Partitioning of respiration between the gills and air-breathing organ in response to aquatic hypoxia and exercise in the Pacific tarpon, Megalops cyprinoides

The evolution of air-breathing organs (ABOs) is associated not only with hypoxic environments but also with activity. This investigation examines the effects of hypoxia and exercise on the partitioning of aquatic and aerial oxygen uptake in the Pacific tarpon. The two-species cosmopolitan genus Megalops is unique among teleosts in using swim bladder ABOs in the pelagic marine environment. Small fish ( 58 - 620 g) were swum at two sustainable speeds in a circulating flume respirometer in which dissolved oxygen was controlled. For fish swimming at 0.11 m s(-1) in normoxia (Po-2 = 21 kPa), there was practically no air breathing, and gill oxygen uptake was 1.53 mL kg(-0.67) min(-1). Air breathing occurred at 0.5 breaths min(-1) in hypoxia ( 8 kPa) at this speed, when the gills and ABOs accounted for 0.71 and 0.57 mL kg(-0.67) min(-1), respectively. At 0.22 m s(-1) in normoxia, breathing occurred at 0.1 breaths min(-1), and gill and ABO oxygen uptake were 2.08 and 0.08 mL kg(-0.67) min(-1), respectively. In hypoxia and 0.22 m s(-1), breathing increased to 0.6 breaths min(-1), and gill and ABO oxygen uptake were 1.39 and 1.28 mL kg(-0.67) min(-1), respectively. Aquatic hypoxia was therefore the primary stimulus for air breathing under the limited conditions of this study, but exercise augmented oxygen uptake by the ABOs, particularly in hypoxic water.

Determinants of functional capacity in patients with chronic heart failure: Role of filling pressure and systolic and diastolic function

Background Previous work suggesting a better correlation of diastolic than systolic function with exercise capacity in heart failure may reflect the -relative insensitivity and load-dependence of ejection fraction (EF). We sought the correlation of new and more sensitive methods of quantifying systolic and diastolic function and filling pressure with functional capacity. Methods We studied 155 consecutive exercise tests on 95 patients with congestive heart failure (81 male, aged 62 +/- 10 years), who underwent resting 2-climensional echocardiography and tissue Doppler imaging before and after measurement of maximum oxygen uptake (peak VO2)Results The resting EF was 3 1 % 10% and a peak VO(2)was 13 +/- 5 mL/kg/min; the majority of these patients (80%) had an ischemic cardiornyopathy. Resting EF (r 0.14, P =.09) correlated poorly with peak VO2 and mean systolic (r = 0.23, P =.004) and diastolic tissue velocities (r 0.18, P =.02). Peak EF was weakly correlated with the mean systolic (r = 0.18, P =.02) and diastolic velocities (r = 0.16, P <.04). The mean sum of systolic and diastolic velocities in both annuli (r = 0.30, P <.001) and E/Ea ratio (r 0.31, P <.001) were better correlated with peak VO2 Prediction of peak VO2 was similar with models based on models of filling pressure (R = 0.61), systolic factors (R = 0.63), and diastolic factors (R 0.59), although a composite model of filling pressure, systolic and diastolic function was a superior predictor of peak VO2 (R 0.69; all P<.001). Conclusions The reported association of diastolic rather than systolic function with functional capacity may have reflected the limitations of EF. Functional capacity appears related not only to diastolic function, but also to systolic function and filling pressure, and is most closely associated with a combination of these factors.

Relationship between laboratory-measured variables and heart rate during an ultra-endurance triathlon

The aim of the present study was to examine the relationship between the performance heart rate during an ultra-endurance triathlon and the heart rate corresponding to several demarcation points measured during laboratory-based progressive cycle ergometry and treadmill running. Less than one month before an ultra-endurance triathlon, 21 well-trained ultra-endurance triathletes (mean +/- s: age 35 +/- 6 years, height 1.77 +/- 0.05 in, mass 74.0 +/- 6.9 kg, (V) over dot O-2peak = 4.75 +/- 0.42 1 center dot min(-1)) performed progressive exercise tests of cycle ergometry and treadmill running for the determination of peak oxygen uptake ((V) over do O-2peak), heart rate corresponding to the first and second ventilatory thresholds, as well as the heart rate deflection point. Portable telemetry units recorded heart rate at 60 s increments throughout the ultra-endurance triathlon. Heart rate during the cycle and run phases of the ultra-endurance triathlon (148 +/- 9 and 143 +/- 13 beats center dot min(-1) respectively) were significantly (P < 0.05) less than the second ventilatory thresholds (160 +/- 13 and 165 +/- 14 beats center dot min(-1) respectively) and heart rate deflection points (170 +/- 13 and 179 +/- 9 beats center dot min(-1) respectively). However, mean heart rate during the cycle and run phases of the ultra-endurance triathlon were significantly related to (r = 0.76 and 0.66; P < 0.01), and not significantly different from, the first ventilatory thresholds (146 +/- 12 and 148 +/- 15 beats center dot min(-1) respectively). Furthermore, the difference between heart rate during the cycle phase of the ultra-endurance triathlon and heart rate at the first ventilatory threshold was related to marathon run time (r = 0.61; P < 0.01) and overall ultra-endurance triathlon time (r = 0.45; P < 0.05). The results suggest that triathletes perform the cycle and run phases of the ultra-endurance triathlon at an exercise intensity near their first ventilatory threshold

Carbohydrate supplementation and alterations in neutrophils, and plasma cortisol and myoglobin concentration after intense exercise

The present study examined the effect of carbohydrate supplementation on changes in neutrophil counts, and the plasma concentrations of cortisol and myoglobin after intense exercise. Eight well-trained male runners ran on a treadmill for 1 h at 85% maximal oxygen uptake on two separate occasions. In a double-blind cross-over design, subjects consumed either 750 ml of a 10% carbohydrate (CHO) drink or a placebo drink on each occasion. The order of the trials was counterbalanced. Blood was drawn immediately before and after exercise, and I h after exercise. Immediately after exercise, neutrophil counts (CHO, 49%; placebo, 65%; P < 0.05), plasma concentrations of glucose (CHO, 43%; P

Strength and endurance training lead to different post exercise glucose profiles in diabetic participants using a continuous subcutaneous glucose monitoring system

Background Although both strength training (ST) and endurance training (ET) seem to be beneficial in type 2 diabetes mellitus (T2D), little is known about post-exercise glucose profiles. The objective of the study was to report changes in blood glucose (BG) values after a 4-month ET and ST programme now that a device for continuous glucose monitoring has become available. Materials and methods Fifteen participants, comprising four men age 56.5 +/- 0.9 years and 11 women age 57.4 +/- 0.9 years with T2D, were monitored with the MiniMed (Northridge, CA, USA) continuous glucose monitoring system (CGMS) for 48 h before and after 4 months of ET or ST. The ST consisted of three sets at the beginning, increasing to six sets per week at the end of the training period, including all major muscle groups and ET performed with an intensity of maximal oxygen uptake of 60% and a volume beginning at 15 min and advancing to a maximum of 30 min three times a week. Results A total of 17 549 single BG measurements pretraining (619.7 +/- 39.8) and post-training (550.3 +/- 30.1) were recorded, correlating to an average of 585 +/- 25.3 potential measurements per participant at the beginning and at the end of the study. The change in BG-value between the beginning (132 mg dL(-1)) and the end (118 mg dL(-1)) for all participants was significant (P = 0.028). The improvement in BG-value for the ST programme was significant (P = 0.02) but for the ET no significant change was measured (P = 0.48). Glycaemic control improved in the ST group and the mean BG was reduced by 15.6% (Cl 3-25%). Conclusion In conclusion, the CGMS may be a useful tool in monitoring improvements in glycaemic control after different exercise programmes. Additionally, the CGMS may help to identify asymptomatic hypoglycaemia or hyperglycaemia after training programmes.

Stoichiometric and kinetic characterisation of Nitrobacter in mixed culture by decoupling the growth and energy generation processes

The growth, maintenance and lysis processes of Nitrobacter were characterised. A Nitrobacter culture was enriched in a sequencing batch reactor (SBR). Fluorescent in situ hybridisation showed that Nitrobacter constituted 73% of the bacterial population. Batch tests were carried out to measure the oxygen uptake rate and/or nitrite consumption rate when both nitrite and CO2 were in excess, and in the absence of either of these two substrates. The results obtained, along with the SBR performance data, allowed the determination of the maintenance coefficient and in situ cell lysis rate of Nitrobacter. Nitrobacter spends a significant amount of energy for maintenance, which varies considerably with the specific growth rate. At maximum growth, Nitrobacter consume nitrite at a rate of 0.042 mgN/mgCOD(biomass)center dot h for maintenance purposes, which increases more than threefold to 0.143 mgN/mgCOD(biomass)center dot h in the absence of growth. In the SBR, where Nitrobacter grew at 40% of its maximum growth rate, a maintenance coefficient of 0.113 mgN/mgCOD center dot h was found, resulting in 42% of the total amount of nitrite being consumed for maintenance. The above three maintenance coefficient values obtained at different growth rates appear to support the maintenance model proposed in Pirt (1982). The in situ lysis rate of Nitrobacter was determined to be 0.07/day under aerobic conditions at 22 C and pH 7.3. Further, the maximum specific growth rate of Nitrobacter was estimated to be 0.02/h (0.48/day). The affinity constant of Nitrobacter with respect to nitrite was determined to be 1.50 mgNO(2)(-)-N/L, independent of the presence or absence of CO2. (c) 2006 Wiley Periodicals, Inc.

Stoichiometric and kinetic characterisation of Nitrosomonas sp in mixed culture by decoupling the growth and energy generation processes

A novel method that relies on the decoupling of the energy production and biosynthesis processes was used to characterise the maintenance, cell lysis and growth processes of Nitrosomonas sp. A Nitrosolnonas culture was enriched in a sequencing batch reactor (SBR) with ammonium as the sole energy source. Fluorescent in situ hybridization (FISH) showed that Nitrosomonas bound to the NEU probe constituted 82% of the bacterial population, while no other known ammonium or nitrite oxidizing bacteria were detected. Batch tests were carried out under conditions that both ammonium and CO, were in excess, and in the absence of one of these two substrates. The oxygen uptake rate and nitrite production rate were measured during these batch tests. The results obtained from these batch tests, along with the SBR performance data, allowed the determination of the maintenance coefficient and the in situ cell lysis rate, as well as the maximum specific growth rate of the Nitrosomonas culture. It is shown that, during normal growth, the Nitrosomonas culture spends approximately 65% of the energy generated for maintenance. The maintenance coefficient was determined to be 0.14 - 0.16 mgN mgCOD(biomass)(-1) h(-1), and was shown to be independent of the specific growth rate. The in situ lysis rate and the maximum specific growth rate of the Nitrosomonas culture were determined to be 0.26 and 1.0 day(-1) (0.043 h(-1)), respectively, under aerobic conditions at 30 degrees C and pH7. (c) 2006 Elsevier B.V. All rights reserved.

Contact lenses and sport

Contact lenses seem to be the ideal method of vision correction for ametropic people who participate in sporting activities. This thesis sets out to evaluate the viewpoint of the optometric professional and that of the patient on the use of contact lenses in sport and to establish if education is needed within this area. It also aims to provide some scientific evidence on the effect of exercise on the physiology of the cornea with and without contact lenses. Silicone hydrogel contact lenses have previously been suggested to impede heat dissipation from the cornea compared to mid water hydrogels. This was further demonstrated with exercise. The physiological integrity of the cornea is dependant on the amount of oxygen available to its surfaces. Contact lenses can disrupt the diffusion of oxygen to the cornea. Previous methods of measuring the oxygen consumption of the cornea have been limited by their invasive nature and assessment of only a small surface area of the cornea. They are not suitable to measure corneal oxygen consumption during exercise with and without contact lenses. A new method needed to be established. This was achieved by designing a novel method by the use of an oxygen sensor inside an airtight goggle using dynamic quenching of luminescence method. This established a non-contact way of measuring the effect oxygen uptake with and without contact lenses in vivo, allowing the contact lens to be undisturbed in their natural environment. The new method differentiated between the closed-eye and the open-eye condition with a good within-visit repeatability. It also illustrated that the cornea utilises oxygen at a faster rate during controlled aerobic exercise at moderate intensity. New contact lenses are available specifically for sport, these claim to reduce glare and increase contrast for daylight outdoor sports. However, visual benefits of these types of contact lenses cannot be measured easily in an indoor clinical environment, such as the optometric practice. To demonstrate any potential benefits of these lenses emulation of them should be conducted outdoors.

Global data compilation of benthic data sets II

In this study we present a global distribution pattern and budget of the minimum flux of particulate organic carbon to the sea floor (J POC alpha). The estimations are based on regionally specific correlations between the diffusive oxygen flux across the sediment-water interface, the total organic carbon content in surface sediments, and the oxygen concentration in bottom waters. For this, we modified the principal equation of Cai and Reimers [1995] as a basic monod reaction rate, applied within 11 regions where in situ measurements of diffusive oxygen uptake exist. By application of the resulting transfer functions to other regions with similar sedimentary conditions and areal interpolation, we calculated a minimum global budget of particulate organic carbon that actually reaches the sea floor of ~0.5 GtC yr**-1 (>1000 m water depth (wd)), whereas approximately 0.002-0.12 GtC yr**-1 is buried in the sediments (0.01-0.4% of surface primary production). Despite the fact that our global budget is in good agreement with previous studies, we found conspicuous differences among the distribution patterns of primary production, calculations based on particle trap collections of the POC flux, and J POC alpha of this study. These deviations, especially located at the southeastern and southwestern Atlantic Ocean, the Greenland and Norwegian Sea and the entire equatorial Pacific Ocean, strongly indicate a considerable influence of lateral particle transport on the vertical link between surface waters and underlying sediments. This observation is supported by sediment trap data. Furthermore, local differences in the availability and quality of the organic matter as well as different transport mechanisms through the water column are discussed.

Methane and sulphate consumption in different habitats of the Håkon Mosby Mud Volcano (HMMV)

The Hakon Mosby Mud Volcano is a highly active methane seep hosting different chemosynthetic communities such as thiotrophic bacterial mats and siboglinid tubeworm assemblages. This study focuses on in situ measurements of methane fluxes to and from these different habitats, in comparison to benthic methane and oxygen consumption rates. By quantifying in situ oxygen, methane, and sulfide fluxes in different habitats, a spatial budget covering areas of 10-1000 -m diameter was established. The range of dissolved methane efflux (770-2 mmol m-2 d-1) from the center to the outer rim was associated with a decrease in temperature gradients from 46°C to < 1°C m-1, indicating that spatial variations in fluid flow control the distribution of benthic habitats and activities. Accordingly, total oxygen uptake (TOU) varied between the different habitats by one order of magnitude from 15 mmol m-2 d-1 to 161 mmol m-2 d-1. High fluid flow rates appeared to suppress benthic activities by limiting the availability of electron acceptors. Accordingly, the highest TOU was associated with the lowest fluid flow and methane efflux. This was most likely due to the aerobic oxidation of methane, which may be more relevant as a sink for methane as previously considered in submarine ecosystems.

Seawater carbonate chemistry and combined physiological effects of CO2 and light on the N2-fixing cyanobacterium Trichodesmium IMS101 during experiments, 2010

Recent studies on the diazotrophic cyanobacterium Trichodesmium erythraeum(IMS101) showed that increasing CO2 partial pressure (pCO2) enhances N2 fixation and growth. Significant uncertainties remain as to the degree of the sensitivity to pCO2, its modification by other environmental factors, and underlying processes causing these responses. To address these questions, we examined the responses ofTrichodesmium IMS101 grown under a matrix of low and high levels of pCO2 (150 and 900 µatm) and irradiance (50 and 200 µmol photons m-2 s-1). Growth rates as well as cellular carbon and nitrogen contents increased with increasing pCO2 and light levels in the cultures. The pCO2-dependent stimulation in organic carbon and nitrogen production was highest under low light. High pCO2 stimulated rates of N2fixation and prolonged the duration, while high light affected maximum rates only. Gross photosynthesis increased with light but did not change with pCO2. HCO3- was identified as the predominant carbon source taken up in all treatments. Inorganic carbon uptake increased with light, but only gross CO2 uptake was enhanced under high pCO2. A comparison between carbon fluxes in vivo and those derived from 13C fractionation indicates high internal carbon cycling, especially in the low-pCO2treatment under high light. Light-dependent oxygen uptake was only detected underlow pCO2 combined with high light or when low-light-acclimated cells were exposed to high light, indicating that the Mehler reaction functions also as a photoprotective mechanism in Trichodesmium. Our data confirm the pronounced pCO2 effect on N2fixation and growth in Trichodesmium and further show a strong modulation of these effects by light intensity. We attribute these responses to changes in the allocation of photosynthetic energy between carbon acquisition and the assimilation of carbon and nitrogen under elevated pCO2. These findings are supported by a complementarystudy looking at photosynthetic fluorescence parameters of photosystem II, photosynthetic unit stoichiometry (photosystem I:photosystem II), and pool sizes of key proteins in carbon and nitrogen acquisition.

The adaptive response of humans to exercise: Impact of exercise intensity, fibre-type specific responses and molecular patterns of response

In an attempt to improve the current understanding of the adaptive response to exercise in humans, this dissertation performed a series of studies designed to examine the impact of training intensity and mode on aerobic capacity and performance, fibre-type specific adaptations to training, and individual patterns of response across molecular, morphological and genetic factors. Project #1 determined that training intensity, session dose, baseline VO2max and total training volume do not influence the magnitude of change in VO2max by performing a meta-regression, and meta-analysis of 28 different studies. The intensity of training had no effect on the magnitude of increase in maximal oxygen uptake in young healthy participants, but similar adaptations were achieved with lower training doses following high intensity training. Project # 2 determined the acute molecular response, and training-induced adaptations in aerobic performance, aerobic capacity and muscle phenotype following high-intensity interval training (HIT) or endurance exercise (END). The acute molecular response (fibre recruitment and signal activation) and training-induced adaptations in aerobic capacity, aerobic performance, and muscle phenotype were similar following HIT and END. Project # 3 examined the impact of baseline muscle morphology and molecular characteristics on the training response, and if muscle adaptations are coordinated. The muscle phenotype of individuals who experience the largest improvements (high responders) were lower before training for some muscle characteristics and molecular adaptations were coordinated within individual participants. Project # 4 examined the impact of 2 different intensities of HIT on the expression of nuclear and mitochondrial encoded genes targeted by PGC-1α. A systematic upregulation of nuclear and mitochondrial encoded genes was not present in the early recovery period following acute HIT, but the expression of mitochondrial genes were coordinated at an individual level. Collectively, results from the current dissertation contribute to our understanding of the molecular mechanisms influencing skeletal muscle and whole-body adaptive responses to acute exercise and training in humans.

A Group-Enhanced Sprint Interval Training Program for Amateur Athletes

Sprint interval training (SIT) can elicit improvements in aerobic and anaerobic capacity. While variations in SIT protocols have been investigated, the influence of social processes cannot be overlooked. As research supports the use of groups to influence individual cognitions and behaviours, the current project assessed the effectiveness of a group-based intervention with participants conducting SIT. Specifically, 53 amateur athletes (age, 21.9 ± 2.9 years; 53% females) took part in a 4-week training program (3 sessions per week, 30-s “all-out” efforts with 4 min active recovery, repeated 4–6 times per session), and were assigned to “true group”, aggregate, or individual conditions. Results indicated no significant differences between groups for the physiological measures. With regards to training improvements from baseline for all participants— regardless of condition — significant main effects for time were identified for maximal oxygen uptake (2.5–2.8 mL·kg−1·min−1, p < 0.001, η2 = 0.03), time-trial performance (14–32 s, p < 0.001, η2 = 0.37), and anaerobic power (1.1–1.7 k·h−1, p < 0.001, η2 = 0.66). With regards to the psychological measures, significant main effects between groups were found for motivation (p = 0.033, η2 = 0.13), task self-efficacy (p = 0.018, η2 = 0.15), and scheduling self-efficacy (p = 0.003, η2 = 0.22). The true group experienced greater improvements in motivation than the individual condition, but the aggregate and individual conditions demonstrated greater increases in task and scheduling self-efficacy. Though the SIT paradigm employed induced training improvements similar to previous work, the group intervention was not able to further these improvements

STRUCTURAL AND FUNCTIONAL CORRELATES OF EXERCISE VENTILATORY INEFFICIENCY IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS WITH MILD-TO-MODERATE SPIROMETRIC ABNORMALITIES

Background: Individuals with chronic obstructive pulmonary disease (COPD) have higher than normal ventilatory equivalents for carbon dioxide (VE/VCO2) during exercise. There is growing evidence that emphysema on thoracic computed tomography (CT) scans is associated with poor exercise capacity in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that emphysema is an underlying cause of microvascular dysfunction and ventilatory inefficiency, which in turn contributes to reduced exercise capacity. We expected ventilatory inefficiency to be associated with a) the extent of emphysema; b) lower diffusing capacity for carbon monoxide; c) a reduced pulmonary blood flow response to exercise; and d) reduced exercise capacity. Methods: In a cross-sectional study, 19 subjects with mild-to-moderate COPD (mean ± SD FEV1= 82 ± 13% predicted, 12 GOLD grade 1) and 26 age-, sex-, and activity-matched controls underwent a ramp-incremental symptom-limited exercise test on a cycle ergometer. Ventilatory inefficiency was assessed by the minimum VE/VCO2 value (nadir). A subset of subjects also completed repeated constant work rate exercise bouts with non-invasive measurements of pulmonary blood flow. Emphysema was quantified as the percentage of attenuation areas below -950 Housefield Units on CT scans. An electronic scoresheet was used to keep track of emphysema sub-types. Results: COPD subjects typically had centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/lower lobe ratio= 0.82 ± 0.04). They had lower peak oxygen uptake (VO2), higher VE/VCO2 nadir and greater dyspnea scores than controls (p<0.05). Lower peak O2 and worse dyspnea were found in COPD subjects with VE/VCO2 nadirs ≥ 30. COPD subjects had blunted increases in pulmonary blood flow from rest to iso-VO2 exercise (p<0.05). Higher VE/VCO2 nadir in COPD subjects correlated with emphysema severity (r= 0.63), which in turn correlated with reduced lung diffusing capacity (r= -0.72) and blunted changes in pulmonary blood flow from rest to exercise (r= -0.69) (p<0.01). Conclusions: Ventilation “wasted” in emphysematous areas is associated with reduced exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (gas transfer) to a key clinical outcome (reduced exercise capacity) in COPD patients with modest spirometric abnormalities.

The relationship between changes in cardiovascular function and changes in VO2peak following SIT

Background: It is well known that sprint interval training (SIT), induces significant increases in peak oxygen uptake (VO2peak) at the group level. However, there have been only a few studies that have addressed the variability of VO2peak response following SIT, and precise mechanism(s) that may explain individual magnitude of response are unknown. Purpose: Therefore, the purpose of this thesis was to: 1) examine the inter-individual variability of the VO2peak response following SIT, 2) to inspect the relationship between changes in both central and peripheral measures and changes in VO2peak, and 3) to assess if peripheral or central adaptations play a role in whether an individual is a high or low responder with respect to VO2peak. Subjects: Twenty-two young, recreationally active males (age: 20.4 1.7 years; weight: 78.4 10.2 kg; VO2peak: 3.7 0.62 L/min) Methods: VO2peak (L/min), peak cardiac output (Qpeak [L/min]), and peak deoxygenated hemoglobin (HHbpeak [mM]) were measured before and after 16 sessions of SIT (Tabata Protocol) over four weeks. Peak a-vO2diff was calculated using a derivation of the Fick equation. Results: Due to a systematic error, HHbpeak could not be used to differentiate between individual responses. There was a large range of VO2peak response from pre to post testing (-4.75 to 32.18% change) and there was a significant difference between the Low Response Group (LRG) (n=8) and the High Response Group (HRG) (n=8) [f(1, 14)= 64.27, p<0.001]. Furthermore, there was no correlation between delta () VO2peak and Qpeak (r=-0.18, p=0.46) for all participants, nor was there an interaction effect between the Low and High Response Groups [f(1,11)=0.572, p=0.47]. Lastly, there was a significant correlation between VO2peak and peak a-vO2diff [r=0.692, p<0.001], and a significant interaction effect with peak a-vO2diff [f(1, 14)= 13.27, p<0.004] when comparing the HRG to the LRG. Conclusions: There was inter-individual variability of VO2peak response following 4 weeks of SIT, but central adaptations did not influence this variation. This suggests that peripheral adaptations may be responsible for VO2peak adaptation.