Distributed Extremum-Seeking Control with Applications to High-Altitude Balloons

The real-time optimization of large-scale systems is a difficult problem due to the need for complex models involving uncertain parameters and the high computational cost of solving such problems by a decentralized approach. Extremum-seeking control (ESC) is a model-free real-time optimization technique which can estimate unknown parameters and can optimize nonlinear time-varying systems using only a measurement of the cost function to be minimized. In this thesis, we develop a distributed version of extremum-seeking control which allows large-scale systems to be optimized without models and with minimal computing power. First, we develop a continuous-time distributed extremum-seeking controller. It has three main components: consensus, parameter estimation, and optimization. The consensus provides each local controller with an estimate of the cost to be minimized, allowing them to coordinate their actions. Using this cost estimate, parameters for a local input-output model are estimated, and the cost is minimized by following a gradient descent based on the estimate of the gradient. Next, a similar distributed extremum-seeking controller is developed in discrete-time. Finally, we consider an interesting application of distributed ESC: formation control of high-altitude balloons for high-speed wireless internet. These balloons must be steered into a favourable formation where they are spread out over the Earth and provide coverage to the entire planet. Distributed ESC is applied to this problem, and is shown to be effective for a system of 1200 ballons subjected to realistic wind currents. The approach does not require a wind model and uses a cost function based on a Voronoi partition of the sphere. Distributed ESC is able to steer balloons from a few initial launch sites into a formation which provides coverage to the entire Earth and can maintain a similar formation as the balloons move with the wind around the Earth.

High altitude journeys and flights are associated with the increased risk of flares in IBD patients

Background: There is increasing evidence that hypoxia induces inflammation in the gastrointestinal tract. The clinical impact of hypoxia in patients with inflammatory bowel disease (IBD) is so far poorly investigated. Aim: We wanted to evaluate if flights and journeys to regions >= 2000 meter above sea level are associated with the occurrence of flares in IBD patients in the following 4 weeks. Methods: A questionnaire was completed by inpatients and outpatients of the IBD clinics of three tertiary referral centers presenting with an IBD flare. Patients were inquired about their habits in the 4 weeks prior to the flare. Patients with flares were matched with an IBD group in remission during the observation period (according to age, gender, smoking habits, and medication). Results: A total of 103 IBD patients were included (43 Crohn's disease (CD), whereof 65% female, 60 ulcerative colitis, whereof 47% female, mean age 39.3 ± 14.6 years for CD and 43.1 ± 14.2 years for UC). Fifty-two patients with flares were matched to 51 patients without flare. Overall, IBD-patients with flares had significantly more frequently a flight and/or journey to regions >= 2000 meters above sea level in the observation period compared to the patients in remission (21/52 (40.4%) vs. 8/51 (15.7%), p = 0.005). There was a statistically significant correlation between the occurrence of a flare and a flight and/or journey to regions >= 2000 meters above sea level among CD patients with flares as compared to CD patients in remission (8/21 (38.1%) vs. 2/22 (9.1%), p = 0.024). A trend for more frequent flights and high-altitude journeys was observed in UC patients with flares (13/31 (41.9%) vs. 6/29 (20.7%), p = 0.077). Mean flight duration was 5.8 ± 4.3 hours. The groups were controlled for the following factors (always flare group cited first): age (39.6 ± 13.4 vs. 43.5 ± 14.6, p = 0.102), smoking (16/52 vs. 10/51, p = 0.120), regular sports activities (32/52 vs. 33/51, p = 0.739), treatment with antibiotics in the 4 weeks before flare (8/52 vs. 7/51, p = 0.811), NSAID intake (12/52 vs. 7/51, p = 0.221), frequency of chronic obstructive pulmonary disease (both groups 0) and oxygen therapy (both groups 0). Conclusion: IBD patients with a flare had significantly more frequent flights and/or high-altitude journeys within four weeks prior to the IBD flare compared to the group that was in remission. We conclude that flights and stays in high altitude are a risk factor for IBD flares.

Exhaled nitric oxide in high-altitude pulmonary edema: role in the regulation of pulmonary vascular tone and evidence for a role against inflammation.

High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed subjects at altitudes above 2,500 m. It is not clear whether, in addition to hemodynamic factors and defective alveolar fluid clearance, inflammation plays a pathogenic role in HAPE. We therefore made serial measurements of exhaled pulmonary nitric oxide (NO), a marker of airway inflammation, in 28 HAPE-prone and 24 control subjects during high-altitude exposure (4,559 m). To examine the relationship between pulmonary NO synthesis and pulmonary vascular tone, we also measured systolic pulmonary artery pressure (Ppa). In the 13 subjects who developed HAPE, exhaled NO did not show any tendency to increase during the development of lung edema. Throughout the entire sojourn at high altitude, pulmonary exhaled NO was roughly 30% lower in HAPE-prone than in control subjects, and there existed an inverse relationship between Ppa and exhaled NO (r = -0.51, p < 0.001). These findings suggest that HAPE is not preceded by airway inflammation. Reduced exhaled NO may be related to altered pulmonary NO synthesis and/or transport and clearance, and the data in our study could be consistent with the novel concept that in HAPE-prone subjects, a defect in pulmonary epithelial NO synthesis may contribute to exaggerated hypoxic pulmonary vasoconstriction and in turn to pulmonary edema.

High altitude, a natural research laboratory for the study of cardiovascular physiology and pathophysiology.

High altitude constitutes an exciting natural laboratory for medical research. Although initially, the aim of high-altitude research was to understand the adaption of the organism to hypoxia and find treatments for altitude-related diseases, during the past decade or so, the scope of this research has broadened considerably. Two important observations led the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema represents a unique model that allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Second, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we will review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.

Effects of added dead space on sleep disordered breathing at high altitude

Introduction: Sleep disordered breathing with central apnea or hypopnea frequently occurs during sleep at high altitude. The aim of this study was to assess the effects of added dead space (DS) on sleep disordered breathing and transcutaneous CO2 (PtcCO2) level during sleep at high altitude. Methods: Full night sleep recordings were obtained on 12 unacclimatized mountaineers (11 males, 1 female, mean age 39 ± 12 y.o.) during one of the first 4 nights after arrival in Leh, Ladakh (3500 m). In random order, half of the night was spent with a 500 ml increase in dead space through a custom designed full face mask and the other half without it. PtcCO2 was measured in 3 participants. Results: Baseline recordings reveled two clearly distinct groups: one with severe sleep disordered breathing (n = 5) and the other with mild or no disordered breathing (n = 7). Added dead space markedly improved breathing in the first group (baseline vs DS): apnea hypopnea index (AHI) 70.3 ± 25.8 vs 29.4 ± 6.9 (p = 0.013), oxygen desaturation index (ODI): 72.9 ± 24.1/h vs 42.5 ± 14.4 (p = 0.031), whereas it had no significant effect in the second group. Added dead space did not have a significant effect on mean oxygen saturation level. Respiratory events were almost exclusively central apnea or hypopnea except for one subject. Only a minor increase in mean PtcCO2 (n = 3) was observed: 33.6 ± 1.8 mm Hg at baseline and 35.0 ± 2.62 mm Hg with DS. Sleep quality was preserved under dead space condition, since the microarousal rate remained unchanged (16.8 ± 8.7/h vs 19.4 ± 18.6/h (p = 0.51). Conclusion: In mountaineers with severe sleep disordered breathing at high altitude, a 500 ml increase in dead space through a fitted mask significantly improves nocturnal breathing.

High altitude journeys and flights are associated with the increased risk of flares in IBD patients

Background: There is increasing experimental evidence that hypoxia induces inflammation in the gastrointestinal tract. Hypoxia-inducible transcription factor (HIF)-1α influences adaptive immunity and has been shown to induce barrier-protective genes in the case of experimentally-induced colitis. The clinical impact of hypoxia in patients with inflammatory bowel disease (IBD) is so far poorly investigated. Aim: We wanted to evaluate if flights and journeys to regions ≥2000 meter above sea level are associated with the occurrence of flares in IBD patients in the following 4 weeks. Methods: A questionnaire was completed by inpatients and outpatients of the IBD clinics of three tertiary referral centers presenting with an IBD flare in the period from Sept 1st 2009 to August 31st 2010. Patients were inquired about their habits in the 4 weeks prior to the flare. Patients with flares were matched with an IBD group in remission during the observation period (according to age, gender, smoking habits, and medication). Results: A total of 103 IBD patients were included (43 Crohn's disease (CD), whereof 65% female, 60 ulcerative colitis, whereof 47% female, mean age 39.3±14.6 years for CD and 43.1±14.2 years for UC). Fifty-two patients with flares were matched to 51 patients without flare. Overall, IBD-patients with flares had significantly more frequently a flight and/or journey to regions ≥ 2000 meters above sea level in the observation period compared to the patients in remission (21/52 (40.4%) vs. 8/51 (15.7%), p=0.005). There was a statistically significant correlation between the occurrence of a flare and a flight and/or journey to regions ≥ 2000 meters above sea level among CD patients with flares as compared to CD patients in remission (8/21 (38.1%) vs. 2/22 (9.1%), p=0.024). A trend for more frequent flights and high-altitude journeys was observed in UC patients with flares (13/31 (41.9%) vs. 6/29 (20.7%), p=0.077). Mean flight duration was 5.8±4.3 hours. The groups were controlled for the following factors (always flare group cited first): age (39.6±13.4 vs. 43.5±14.6, p=0.102), smoking (16/52 vs. 10/51, p=0.120), regular sports activities (32/ 52 vs. 33/51, p=0.739), treatment with antibiotics in the 4 weeks before flare (8/52 vs. 7/ 51, p=0.811), NSAID intake (12/52 vs. 7/51, p=0.221), frequency of chronic obstructive pulmonary disease (both groups 0) and oxygen therapy (both groups 0). Conclusion: IBD patients with a flare had significantly more frequent flights and/or high-altitude journeys within four weeks prior to the IBD flare compared to the group that was in remission. We conclude that flights and stays in high altitude are a risk factor for IBD flares.

Characterization of modern and fossil mineral dust transported to high altitude in the Western Alps: Saharan sources and transport patterns

Mineral dust aerosols recently collected at the high-altitude Jungfraujoch research station (46 degrees 33'51 `' N, 7 degrees 59'06 `' E; 3580 m a.s.l.) were compared to mineral dust deposited at the Colle Gnifetti glacier (45 degrees 52'50 `' N, 7 degrees 52'33 `' E; 4455 m a.s.l.) over the last millennium. Radiogenic isotope signatures and backward trajectories analyses indicate that major dust sources are situated in the north-central to north-western part of the Saharan desert. Less radiogenic Sr isotopic compositions of PM10 aerosols and of mineral particles deposited during periods of low dust transfer likely result from the enhancement of the background chemically-weathered Saharan source. Saharan dust mobilization and transport were relatively reduced during the second part of the Little Ice Age (ca. 1690-1870) except within the greatest Saharan dust event deposited around 1770. After ca. 1870, sustained dust deposition suggests that increased mineral dust transport over the Alps during the last century could be due to stronger spring/summer North Atlantic southwesterlies and drier winters in North Africa. On the other hand, increasing carbonaceous particle emissions from fossil fuel combustion combined to a higher lead enrichment factor point to concomitant anthropogenic sources of particulate pollutants reaching high-altitude European glaciers during the last century.

High altitude journeys and flights are associated with an increased risk of flares in inflammatory bowel disease patients.

BACKGROUND AND AIMS: Hypoxia can induce inflammation in the gastrointestinal tract. However, the impact of hypoxia on the course of inflammatory bowel disease (IBD) is poorly understood. We aimed to evaluate whether flights and/or journeys to regions lying at an altitude of >2000 m above the sea level are associated with flare-ups within 4 weeks of the trip. METHODS: IBD patients with at least one flare-up during a 12-month observation period were compared to a group of patients in remission. Both groups completed a questionnaire. RESULTS: A total of 103 IBD patients were included (43 with Crohn's disease (CD): mean age 39.3 ± 14.6 years; 60 with ulcerative colitis (UC): mean age 40.4 ± 15.1 years). Fifty-two patients with flare-ups were matched to 51 patients in remission. IBD patients experiencing flare-ups had more frequently undertaken flights and/or journeys to regions >2000 m above sea level within four weeks of the flare-up when compared to patients in remission (21/52 [40.4%] vs. 8/51 [15.7%], p=0.005). CONCLUSIONS: Journeys to high altitude regions and/or flights are a risk factor for IBD flare-ups occurring within 4 weeks of travel.

Pulmonary-artery pressure and exhaled nitric oxide in Bolivian and Caucasian high altitude dwellers.

There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler chocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean+/-SD systolic right ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg) and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

Effect of added dead space on sleep disordered breathing at high altitude.

OBJECTIVE: Sleep disordered breathing with central apnea or hypopnea frequently occurs at high altitude and is thought to be caused by a decrease in blood CO(2) level. The aim of this study was to assess the effects of added respiratory dead space on sleep disordered breathing.¦METHODS: Full polysomnographies were performed on 12 unacclimatized swiss mountaineers (11 males, 1 female, mean age 39±12 y.o.) in Leh, Ladakh (3500m). In random order, half of the night was spent with a 500ml increase in dead space through a custom designed full face mask and the other half without it.¦RESULTS: Baseline data revealed two clearly distinct groups: one with severe sleep disordered breathing (n=5, AHI>30) and the other with moderate to no disordered breathing (n=7, AHI<30). DS markedly improved breathing in the first group (baseline vs DS): apnea hypopnea index (AHI) 70.3±25.8 vs 29.4±6.9 (p=0.013), oxygen desaturation index (ODI): 72.9±24.1/h vs 42.5±14.4 (p=0.031), whereas it had no significant effect in the second group or in the total population. Respiratory events were almost exclusively central apnea or hypopnea. Microarousal index, sleep efficiency, and sleep architecture remained unchanged with DS. A minor increase in mean PtcCO(2) (n=3) was observed with DS.¦CONCLUSION: A 500ml increase in dead space through a fitted mask may improve nocturnal breathing in mountaineers with severe altitude-induced sleep disordered breathing.

New insights in the pathogenesis of high-altitude pulmonary edema.

High-altitude pulmonary edema is a life-threatening condition occurring in predisposed but otherwise healthy individuals. It therefore permits the study of underlying mechanisms of pulmonary edema in the absence of confounding factors such as coexisting cardiovascular or pulmonary disease, and/or drug therapy. There is evidence that some degree of asymptomatic alveolar fluid accumulation may represent a normal phenomenon in healthy humans shortly after arrival at high altitude. Two fundamental mechanisms then determine whether this fluid accumulation is cleared or whether it progresses to HAPE: the quantity of liquid escaping from the pulmonary vasculature and the rate of its clearance by the alveolar respiratory epithelium. The former is directly related to the degree of hypoxia-induced pulmonary hypertension, whereas the latter is determined by the alveolar epithelial sodium transport. Here, we will review evidence that, in HAPE-prone subjects, impaired pulmonary endothelial and epithelial NO synthesis and/or bioavailability may represent a central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and, in turn, capillary stress failure and alveolar fluid flooding. We will then demonstrate that exaggerated pulmonary hypertension, although possibly a conditio sine qua non, may not always be sufficient to induce HAPE and how defective alveolar fluid clearance may represent a second important pathogenic mechanism.

Respiratory nitric oxide and pulmonary artery pressure in children of aymara and European ancestry at high altitude.

Invasive studies suggest that healthy children living at high altitude display pulmonary hypertension, but the data to support this assumption are sparse. Nitric oxide (NO) synthesized by the respiratory epithelium regulates pulmonary artery pressure, and its synthesis was reported to be increased in Aymara high-altitude dwellers. We hypothesized that pulmonary artery pressure will be lower in Aymara children than in children of European ancestry at high altitude, and that this will be related to increased respiratory NO. We therefore compared pulmonary artery pressure and exhaled NO (a marker of respiratory epithelial NO synthesis) between large groups of healthy children of Aymara (n = 200; mean +/- SD age, 9.5 +/- 3.6 years) and European ancestry (n = 77) living at high altitude (3,600 to 4,000 m). We also studied a group of European children (n = 29) living at low altitude. The systolic right ventricular to right atrial pressure gradient in the Aymara children was normal, even though significantly higher than the gradient measured in European children at low altitude (22.5 +/- 6.1 mm Hg vs 17.7 +/- 3.1 mm Hg, p < 0.001). In children of European ancestry studied at high altitude, the pressure gradient was 33% higher than in the Aymara children (30.0 +/- 5.3 mm Hg vs 22.5 +/- 6.1 mm Hg, p < 0.0001). In contrast to what was expected, exhaled NO tended to be lower in Aymara children than in European children living at the same altitude (12.4 +/- 8.8 parts per billion [ppb] vs 16.1 +/- 11.1 ppb, p = 0.06) and was not related to pulmonary artery pressure in either group. Aymara children are protected from hypoxic pulmonary hypertension at high altitude. This protection does not appear to be related to increased respiratory NO synthesis.

Humic Haplustox under different land uses in a high altitude environment in the Agreste region of Pernambuco, Brazil

The Garanhuns Plateau in the Agreste region of the State of Pernambuco, Brazil is characterized by humid climatic conditions due to orographic rains, unlike the surrounding semiarid region. These soils are subjected to intense agricultural use and are extremely important for the regional economy. This study was carried out in the municipality of Brejão in the Agreste region with the aim of assessing changes in humic Haplustox soils subjected to different land uses. Four plots with different vegetation covers (native forest, secondary shrubby vegetation (capoeira), traditional cropping system, and planted pasture) were selected, and samples were taken from a soil profile and four small pits surrounding it at each site. Physical and chemical properties were assessed, including aggregate stability, humic organic fractions, and a microbiological evaluation through determination of basal respiration, microbial biomass carbon, and metabolic quotient. The soils under study showed physical and chemical properties typical of a Haplustox, such as low nutrient content, low cation exchange capacity, and high levels of acidity and Al saturation. The total organic carbon (TOC) contents were high regardless of the type of land use. Aggregates < 2 mm were dominant in all the conditions under study. The TOC content was higher in the soil under capoeira, 43.91 g kg-1 on the surface, while 34.36 and 33.43 g kg-1 of TOC were observed in the first layer of forest and pasture soils, respectively. While the microbial biomass C (MBC) was greater than 700 mg kg-1 in the forest and pasture areas (in the 0-5 cm layer), and 588 mg kg-1 in the soil under capoeira, these numbers were not statistically different. In the cultivated soil area, there was a reduction of around 28 % in TOC and MBC contents. Agricultural activity contributed to degradation of the humic horizon, as can be seen from a significant decrease in the TOC and changes in the relative distribution of the humic fractions. In contrast, aggregate stability was not altered as a function of the different land uses; the soil under planted pasture and capoeira were similar to the soil under native forest. Humin was the most important humified fraction for C reserves, contributing over 40 % of the TOC in these soils.