Actigraphy methodology in the Kids Mod PAH trial: Physical activity as a functional endpoint in pediatric clinical trials.

Pulmonary vasodilator treatment can improve hemodynamics, right ventricular function, symptoms, and survival in pediatric pulmonary hypertension (PH). However, clinical trial data are lacking due to many constraints. One major limitation is the lack of relevant trial endpoints reflective of hemodynamics or functional status in patients in whom standard exercise testing is impractical, unreliable, or not reproducible. The Kids Mod PAH trial (Mono- vs. Duo Therapy for Pediatric Pulmonary Arterial Hypertension) is an ongoing multicenter, Phase III, randomized, open-label, pragmatic trial to compare the safety and efficacy of first-line combination therapy (sildenafil and bosentan) to first-line monotherapy (sildenafil alone) in 100 pediatric patients with PH across North America. Investigators will measure participants' physical activity with a research-grade, wrist-worn actigraphy device at multiple time points as an exploratory secondary outcome. Vector magnitude counts per minute and activity intensity will be compared between the treatment arms. By directly and noninvasively measuring physical activity in the ambulatory setting, we aim to identify a novel, simple, inexpensive, and highly reproducible approach for quantitative assessment of exercise tolerance in pediatric PH. These data will increase the field's understanding of the effect of pulmonary vasodilator treatment on daily activity - a quantitative measure of functional status and wellbeing in pediatric PH and a potential primary outcome for future clinical trials in children with cardiopulmonary disorders.

The impact and recovery of asteroid 2018 LA.

The June 2, 2018, impact of asteroid 2018 LA over Botswana is only the second asteroid detected in space prior to impacting over land. Here, we report on the successful recovery of meteorites. Additional astrometric data refine the approach orbit and define the spin period and shape of the asteroid. Video observations of the fireball constrain the asteroid's position in its orbit and were used to triangulate the location of the fireball's main flare over the Central Kalahari Game Reserve. 23 meteorites were recovered. A consortium study of eight of these classifies Motopi Pan as a HED polymict breccia derived from howardite, cumulate and basaltic eucrite, and diogenite lithologies. Before impact, 2018 LA was a solid rock of ~156 cm diameter with high bulk density ~2.85 g/cm3, a relatively low albedo pv ~ 0.25, no significant opposition effect on the asteroid brightness, and an impact kinetic energy of ~0.2 kt. The orbit of 2018 LA is consistent with an origin at Vesta (or its Vestoids) and delivery into an Earth-impacting orbit via the v6 resonance. The impact that ejected 2018 LA in an orbit towards Earth occurred 22.8 ± 3.8 Ma ago. Zircons record a concordant U-Pb age of 4563 ± 11 Ma and a consistent 207Pb/206Pb age of 4563 ± 6 Ma. A much younger Pb-Pb phosphate resetting age of 4234 ± 41 Ma was found. From this impact chronology, we discuss what is the possible source crater of Motopi Pan and the age of Vesta's Veneneia impact basin.

Changes in fatigability following intense aerobic exercise training in patients with interstitial lung disease.

OBJECTIVE: To determine if, in patients with interstitial lung disease (ILD), fatigue might be lessened after vigorous aerobic exercise. METHODS: 13 physically inactive patients (5 men and 8 women; age 57.2 ± 9.1 years, BMI 28.2 ± 4.6 kgm(-2)) with ILD of heterogeneous etiology and able to walk on a motor driven treadmill without physical limitation were enrolled. Subjects underwent cardiopulmonary exercise (CPET) and 6-min walk (6MWT) tests and completed Fatigue Severity Scale and Human Activity Profile questionnaires before and after an aerobic exercise-training regimen. The training regimen required participation in at least 24 of 30 prescribed aerobic exercise training sessions at a target heart rate of 70-80% of the heart rate reserve, 30 min per session, 3 times per week for 10 weeks. RESULTS: After training, a 55% (p < 0.001) increase in time to anaerobic threshold on the CPET, and an 11% (p = 0.045) reduction in performance fatigability index (PFI), calculated from the performance on the 6MWT were observed. Distance walked on the 6MWT (6MWD) increased by 49.7 ± 46.9 m (p = 0.002). Significant improvements in scores on the Fatigue Severity Scale (p = 0.046) and Human Activity Profile (AAS p = 0.024; MAS p = 0.029) were also observed. No adverse events related to the training regimen were noted. CONCLUSION: After training, the decrease in fatigability appeared to result in increased 6MWD and was associated with physical activity. Since significant declines in 6MWD may be a marker for impending mortality in ILD, a better understanding of the etiological state of fatigue in patients with ILD and its reversal might provide fundamental insight into disease progression and even survival. [ClinicalTrials.gov identifier NCT00678821].

Improved Cardiorespiratory Fitness With Aerobic Exercise Training in Individuals With Traumatic Brain Injury.

OBJECTIVE: To examine cardiorespiratory fitness in individuals with traumatic brain injury (TBI), before and following participation in a supervised 12-week aerobic exercise training program. METHODS: Ten subjects with nonpenetrating TBI (TBI severity: mild, 50%; moderate, 40%; severe, 10%; time since injury [mean ± SD]: 6.6 ± 6.8 years) performed exercise training on a treadmill 3 times a week for 30 minutes at vigorous intensity (70%-80% of heart rate reserve). All subjects completed a cardiopulmonary exercise test, with pulmonary gas exchange measured and a questionnaire related to fatigue (Fatigue Severity Scale) at baseline and following exercise training. RESULTS: After training, increases (P < .01) in peak oxygen consumption ((Equation is included in full-text article.); +3.1 ± 2.4 mL/min/kg), time to volitional fatigue (+1.4 ± 0.8 minutes), and peak work rate (+59 ± 43 W) were observed. At the anaerobic threshold, (Equation is included in full-text article.)(+3.6 ± 2.1 mL/kg/min), treadmill time (+1.8 ± 1.1 minutes), and work rate (+37 ± 39 W) were higher (P < .01) following exercise training. Subjects also reported significantly lower (P < .05) Fatigue Severity Scale composite scores (-0.9 ± 1.3) following exercise training. CONCLUSION: These findings suggest that individuals with TBI may benefit from participation in vigorous aerobic exercise training with improved cardiorespiratory fitness and diminished fatigue.