modulating heat production controlling intracellular T3 production. These effects are more evident when heat production is upregulated during cold exposure in organs containing type II 5'-D, such as the brain, heart, and IBAT, which are able to modify their function during conditions that alter energy balance. In conclusion, 5-HT may also act peripherally directly on the thyroid and organs containing type II 5'-D, thus controlling energy expenditure through heat production