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The cardinal symptom of pulmonary hypertension (PH) is dyspnea on exertion, leading to decreased activity in daily living. The aim of this study was to analyze daily physical activity in incident patients with arterial or chronic thromboembolic PH (PAH/CTEPH) and to investigate its correlation with pulmonary hemodynamics, symptoms, exercise capacity, and other outcomes. Incident patients with PAH/CTEPH had a 1-week activity assessment by the arm-worn accelerometer SenseWear within − 3 months/+ 2 weeks of the diagnostic right heart catheterization (RHC) and baseline assessments including 6-minute walking distance (6MWD). Activity was correlated to RHC data at rest and exercise and to other outcomes. Thirty-nine PH-patients (24 PAH, 15 CTEPH, 23 females, 65(54;73) years, mean pulmonary artery pressure (mPAP) 38(30;46) mmHg, cardiac output (CO) 5.2(4.6;6.3) l/min, 6MWD 458(300;593) m) were included. 64% had a sedentary lifestyle (

IntroductionWe investigated whether nocturnal oxygen therapy (NOT) mitigates the increase of pulmonary artery pressure in patients during daytime with chronic obstructive pulmonary disease (COPD) traveling to altitude.MethodsPatients with COPD living below 800 m underwent examinations at 490 m and during two sojourns at 2,048 m (with a washout period of 2 weeks < 800 m between altitude sojourns). During nights at altitude, patients received either NOT (3 L/min) or placebo (ambient air 3 L/min) via nasal cannula according to a randomized crossover design. The main outcomes were the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography on the second day at altitude (under ambient air) and various other echocardiographic measures of the right and left heart function. Patients fulfilling predefined safety criteria were withdrawn from the study.ResultsTwenty-three COPD patients [70% Global Initiative for Chronic Obstructive Lung Disease (GOLD) II/30% GOLD III, mean ± SD age 66 ± 5 years, FEV1 54% ± 13% predicted] were included in the per-protocol analysis. TRPG significantly increased when patients traveled to altitude (from low altitude 21.7 ± 5.2 mmHg to 2,048 m placebo 27.4 ± 7.3 mmHg and 2,048 m NOT 27.8 ± 8.3 mmHg) difference between interventions (mean difference 0.4 mmHg, 95% CI −2.1 to 3.0, p = 0.736). The tricuspid annular plane systolic excursion was significantly higher after NOT vs. placebo [2.6 ± 0.6 vs. 2.3 ± 0.4 cm, mean difference (95% confidence interval) 0.3 (0.1 − 0.5) cm, p = 0.005]. During visits to 2,048 m until 24 h after descent, eight patients (26%) using placebo and one (4%) using NOT had to be withdrawn because of altitude-related adverse health effects (p < 0.001).ConclusionIn lowlanders with COPD remaining free of clinically relevant altitude-related adverse health effects, changes in daytime pulmonary hemodynamics during a stay at high altitude were trivial and not modified by NOT.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT02150590.

There are no established measures to prevent nocturnal breathing disturbances and other altitude-related adverse health effects (ARAHEs) among lowlanders with chronic obstructive pulmonary disease (COPD) traveling to high altitude.To evaluate whether nocturnal oxygen therapy (NOT) prevents nocturnal hypoxemia and breathing disturbances during the first night of a stay at 2048 m and reduces the incidence of ARAHEs.This randomized, placebo-controlled crossover trial was performed from January to October 2014 with 32 patients with COPD living below 800 m with forced expiratory volume in the first second of expiration (FEV1) between 30% and 80% predicted, pulse oximetry of at least 92%, not requiring oxygen therapy, and without history of sleep apnea. Evaluations were performed at the University Hospital Zurich (490 m, baseline) and during 2 stays of 2 days and nights each in a Swiss Alpine hotel at 2048 m while NOT or placebo treatment was administered in a randomized order. Between altitude sojourns, patients spent at least 2 weeks below 800 m. Data analysis was performed from January 1, 2015, to December 31, 2018.During nights at 2048 m, NOT or placebo (room air) was administered at 3 L/min by nasal cannula.Coprimary outcomes were differences between NOT and placebo intervention in altitude-induced change in mean nocturnal oxygen saturation (SpO2) as measured by pulse oximetry and apnea-hypopnea index (AHI) measured by polysomnography during night 1 at 2048 m and analyzed according to the intention-to-treat principle. Further outcomes were the incidence of predefined ARAHE, other variables from polysomnography results and respiratory sleep studies in the 2 nights at 2048 m, clinical findings, and symptoms.Of the 32 patients included, 17 (53%) were women, with a mean (SD) age of 65.6 (5.6) years and a mean (SD) FEV1 of 53.1% (13.2%) predicted. At 490 m, mean (SD) SpO2 was 92% (2%) and mean (SD) AHI was 21.6/h (22.2/h). At 2048 m with placebo, mean (SD) SpO2 was 86% (3%) and mean (SD) AHI was 34.9/h (20.7/h) (P .001 for both comparisons). Compared with placebo, NOT increased SpO2 by a mean of 9 percentage points (95% CI, 8-11 percentage points; P .001), decreased AHI by 19.7/h (95% CI, 11.4/h-27.9/h; P .001), and improved subjective sleep quality measured on a visual analog scale by 9 percentage points (95% CI, 0-17 percentage points; P = .04). During visits to 2048 m or within 24 hours after descent, 8 patients (26%) using placebo and 1 (4%) using NOT experienced ARAHEs (P .001).Lowlanders with COPD experienced hypoxemia, sleep apnea, and impaired well-being when staying at 2048 m. Because NOT significantly mitigated these undesirable effects, patients with moderate to severe COPD may benefit from preventive NOT during high altitude travel.ClinicalTrials.gov Identifier: NCT02150590.

Aims The purpose of the current trial was to test the hypothesis that breathing oxygen-enriched air increases exercise performance of patients with pulmonary arterial or chronic thrombo-embolic pulmonary hypertension (PAH/CTEPH) and to investigate involved mechanisms. Methods and results Twenty-two patients with PAH/CTEPH, eight women, means ± SD 61 ± 14 years, resting mPAP 35 ± 9mmHg, PaO2 ambient air >7.3 kPa, underwent four bicycle ergospirometries to exhaustion on different days, while breathing oxygen-enriched (FiO2 0.50, hyperoxia) or ambient air (FiO2 0.21, normoxia) using progressively increased or constant load protocols (with 75% maximal work rate under FiO2 0.21), according to a randomized, sham-controlled, single-blind, cross-over design. ECG, pulmonary gas-exchange, arterial blood gases, cerebral and quadriceps muscle tissue oxygenation (CTO and QMTO) by near-infrared spectroscopy were measured. In ramp exercise, maximal work rate increased from 113 ± 38 W with normoxia to 132 ± 48 W with hyperoxia, mean difference 19.7 (95% CI 10.5–28.9) W, P Conclusion In patients with PAH/CTEPH, breathing oxygen-enriched air provides major increases in exercise performance. This is related to an improved arterial oxygenation that promotes oxygen availability in muscles and brain and to a reduction of the excessive ventilatory response to exercise thereby enhancing ventilatory efficiency. Patients with PAH/CTEPH may therefore benefit from oxygen therapy during daily physical activities and training. Trial registration clinicaltrials.gov Identifier: NCT01748474.

Background: Patients with chronic obstructive pulmonary disease (COPD) experience dyspnea and hypoxemia during exercise. Objective: The aim of this study was to evaluate the effects of breathing oxygen-enriched air on exercise performance and associated physiological changes in patients with COPD. Methods: In a randomized, placebo-controlled, single-blind, cross-over trial, 20 patients with COPD (11 women, age 65 ± 6 years, FEV1 64 ± 19% pred., resting SpO2 ≥90%) performed 4 cycle ergospirometries to exhaustion using an incremental exercise test (IET) and a constant work rate (at 75% maximal workload with air) exercise test (CWRET), each with ambient (FiO2 0.21) and oxygen-enriched (FiO2 0.5) air. The main outcomes were the change in maximal workload in the IET and the change in exercise duration in the CWRET with oxygen versus air. Electrocardiogram, pulmonary gas exchange, thoracic volumes by inductance plethysmography, arterial blood gases, and cerebral and quadriceps muscle tissue oxygenation (CTO and MTO) were additionally measured. Results: In the IET, maximal workload increased from 96 ± 21 to 104 ± 28 W with oxygen. In the CWRET, exercise duration increased from 605 ± 274 to 963 ± 444 s with oxygen. At end-exercise with oxygen, CTO, MTO, PaO2, and PaCO2 were increased, while V’E/V’CO2 was reduced and thoracic volumes were similar. At the corresponding time to end of exercise with ambient air, oxygen decreased heart rate, respiratory rate, minute ventilation, and V’E/V’CO2, while oxygenation was increased. Conclusion: In COPD patients without resting hypoxemia, breathing oxygen-enriched air improves exercise performance. This relates to a higher arterial oxygen saturation promoting oxygen availability to muscle and cerebral tissue and an enhanced ventilatory efficiency. COPD patients may benefit from oxygen therapy during exercise training.

Introduction: Data about the influence of body position on hemodynamics is rare. Aims and Objective: To compare pulmonary hemodynamics at rest and exercise during right heart catheterization (exRHC) in supine and upright position. Methods: Retrospective analysis of adults undergoing exRHC due to suspected pulmonary hypertension (PH), with cohort A undergoing supine exRHC and cohort B supine and upright exRHC. We compared supine vs. upright resting hemodynamics within subjects of B overall and by subgroups. We compared supine vs. upright hemodynamics at rest and at exercise between precapillary PH cohort A & B. Results: 270 resp. 213 patients underwent exRHC in A/B (63/60% female, age 60±15/61±15 years, 52/31 no PH, 68/38 exercise PH, 126/120 pre-capillary PH, 24/24 post-capillary PH). The table shows supine and upright resting and exercise hemodynamics. Conclusion: Body position affects resting and exercise pulmonary hemodynamics. At rest in the overall population, all pressures and the cardiac index are lower in the upright versus supine position. Exercise hemodynamics in patients with precapillary PH revealed a similar maximal cardiac index, despite a higher workload and higher transpulmonary gradient (lower pulmonary arterial wedge pressure and higher mean pulmonary artery pressure) in the upright versus supine position and despite similar resting hemodynamics.

Background: The impact of hyperoxia on exercise limitation is still incompletely understood. Objectives: We investigated to which extent breathing hyperoxia enhances the exercise performance of healthy subjects and which physiologic mechanisms are involved. Methods: A total of 32 healthy volunteers (43 ± 15 years, 12 women) performed 4 bicycle exercise tests to exhaustion with ramp and constant-load protocols (at 75% of the maximal workload [Wmax] on FiO2 0.21) on separate occasions while breathing ambient (FiO2 0.21) or oxygen-enriched air (FiO2 0.50) in a random, blinded order. Workload, endurance, gas exchange, pulse oximetry (SpO2), and cerebral (CTO) and quadriceps muscle tissue oxygenation (QMTO) were measured. Results: During the final 15 s of ramp exercising with FiO2 0.50, Wmax (mean ± SD 270 ± 80 W), SpO2 (99 ± 1%), and CTO (67 ± 9%) were higher and the Borg CR10 Scale dyspnea score was lower (4.8 ± 2.2) than the corresponding values with FiO2 0.21 (Wmax 257 ± 76 W, SpO2 96 ± 3%, CTO 61 ± 9%, and Borg CR10 Scale dyspnea score 5.7 ± 2.6, p < 0.05, all comparisons). In constant-load exercising with FiO2 0.50, endurance was longer than with FiO2 0.21 (16 min 22 s ± 7 min 39 s vs. 10 min 47 s ± 5 min 58 s). With FiO2 0.50, SpO2 (99 ± 0%) and QMTO (69 ± 8%) were higher than the corresponding isotime values to end-exercise with FiO2 0.21 (SpO2 96 ± 4%, QMTO 66 ± 9%), while minute ventilation was lower in hyperoxia (82 ± 18 vs. 93 ± 23 L/min, p < 0.05, all comparisons). Conclusion: In healthy subjects, hyperoxia increased maximal power output and endurance. It improved arterial, cerebral, and muscle tissue oxygenation, while minute ventilation and dyspnea perception were reduced. The findings suggest that hyperoxia enhanced cycling performance through a more efficient pulmonary gas exchange and a greater availability of oxygen to muscles and the brain (cerebral motor and sensory neurons).

Introduction: Altitude travel in patients with COPD may be hampered by limitation in exercise performance but the extent and underlying physiological mechanisms have not been conclusively studied. Objective: To evaluate exercise performance in patients with COPD living below 600m travelling to 2048m. Methods 29 COPD patients, GOLD grade 2-3, mean±SD aged 65±6y, FEV1 59±13%pred. underwent bicycle spiroergometry with an identical ramp protocol to exhaustion at 490m (Zurich) and, within 2h after rapid ascent, at 2048m (St. Moritz). Physiological variables during the final 30sec of exercise were compared between altitudes. Results: Altitude-induced hypoxemia at 2048m reduced maximal work rate and oxygen uptake while heart rate, breathing reserve, and dyspnoea did not change (table). Conclusions: Ascent to 2048m, an altitude corresponding to that of many alpine resorts, reduced exercise performance of lowlanders with COPD only slightly. Since neither breathing nor heart rate reserve were altered, the altitude-induced performance impairment may have been due to effects of hypoxia on dyspnoea perception and muscle function rather than due to aggravated ventilatory or cardiovascular constraints. Grant: Swiss National Science Foundation, Lunge Zurich.

Background: Pulmonary hypertension (PH) leads to reduced health-related quality of life (HRQoL). Objective: To investigate the prevalence and course of anxiety and depression and their association with HRQoL, disease severity and survival in PH. Methods: 131 PH patients (91 pulmonary arterial, 30 chronic thromboembolic, 10 due to lung disease; 84 female, 47 male) had repeated assessments with the Hospital Anxiety and Depression Scale (HADS), HRQoL, six-minute walk distance and WHO functional class during a mean course of 16 ± 12 months. Results: Among the 49 incident and 82 prevalent PH patients, the HADS score was positive in 53%/21% (depression), 51%/24% (anxiety) and 63%/26% (total score) (all p < 0.05). The HADS score was improved at the second assessment in incident patients. The HADS score correlated with HRQoL at all consecutive assessments and with functional class until the third assessment, but not with baseline hemodynamics, age or gender. Conclusion: Mood disorders remain underdiagnosed in PH. The higher prevalence of anxiety/depression in incident versus prevalent patients and the improvement over time may indicate an amelioration of mood disorders after PH diagnosis and treatment.

Background: Patients with pulmonary hypertension (PH) may suffer from cognitive deficits that potentially relate to reduced oxygen delivery and cerebral tissue oxygenation (CTO). Objective: To evaluate the hypothesis that cognitive function improves with therapy, along with improved CTO. Methods: Twenty incident patients with arterial or chronic thromboembolic PH had CTO monitoring by near-infrared spectroscopy during diagnostic right heart catheterization. Cognitive tests [Trail Making Tests (TMTs), Victoria Stroop tests and the Five-Point Test (5PT)], the 6-min walk distance (6MWD) test, New York Heart Association (NYHA) class and health-related quality of life (HRQoL) were assessed and repeated after 3 months of disease-targeted medication. Results: At baseline, 45% of PH patients had cognitive deficits. At 3 months, the patients had improved on the TMT A and the Stroop 2 test [37 s (27; 55) versus 30 s (24; 42), p < 0.05, and 18 s (16; 22) versus 16 s (15; 20), p < 0.01], whereas CTO remained unchanged. Arterial oxygen saturation, NYHA class, 6MWD and HRQoL had also improved. Baseline CTO was the strongest predictor of cognitive function, even in multivariate analysis including age, 6MWD and HRQoL. Improvements in cognitive function were not associated with changes in CTO. Conclusions: In patients with PH, 3 months of disease-targeted medication resulted in better cognitive function. Although CTO was the strongest predictor of cognitive function at baseline, it did not change during target therapy. The results of this pilot study should be confirmed in an adequately powered controlled trial.

We tested whether long-term oxygen therapy (LTOT) at home would improve exercise capacity and quality of life in exercise-desaturating patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH). In this randomized, sham-controlled, double-blind, cross-over trial PAH/CTEPH-patients with exercise desaturation (resting PaO2>7.3 kPa) were recruited. They received either LTOT or sham air for 5 weeks (2-3l/min via nasal cannula, during nights and daytime rest, 9-13h/day) according to a randomized cross-over design, with 2 weeks wash-out in between. Co-primary outcomes were the 6-minute walking distance (6MWD) and the SF-36 physical component summary score (PCS). 30 patients (14/16 PAH/CTEPH, age 60±15y, BMI 28±6kg/m2, 6MWD 484±117m, mPAP 39±11mmHg) pretreated with endothelin-receptor antagonists (60%) and/or phosphodiesterase-5-inhibitors (43%) were randomized. There was a significant treatment effect of oxygen on the 6MWD (figure), whereas the effect on the PCS was non-significant.

BACKGROUND Sleep-disordered breathing may impair cerebral oxygenation in patients with OSA syndrome, in particular during altitude travel. We studied cerebral tissue oxygenation (CTO) at low and moderate altitude in patients with OSA and evaluated whether acetazolamide improved CTO. METHODS Eighteen patients with OSA living at RESULTS At 490 m, medians of CTO, peripheral oxygen saturation as measured by pulse oximetry (Sp o 2 ), and apnea/hypopnea index were 65%, 93%, and 57.3/h, respectively. At 2,590 m, on placebo, the corresponding values were 59%, 86%, and 86.4/h, respectively ( P o 2 at 2,590 m by mean values of 2% (95% CI, 0%-4%) and 2% (95% CI, 1%-3%), respectively, and reduced the apnea/hypopnea index by 23.4/h (95% CI, 14.0-32.8/h) ( P CONCLUSIONS In patients with OSA staying at altitude, nocturnal cerebral and arterial oxygenation were reduced in association with exacerbated sleep apnea. Acetazolamide partially improved CTO, Sp o 2 , and sleep apnea without impairing the cerebral blood flow response to apneas. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00714740; URL: www.clinicaltrials.gov

Study questionWe investigated whether domiciliary oxygen therapy (DOXT) increases exercise capacity and quality of life in patients with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension (PAH/CTEPH) presenting with mild resting hypoxaemia and exercise-induced oxygen desaturation.Materials and methods30 patients with PAH/CTEPH, mean±sdage 60±15 years, pulmonary artery pressure 39±11 mmHg, resting arterial oxygen saturation measured by pulse oximetry (SpO2) ≥90%,SpO2drop during a 6-min walk test ≥4%, on pulmonary hypertension-targeted medication, were randomised in a double-blind crossover protocol to DOXT and placebo (ambient air) treatment, each over 5 weeks, at 3 L·min−1vianasal cannula overnight and when resting during the day. Treatment periods were separated by 2 weeks of washout. Co-primary outcomes were changes in 6-min walk distance (6MWD, breathing ambient air) and physical functioning scale of the 36-item short-form medical outcome questionnaire during treatment periods.ResultsDOXT increased the 6MWD from baseline 478±113 m by a mean (95% CI) of 19 (6–32) m, and physical functioning from 52±29 by 4 (0–8) points. Corresponding changes with placebo were 1 (−11–13) m in 6MWD and −2 (−6–2) points in physical functioning. Between-treatment differences in changes were 6MWD 18 (1–35) m (p=0.042) and physical functioning 6 (1–11) points (p=0.029). DOXT significantly improved the New York Heart Association functional classversusplacebo.Answer to the questionThis first randomised trial in PAH/CTEPH patients with exercise-induced hypoxaemia demonstrates that DOXT improves exercise capacity, quality of life and functional class. The results support large long-term randomised trials of DOXT in PAH/CTEPH.

Purpose: Pulmonary hypertension (PH) due to COPD has dismal prognosis. We reviewed the long-term effect of PH-target therapy in severe PH-COPD. Method: Patients attending our PH-clinic were reviewed for PH-COPD receiving PH-target therapy. Baseline characteristics, death/transplantation until 2014, therapy, NYHA functional class, 6min walk distance (6MWD) and oxygen saturation (SpO2) at baseline, 3, 6, 12 and 24months were analysed. Results: Of 48 PH-COPD identified 21 were excluded (insufficient data, comorbidity). 27 patients (7 females, 21 smokers, 23 emphysema) with median (quartiles) baseline age 70 (60; 76)years, FEV1 60 (46; 78)%, FEV1/FVC 57 (51; 64)%, DLCO 42 (36; 59)%, mean pulmonary artery pressure 39 (32;44) mmHg under inhaled iloprost (10), subcutaneous prostanoids (2), intravenous prostanoids (3), endothelin receptor antagonists (15) and phosphodiesterase-5-inhibitors (25) were included. Under therapy, NYHA functional class improved from 3.5 (3; 4) to 3 (2; 4) after 3months and 3 (2; 3.5) after 6months (p=.02 and .008). The 6MWD improved from 373 (236; 452) to 395 (339; 472), 414 (285; 492) and 396 (308; 497)m at 3, 6 and 12months (p=.005, .006 and .011) with unchanged resting-SpO2 but decreased peak-exercise SpO2. During median follow-up of 5.9 (2.3; 8.4) years, 10 died, 2 were transplanted and 2 were lost to follow-up. Transplant-free survival at 1,2,3years was 92,69,54% and was similar for GOLD stages 1-4, but worse for patients with mPAP ≥40mmHg (p=.026), 6MWD

Pulmonary hypertension (PH) impairs oxygen delivery and exercise capacity. Aims: To investigate whether hyperoxia improves exercise performance in PAH or CTEPH. Methods: 22 stable PAH/CTEPH patients (8 women, 61±14y, mPAP 35±10mmHg) underwent 4 bicycle ergospirometries to exhaustion breathing FiO2 0.5 or air (FiO2 0.21) and using progressive or constant load (75%Wmax, FiO2 0.21) protocols, according to a randomized, cross-over design. Gas-exchange, SpO2, cerebral (CTO) and muscle (MTO) tissue oxygenation were monitored. Results: In progressive ramp tests under FiO2 0.5, Wmax, VO2max, SpO2, CTO and MTO exceed values during FiO2 0.21 at end-exercise, while VE/VCO2 and heart rate were reduced at isotime. In constant load tests with FiO2 0.5 endurance was increased by 210±223% vs. FiO2 0.21. Conclusions: In PAH/CTEPH, breathing FiO2 0.5 increases exercise performance by improving ventilatory efficiency and arterial oxygenation thereby enhancing oxygen availability in muscles and brain. Therefore, hyperoxia holds promise to improve efficacy of exercise training in PAH/CTEPH patients undergoing rehabilitation.

Patients with COPD may be severely limited in daily life but exercise tests may not adequately reflect this limitation. Aim: To assess whether daily activity correlates with exercise capacity and nocturnal oxygen saturation in COPD. Methods: COPD patients underwent activity monitoring (Sensewear TM ), maximal bicycle exercise test (CPET), 6 minute walk distance (6MWD) and ambulatory respiratory sleep study. Senswear TM derived activity was quantified by steps/day, daily estimated energy expenditure (EE) and average of metabolic equivalents (METs) per day. Pearson correlations of activity with exercise parameters or sleep were calculated. Results: 20 COPD patients (11 female, age 65±6y, FEV1 64±19%pred) were recruited. Patients were moderately active (7120±3492 steps/day), estimated EE was 9166±1085kJ and METs 1.4±0.2. Mean nocturnal oxygen saturation was 92±2%, oxygen desaturation index was 4.4±4.6. The steps/day correlated with FEV1%pred (r=0.51, p Conclusion: Patients with less severe airflow obstructions show higher daily activity. Daily activity measurements recorded in COPD provide important information, complementary to lung function, CPET and 6MWD since activity recordings estimate EE over several days in the setting of the patients9 everyday life. Daytime and nocturnal ventilation and oxygenation differently affect activity derived estimates of EE.

Mechanisms of exercise limitation in COPD are incompletely understood. Aim: To study the effects of hyperoxia on exercise performance, gas exchange, cerebral & muscle tissue oxygenation (CTO/MTO). Methods: 20 COPD (65±6y, FEV1 64±19%pred.) performed 4 CPET to exhaustion breathing FiO2 0.5 or 0.21 and using progressive or constant load (75%Wmax, FiO2 0.21) protocols monitoring gas-exchange, SpO2, CTO/MTO and hyperinflation (randomized, cross-over). Results: In progressive ramp test with FiO2 0.5, Wmax, VO2, SpO2, CTO/MTO exceed values during FiO2 0.21, while the VE/VCO2 and heart rate were reduced. Dynamic hyperinflation was irrespective of FiO2 and negatively correlated with constant load endurance on FiO2 0.5 (r=-0.54, p

Background: Pulmonary vascular diseases primary manifests with impaired exercise tolerance. We hypothesized that exercise pulmonary hemodynamics predict outcome in arterial and inoperable chronic thromboembolic pulmonary hypertension (PAH, CTEPH). Methods: Right heart catheterizations from PAH and CTEPH with hemodynamic assessment during supine step-wise cycle exercise (10 Watt/3min) were analyzed. Patients were closely followed and time of death or transplantation noted. Transplant-free survival and predictive value of hemodynamics were assessed by Kaplan Meier and Cox regression. Results: 70 patients (43 female, age 61±15y, 54PAH, 16CTEPH, mean 6 minute walk distance (6MWD) 444±130m, pulmonary artery pressure (mPAP) 37±10mmHg, cardiac output (CO) 5.5±1.8l/min were followed 18-3489d (median 610d). 1, 3, 5, 7 year survival was 89, 80, 71, 59%. Age, NYHA, 6MWD, mixed venous oxygen saturation but not resting hemodynamics predicted transplant-free survival. Power output and cardiac index at maximal exercise achieved (p-value;HR(95%CI): .027;.94(.89-.99) and .034;.51(.27-.95), change in cardiac index (.040;.25(06-.94) such as multipoint mPAP/CO and mPAP-increase/Watt were predictive variables of transplant-free survival (.003;1.02(1.01-1.03) and .038;3.47(1.07-11.25). mPAP/CO slope best predicted survival when corrected for age (HR 1.01, p=.042) and was a favorable predictor when Conclusion: In PAH and CTEPH, cardiac index increase and multipoint pressure-flow relationship during exercise were predictive for transplant-free survival. RHC performed in the diagnosis and management of PH should include measurements during both rest and exercise.

Background: Pulmonary hypertension (PH) leads to reduced health related quality of life (HRQoL) and possibly anxiety and depression, both potentially underdiagnosed and undertreated in PH. We investigated the prevalence and course of anxiety and depression and their association with HRQoL, disease markers and survival. Methods: 45 newly diagnosed and 86 pretreated patients with arterial and chronic thromboembolic PH (PAH and CTEPH, n=131, 84 females, 61 idiopathic) had repeated assessments of the Hospital Anxiety and Depression Scale (HADS), HRQoL, 6 minute walking distance (6MWD) and NYHA functional class during a mean course of 16±12 months. Depression/anxiety was diagnosed if HADS subscale was >5 or total >9. Results: 14.5% of PH-patients had previously been diagnosed with and treated for depression and had higher HADS. According to HADS, 33% of PH-patients suffered from depression with a mean score of 9±3 and 34% had anxiety (9±2.5). Of these patients, 38% were in treatment for their depression or anxiety. In incident patients, both scores improved 6±4 months after the introduction of PH-targeted treatment (p=0.009 and 0.007 respectively). HADS correlated with all domains of HRQoL, NYHA class and 6MWD but not with baseline hemodynamic parameters, age and gender. Survival was worse in patients with anxiety (p=0.014). Conclusions: Psychological morbidity remains underdiagnosed in PH. One third of patients suffer from depression and/or anxiety for which only 38% are being treated. PH-treatment improves mental symptoms in some PH-patients.

We derive the first six coefficients of the heat kernel expansion for the electromagnetic field in a cavity by relating it to the expansion for the Laplace operator acting on forms. As an application we verify that the electromagnetic Casimir energy is finite., 12 pages

We show that the positive supersymmetric matrix-valued differential operator H = p x 2 + p y 2 + x2y2 + xσ3 + yσ1 has no zero modes, i.e., Hψ = 0 implies ψ = 0. The result depends on a virial type argument for the corresponding supercharge. The model may be regarded as a simple relative of dimensional reductions of supersymmetric Yang–Mills theories.

BACKGROUND Sleep-disturbed breathing (SDB) is common in patients with precapillary pulmonary hypertension (PH). Nocturnal oxygen therapy (NOT) and acetazolamide improve SDB in patients with PH, and NOT improves exercise capacity. We investigated the effect of NOT and acetazolamide on nocturnal cardiac conduction, repolarization, and arrhythmias in patients with PH and SDB. METHODS In a randomized, placebo-controlled, double-blind, crossover trial, 23 patients with arterial (n = 16) or chronic thromboembolic PH (n = 7) and SDB defined as a mean nocturnal oxygen saturation 3%) > 10/h with daytime Pa o 2 ≥ 7.3 kPa were studied. Participants received NOT (3 L/min), acetazolamide tablets (2 × 250 mg), and sham-NOT/placebo each during 1 week separated by a 1-week washout period. Three-lead ECG was recorded during overnight polysomnography at the end of each treatment period. Repolarization indices were averaged over three cardiac cycles at late evening and at early morning, and nocturnal arrhythmias were counted. RESULTS NOT was associated with a lower overnight (68 ± 10 beats/min vs 72 ± 9 beats/min, P = .010) and early morning heart rate compared with placebo. At late evening, the heart rate-adjusted PQ time was increased under acetazolamide compared with placebo (mean difference, 10 milliseconds; 95% CI, 0-20 milliseconds; P = .042). In the morning under NOT, the heart rate-adjusted QT (QTc) interval was decreased compared with placebo (mean difference, −25 milliseconds; 95% CI, −45 to −6 milliseconds; P = .007), and the interval between the peak and the end of the T wave on the ECG was shorter compared with acetazolamide (mean difference, −11 milliseconds; 95% CI, −21 to −1 milliseconds; P = .028). Arrhythmias were rare and similar with all treatments. CONCLUSIONS In patients with PH with SDB, NOT reduces nocturnal heart rate and QTc in the morning, thus, favorably modifying prognostic markers. TRIAL REGISTRY: ClinicalTrials.gov ; No.: NTC-01427192; URL: www.clinicaltrials.gov

Warum besitzen heute viel weniger junge Manner einen eigenen Pkw als dies noch bis zum Jahr 2000 der Fall war? ‚Kuruma Banare‘ ist das japanische Schlagwort fur diese Entwicklung, die in Japan zwar zuerst beobachtet und belegt wurde, aber inzwischen auch fur Deutschland bestatigt werden kann: Der Anteil der Pkw-Halter in der Gruppe der jungen Manner zwischen 18 bis unter 30 Jahre ist in den vergangenen Jahrzehnten dramatisch gesunken: Wahrend fur die Jahre zwischen 1982 und 1991 Zahlen des Kraftfahrtbundesamtes belegen, dass etwa die Halfte der betrachteten Altersgruppe der Manner Pkw-Halter waren (1982: 48%; 1994: 59,8%), ist diese Zahl in der Altersgruppe „18 bis unter 30 Jahre“ der Manner – nach statistisch bedingten Ausschlagen durch das Einfliesen der Daten aus den Neuen Bundeslandern ab 1992 sowie den Datenausschluss vorrubergehend stillgelegter Fahrzeuge (Saison-Kennzeichen) aus den KBA-Bestandsziffern im Wechsel von 2007 auf 2008 – auf unter 30% gesunken (2011: 27,1%) [10]. Diese Entwicklung verweist auf Veranderungen im Lebensstil junger Manner und ihren Praferenzen zur individuellen Mobilitat. Parallel zu dieser Entwicklung der Pkw- Halterquoten hat sich auch die Zahl der jungen Manner in der betrachteten Altersgruppe verandert.

To hasten the process of saving lives after disasters in urban areas, autonomous robots are being looked to for providing mapping, hazard identification and casualty location. These robots need to maximise time in the field without having to recharge and without reducing productivity. This project aims to improve autonomous robot navigation through allowing comparison of algorithms with various weightings, in conjunction with the ability to vary physical parameters of the robot and other factors such as error thresholds/limits. The lack of a priori terrain data in disaster sites, means that robots have to dynamically create a representation of the terrain from received sensor range-data in order to path plan. To reduce the resources used, the affect of input data on the terrain model is analysed such that some points may be culled. The issues of identifying hazards within these models are considered with respect to the affect on safe navigation.

Background Pulmonary hypertension manifests with impaired exercise capacity. Our aim was to investigate whether the mean pulmonary arterial pressure to cardiac output relationship (mPAP/CO) predicts transplant-free survival in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Methods Hemodynamic data according to right heart catheterization in patients with PAH and CTEPH at rest and during supine incremental cycle exercise were analyzed. Transplant-free survival and predictive value of hemodynamics were assessed by using Kaplan-Meier and Cox regression analyses. Results Seventy patients (43 female; 54 with PAH, 16 with CTEPH; median (quartiles) age, 65 [50; 73] years; mPAP, 34 [29; 44] mm Hg; cardiac index, 2.8 [2.3; 3.5] [L/min]/m 2 ) were followed up for 610 (251; 1256) days. Survival at 1, 3, 5, and 7 years was 89%, 81%, 71%, and 59%. Age, World Health Organization-functional class, 6-min walk test, and mixed-venous oxygen saturation (but not resting hemodynamics) predicted transplant-free survival. Maximal workload (hazard ratio [HR], 0.94 [95% CI, 0.89-0.99]; P = .027), peak cardiac index (HR, 0.51 [95% CI, 0.27-0.95]; P = .034), change in cardiac index, 0.25 [95% CI, 0.06-0.94]; P = .040), and mPAP/CO (HR, 1.02 [95% CI, 1.01-1.03]; P = .003) during exercise predicted survival. Values for mPAP/CO predicted 3-year transplant-free survival with an area under the curve of 0.802 (95% CI, 0.66-0.95; P = .004). Conclusions In this collective of patients with PAH or CTEPH, the pressure-flow relationship during exercise predicted transplant-free survival and correlated with established markers of disease severity and outcome. Right heart catheterization during exercise may provide important complementary prognostic information in the management of pulmonary hypertension.

Each fieldbus device contains an internal set of data relevant mainly for automation and control tasks, but also suitable for maintenance purpose. In addition, other device-related data are available outside the device, like descriptions, instructions, or even pictures and multimedia files. Thus, the device can be treated as central part of a complex information set. This information set is used by software tools throughout a device's life cycle, e.g. configuration, commissioning, parameterization, diagnosis, repair, firmware update, asset management, audit trailing, etc. The paper describes an extensible, flexible, distributed Web-based information platform and presents an application example for PROFIBUS/PROFINET systems

We derive the power law decay, and asymptotic form, of SU(2) x Spin(d) invariant wave-functions which are zero-modes of all s_d=2(d-1) supercharges of reduced (d+1)-dimensional supersymmetric SU(2) Yang Mills theory, resp. of the SU(2)-matrix model related to supermembranes in d+2 dimensions., Comment: LaTeX, 18 pages Introduction amended

Background: Data on exercise pulmonary hemodynamics in healthy people and patients with pulmonary hypertension (PH) are rare. We analyzed exercise right heart catheterization (RHC) data in a symptomatic collective referred with suspected PH to characterize the differential response by diagnostic groups, to correlate resting with exercise hemodynamics, and to evaluate safety. Methods: This is a retrospective single-center study reviewing data from patients in whom an exercise RHC was performed between January 2006 and January 2013. Patients with follow-up RHC under PH -therapy were excluded. Results: Data from 101 patients were analyzed, none of them had an adverse event. In 35% we detected a resting PH (27.8% precapillary, 6.9% postcapillary). Exercise PH (mean pulmonary arterial pressure (mPAP) >30 mmHg at exercise) was found in 38.6%, whereas in 25.7% PH was excluded. We found a remarkable number of exercise PH in scleroderma patients, the majority being postcapillary. 83% of patients with mPAP-values between 20 and 24.9 mmHg at rest had exercise PH. Patients with resting PH had worse hemodynamics and were older compared with exercise PH ones. Conclusion: In this real-life experience in symptomatic patients undergoing exercise RHC for suspected PH, we found that exercise RHC is safe. The facts that the vast majority of patients with mPAP-values between 20 and 24.9 mmHg at rest had exercise PH and the older age of patients with resting PH may indicate that exercise PH is a precursor of resting PH. Whether earlier treatment start in patients with exercise PH would stabilize the disease should be addressed in future studies.

(1975). Seasonal changes in the response of Mysis relicta Loven to illumination. SIL Proceedings, 1922-2010: Vol. 19, No. 4, pp. 2989-3000.

Forty-three adult sockeye salmon (Oncorhynchus nerka) fitted with ultrasonic transmitters were tracked in coastal waters near the Fraser River in July and August, 1967 and 1968. Movement patterns of individual fish were unpredictable. Some moved actively in appropriate directions, some drifted passively, still others travelled southward away from their presnmed destination. Fish released in pairs did not travel along similar paths. Active fish moved generally northward toward the Fraser River, keeping away from shore and following axes of tidal currents. There was little straying into bays and channnels with slow currents. Some fish remained active both during the day and at night, while others became inactive after sunset or when the sun was not visible behind clouds. Average ground speed was about 1 body length/s (61 cm/s). Orientation to geoelectric fields is postulated, along with a compass-related orientation northward.

To test the olfactory hypothesis of salmon homing, fingerling coho salmon (Oncorhynchus kisutch) were exposed to low concentrations of an odorous synthetic chemical, morpholine during presmolt and smolting periods. Equal numbers of these fish were not exposed (controls). Both groups were stocked directly into Lake Michigan near Oak Creek, South Milwaukee Wisconsin. Another paired group of exposed and unexposed fish was released 13 km north of Oak Creek. During the adult spawning migration 18 mo later, morpholine was dripped into Oak Creek and the returning salmon were censused.For four experiments over 2 consecutive yr, the number of exposed and unexposed fish captured at the artificially scented stream were, 216 vs. 28, 437 vs. 49, 647 vs. 65, and 439 vs. 55. These differences were highly significant (P .05). These results confirm the existence of odor imprinting and long-term olfactory memory in coho salmon, It is possible that this mechanism is also used in the natural imprinting situation.

We compared the homing ability of three groups of rainbow trout (Salmo gairdneri) stocked in Lake Michigan by different procedures. One group of juvenile rainbow trout was imprinted to a synthetic chemical, morpholine, during the presmolt and smolt stages, and a second group was not imprinted. Both groups were stocked directly into Lake Michigan, 1 km north of the Little Manitowoc River. A third group of trout was retained in a pond on the Little Manitowoc River during the presmolt and smolt stages and then released into Lake Michigan at the same location as the other two groups. During the adult spawning migration, morpholine was metered into the Little Manitowoc River. This river and 16 other locations were monitored for returning fish. The morpholine-imprinted fish returned to the Little Manitowoc River in greater numbers and strayed less than did fish from the other two treatment groups. This result is a consequence of exposure to a unique odor cue at the critical period for imprinting.