Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks.

Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF ascertainment methods to establish, validate and characterize a proteomic CRF score. In a cohort of around 22,000 individuals in the UK Biobank, a proteomic CRF score was associated with a reduced risk of all-cause mortality (unadjusted hazard ratio 0.50 (95% confidence interval 0.48-0.52) per 1 s.d. increase). The proteomic CRF score was also associated with multisystem disease risk and provided risk reclassification and discrimination beyond clinical risk factors, as well as modulating high polygenic risk of certain diseases. Finally, we observed dynamicity of the proteomic CRF score in individuals who undertook a 20-week exercise training program and an association of the score with the degree of the effect of training on CRF, suggesting potential use of the score for personalization of exercise recommendations. These results indicate that population-based proteomics provides biologically relevant molecular readouts of CRF that are additive to genetic risk, potentially modifiable and clinically translatable.

Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study.

BACKGROUND: The association of fitness with cancer risk is not clear. METHODS: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. RESULTS: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min-1⋅kg-1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73-0.89), colorectal (0.94, 0.90-0.99), and breast cancer (0.96, 0.92-0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min-1⋅kg-1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86-0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. DISCUSSION: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.

Causal associations between cardiorespiratory fitness and type 2 diabetes.

Higher cardiorespiratory fitness is associated with lower risk of type 2 diabetes. However, the causality of this relationship and the biological mechanisms that underlie it are unclear. Here, we examine genetic determinants of cardiorespiratory fitness in 450k European-ancestry individuals in UK Biobank, by leveraging the genetic overlap between fitness measured by an exercise test and resting heart rate. We identified 160 fitness-associated loci which we validated in an independent cohort, the Fenland study. Gene-based analyses prioritised candidate genes, such as CACNA1C, SCN10A, MYH11 and MYH6, that are enriched in biological processes related to cardiac muscle development and muscle contractility. In a Mendelian Randomisation framework, we demonstrate that higher genetically predicted fitness is causally associated with lower risk of type 2 diabetes independent of adiposity. Integration with proteomic data identified N-terminal pro B-type natriuretic peptide, hepatocyte growth factor-like protein and sex hormone-binding globulin as potential mediators of this relationship. Collectively, our findings provide insights into the biological mechanisms underpinning cardiorespiratory fitness and highlight the importance of improving fitness for diabetes prevention.

Resting heart rate is a population-level biomarker of cardiorespiratory fitness: The Fenland Study.

INTRODUCTION: Few large studies have evaluated the relationship between resting heart rate (RHR) and cardiorespiratory fitness. Here we examine cross-sectional and longitudinal relationships between RHR and fitness, explore factors that influence these relationships, and demonstrate the utility of RHR for remote population monitoring. METHODS: In cross-sectional analyses (The UK Fenland Study: 5,722 women, 5,143 men, aged 29-65y), we measured RHR (beats per min, bpm) while seated, supine, and during sleep. Fitness was estimated as maximal oxygen consumption (ml⋅min-1⋅kg-1) from an exercise test. Associations between RHR and fitness were evaluated while adjusting for age, sex, adiposity, and physical activity. In longitudinal analyses (6,589 participant subsample), we re-assessed RHR and fitness after a median of 6 years and evaluated the association between within-person change in RHR and fitness. During the coronavirus disease-2019 pandemic, we used a smartphone application to remotely and serially measure RHR (1,914 participant subsample, August 2020 to April 2021) and examined differences in RHR dynamics by pre-pandemic fitness level. RESULTS: Mean RHR while seated, supine, and during sleep was 67, 64, and 57 bpm. Age-adjusted associations (beta coefficients) between RHR and fitness were -0.26, -0.29, and -0.21 ml⋅kg-1⋅beat-1 in women and -0.27, -0.31, and -0.19 ml⋅kg-1⋅beat-1 in men. Adjustment for adiposity and physical activity attenuated the RHR-to-fitness relationship by 10% and 50%, respectively. Longitudinally, a 1-bpm increase in supine RHR was associated with a 0.23 ml⋅min-1⋅kg-1 decrease in fitness. During the pandemic, RHR increased in those with low pre-pandemic fitness but was stable in others. CONCLUSIONS: RHR is a valid population-level biomarker of cardiorespiratory fitness. Physical activity and adiposity attenuate the relationship between RHR and fitness.

Descriptive Epidemiology of Cardiorespiratory Fitness in UK Adults: The Fenland Study.

INTRODUCTION: Cardiorespiratory fitness (CRF) is rarely measured in population studies. Most studies of CRF do not examine differences by population subgroups or seasonal trends. We examined how estimated CRF levels vary by anthropometric, sociodemographic, and behavioral characteristics in a population-based cohort of UK adults (the Fenland Study). METHODS: We used a validated submaximal exercise test to obtain CRF estimates (CRF estimated ) in 5976 women and 5316 men, residing in the East of England. CRF estimated was defined as estimated maximal oxygen consumption per kilogram total body mass (V̇O 2 max tbm ) and fat-free mass (V̇O 2 max ffm ). Descriptive statistics were computed across anthropometric and sociodemographic characteristics, and across the year. Progressive multivariable analyses were performed to examine associations with physical activity energy expenditure (PAEE) and body mass index (BMI). RESULTS: Mean ± SD V̇O 2 max tbm was lower in women (35.2 ± 7.5 mL·min -1 ·kg -1 ) than men (41.7 ± 7.3 mL·min -1 ·kg -1 ) but V̇O 2 max ffm was similar (women: 59.2 ± 11.6 mL·min -1 ·kg -1 ; men: 62.0 ± 10.3 mL·min -1 ·kg -1 ). CRF estimated was inversely associated with age but not after adjustment for PAEE. People in more physically demanding jobs were fitter compared with those in sedentary jobs, but this association was attenuated in women and reversed in men after adjustment for total PAEE. Physical activity energy expenditure and BMI were positively associated with CRF estimated at all levels of adjustment when expressed relative to fat-free mass. CRF estimated was 4% higher in summer than in winter among women, but did not differ by season among men. CONCLUSIONS: CRF estimated was inversely associated with age but less steeply than anticipated, suggesting older generations are comparatively fitter than younger generations. Physical activity energy expenditure and BMI were stronger determinants of the variance in CRF estimated than other characteristic including age. This emphasizes the importance of modifiable physical activity behaviors in public health interventions.

Quantifying the Relationship Between Physical Activity Energy Expenditure and Incident Type 2 Diabetes: A Prospective Cohort Study of Device-Measured Activity in 90,096 Adults.

OBJECTIVE: To investigate the association between accelerometer-derived physical activity energy expenditure (PAEE) and incident type 2 diabetes (T2D) in a cohort of middle-aged adults and within subgroups. RESEARCH DESIGN AND METHODS: Data were from 90,096 UK Biobank participants without prevalent diabetes (mean 62 years of age; 57% women) who wore a wrist accelerometer for 7 days. PAEE was derived from wrist acceleration using a population-specific method validated against doubly labeled water. Logistic regressions were used to assess associations between PAEE, its underlying intensity, and incident T2D, ascertained using hospital episode and mortality data up to November 2020. Models were progressively adjusted for demographic, lifestyle factors, and BMI. RESULTS: The association between PAEE and T2D was approximately linear (n = 2,018 events). We observed 19% (95% CI 17-21) lower odds of T2D per 5 kJ · kg-1 · day-1 in PAEE without adjustment for BMI and 11% (9-13) with BMI adjustment. The association was stronger in men than women and weaker in those with obesity and higher genetic susceptibility to obesity. There was no evidence of effect modification by genetic susceptibility to T2D or insulin resistance. For a given level of PAEE, odds of T2D were lower among those engaging in more moderate-to-vigorous activity. CONCLUSIONS: There was a strong linear relationship between PAEE and incident T2D. A difference in PAEE equivalent to an additional daily 20-min brisk walk was associated with 19% lower odds of T2D. The association was broadly similar across population subgroups, supporting physical activity for diabetes prevention in the whole population.

Longitudinal cardio-respiratory fitness prediction through wearables in free-living environments.

Cardiorespiratory fitness is an established predictor of metabolic disease and mortality. Fitness is directly measured as maximal oxygen consumption (VO2max), or indirectly assessed using heart rate responses to standard exercise tests. However, such testing is costly and burdensome because it requires specialized equipment such as treadmills and oxygen masks, limiting its utility. Modern wearables capture dynamic real-world data which could improve fitness prediction. In this work, we design algorithms and models that convert raw wearable sensor data into cardiorespiratory fitness estimates. We validate these estimates' ability to capture fitness profiles in free-living conditions using the Fenland Study (N=11,059), along with its longitudinal cohort (N = 2675), and a third external cohort using the UK Biobank Validation Study (N = 181) who underwent maximal VO2max testing, the gold standard measurement of fitness. Our results show that the combination of wearables and other biomarkers as inputs to neural networks yields a strong correlation to ground truth in a holdout sample (r = 0.82, 95CI 0.80-0.83), outperforming other approaches and models and detects fitness change over time (e.g., after 7 years). We also show how the model's latent space can be used for fitness-aware patient subtyping paving the way to scalable interventions and personalized trial recruitment. These results demonstrate the value of wearables for fitness estimation that today can be measured only with laboratory tests.

Cardiorespiratory fitness assessment using risk-stratified exercise testing and dose-response relationships with disease outcomes.

Cardiorespiratory fitness (CRF) is associated with mortality and cardiovascular disease, but assessing CRF in the population is challenging. Here we develop and validate a novel framework to estimate CRF (as maximal oxygen consumption, VO2max) from heart rate response to low-risk personalised exercise tests. We apply the method to examine associations between CRF and health outcomes in the UK Biobank study, one of the world's largest and most inclusive studies of CRF, showing that risk of all-cause mortality is 8% lower (95%CI 5-11%, 2670 deaths among 79,981 participants) and cardiovascular mortality is 9% lower (95%CI 4-14%, 854 deaths) per 1-metabolic equivalent difference in CRF. Associations obtained with the novel validated CRF estimation method are stronger than those obtained using previous methodology, suggesting previous methods may have underestimated the importance of fitness for human health.

Estimating physical activity from self-reported behaviours in large-scale population studies using network harmonisation: findings from UK Biobank and associations with disease outcomes.

BACKGROUND: UK Biobank is a large prospective cohort study containing accelerometer-based physical activity data with strong validity collected from 100,000 participants approximately 5 years after baseline. In contrast, the main cohort has multiple self-reported physical behaviours from > 500,000 participants with longer follow-up time, offering several epidemiological advantages. However, questionnaire methods typically suffer from greater measurement error, and at present there is no tested method for combining these diverse self-reported data to more comprehensively assess the overall dose of physical activity. This study aimed to use the accelerometry sub-cohort to calibrate the self-reported behavioural variables to produce a harmonised estimate of physical activity energy expenditure, and subsequently examine its reliability, validity, and associations with disease outcomes. METHODS: We calibrated 14 self-reported behavioural variables from the UK Biobank main cohort using the wrist accelerometry sub-cohort (n = 93,425), and used published equations to estimate physical activity energy expenditure (PAEESR). For comparison, we estimated physical activity based on the scoring criteria of the International Physical Activity Questionnaire, and by summing variables for occupational and leisure-time physical activity with no calibration. Test-retest reliability was assessed using data from the UK Biobank repeat assessment (n = 18,905) collected a mean of 4.3 years after baseline. Validity was assessed in an independent validation study (n = 98) with estimates based on doubly labelled water (PAEEDLW). In the main UK Biobank cohort (n = 374,352), Cox regression was used to estimate associations between PAEESR and fatal and non-fatal outcomes including all-cause, cardiovascular diseases, respiratory diseases, and cancers. RESULTS: PAEESR explained 27% variance in gold-standard PAEEDLW estimates, with no mean bias. However, error was strongly correlated with PAEEDLW (r = -.98; p < 0.001), and PAEESR had narrower range than the criterion. Test-retest reliability (Λ = .67) and relative validity (Spearman = .52) of PAEESR outperformed two common approaches for processing self-report data with no calibration. Predictive validity was demonstrated by associations with morbidity and mortality, e.g. 14% (95%CI: 11-17%) lower mortality for individuals meeting lower physical activity guidelines. CONCLUSIONS: The PAEESR variable has good reliability and validity for ranking individuals, with no mean bias but correlated error at individual-level. PAEESR outperformed uncalibrated estimates and showed stronger inverse associations with disease outcomes.

Validation of Submaximal Step Tests and the 6-Min Walk Test for Predicting Maximal Oxygen Consumption in Young and Healthy Participants.

Background: This study aimed to test the validity of three different submaximal tests (i.e., 3-min step test with 20.3-cm step box height (3MST20), 3-min step test with 30-cm step box height (3MST30), and 6-min walk test (6MWT)) in estimating maximal oxygen consumption (VO2max) in young and healthy individuals. Methods: The 3MST20, 3MST30, 6MWT, as well as the cardiopulmonary exercise test (CPET) were performed in 73 participants (37 men and 36 women; mean age: 30.8 ± 9.3 years). All participants visited the clinic three times in a random order for anthropometric measurements, three submaximal tests, and the VO2max test. Multiple linear regression analyses were conducted to construct the VO2max prediction equations for each submaximal test. Results: The prediction equations developed based on multiple regression analyses for each submaximal tests were as follows: 3MST20: VO2max = 86.0 - 10.9 × sex (male = 1, female = 2) - 0.4 × age - 0.1 × weight - 0.1 × heart rate recovery at 30 s (HRR30s); 3MST30: VO2max = 84.5 - 10.2 × sex (male = 1, female = 2) - 0.4 × age - 0.1 × weight - 0.1 × HRR30s; and 6MWT: VO2max = 61.1 - 11.1 × sex (male = 1, female = 2) - 0.4 × age - 0.2 × weight - 0.2 × (distance walked·10-1). The estimated VO2max values based on formulated equations were 37.0 ± 7.9, 37.3 ± 7.6, and 36.9 ± 7.9 mL∙kg-1∙min-1 derived from the 3MST20, 3MST30, and 6MWT, respectively. These estimated VO2max values were not significantly different from the measured VO2max value, 37.3 mL∙kg-1∙min-1. The estimated VO2max based on the 3MST20, 3MST30, and 6MWT results explained 73.4%, 72.2%, and 74.4% of the variances in the measured VO2max (p < 0.001), respectively. Conclusions: The 3MST20, 3MST30, and 6MWT were valid in estimating VO2max in relatively young and healthy Asian individuals.

Association Between Muscle Strength and Modeling Estimates of Muscle Tissue Heterogeneity in Young and Old Adults.

OBJECTIVES: Assessing aging muscle through estimates of muscle heterogeneity may overcome some of the limitations of grayscale analyses. The objectives of this study included determining statistical model parameters that characterize muscle echogenicity and are associated with strength in younger and older participants. METHODS: Thirty-three community-dwelling participants were assigned to younger and older groups. Quantitative B-mode ultrasound scanning of the rectus femoris and isometric grip strength testing were completed. Shape or dispersion parameters from negative binomial distribution, Nakagami, gamma, and gamma mixture models were fitted to the grayscale histograms. RESULTS: The mean ages ± SDs of the younger and older groups were 24.0 ± 2.3 and 65.1 ± 6.5 years, respectively. Statistical model shape and dispersion parameters for the grayscale histograms significantly differed between the younger and older participants (P = .002-.006). Among all of the statistical models considered, the gamma mixture model showed the best fit with the grayscale histograms (χ2 goodness of fit = 62), whereas the Nakagami distribution displayed the poorest fit (χ2 goodness of fit = 2595). Grayscale values were significantly associated with peak grip strength force in younger adult participants (R2 = 0.36; P < .008). However, the negative binomial dispersion parameter k (adjusted R2 = 0.70; P < .001) and gamma shape parameter α (adjusted R2 = 0.68; P < .01) showed the highest associations with peak grip strength force in older adult participants. CONCLUSIONS: The negative binomial dispersion parameter k and the gamma shape parameter α have clinical relevance for the assessment of age-related muscle changes. Statistical models of muscle heterogeneity may characterize the association between muscle tissue composition estimates and strength better than grayscale measures in samples of community-dwelling older adults.

Eccentric Exercise Program Design: A Periodization Model for Rehabilitation Applications.

The applied use of eccentric muscle actions for physical rehabilitation may utilize the framework of periodization. This approach may facilitate the safe introduction of eccentric exercise and appropriate management of the workload progression. The purpose of this data-driven Hypothesis and Theory paper is to present a periodization model for isokinetic eccentric strengthening of older adults in an outpatient rehabilitation setting. Exemplar and group data are used to describe the initial eccentric exercise prescription, structured familiarization procedures, workload progression algorithm, and feasibility of the exercise regimen. Twenty-four men (61.8 ± 6.3 years of age) completed a 12-week isokinetic eccentric strengthening regimen involving the knee extensors. Feasibility and safety of the regimen was evaluated using serial visual analog scale (VAS, 0-10) values for self-reported pain, and examining changes in the magnitude of mean eccentric power as a function of movement velocity. Motor learning associated with the familiarization sessions was characterized through torque-time curve analysis. Total work was analyzed to identify relative training plateaus or diminished exercise capacity during the progressive phase of the macrocycle. Variability in the mean repetition interval decreased from 68 to 12% during the familiarization phase of the macrocycle. The mean VAS values were 2.9 ± 2.7 at the start of the regimen and 2.6 ± 2.9 following 12 weeks of eccentric strength training. During the progressive phase of the macrocycle, exercise workload increased from 70% of the estimated eccentric peak torque to 141% and total work increased by 185% during this training phase. The slope of the total work performed across the progressive phase of the macrocycle ranged from -5.5 to 29.6, with the lowest slope values occurring during microcycles 8 and 11. Also, mean power generation increased by 25% when eccentric isokinetic velocity increased from 60 to 90° s-1 while maintaining the same workload target. The periodization model used in this study for eccentric exercise familiarization and workload progression was feasible and safe to implement within an outpatient rehabilitation setting. Cyclic implementation of higher eccentric movement velocities, and the addition of active recovery periods, are featured in the proposed theoretical periodization model for isokinetic eccentric strengthening.

Short-Term Adaptation of Joint Position Sense Occurs during and after Sustained Vibration of Antagonistic Muscle Pairs.

Proprioception is critical for the control of many goal-directed activities of daily living. While contributions from skin and joint receptors exist, the muscle spindle is thought to play an important role in allowing accurate judgments of limb position and movement to occur. The discharges elicited from muscle spindles can be degraded by simultaneous agonist-antagonist tendon vibration, causing proprioception to be distorted. Despite this, changes in limb perception that may result from sensory adaptation to this stimulus remain misunderstood. The purpose of this study was, therefore, to investigate short-term proprioceptive adaptation resulting from vibration of antagonistic muscle pairs. We measured elbow joint position sense in 21 healthy young adults while 80 Hz vibration was applied simultaneously to the distal tendons of the elbow flexor and extensor muscles. Matching errors were then analyzed during early and late adaptation phases to assess short-term adaptation to the vibration stimuli. Participants committed significant undershoot errors during the early adaptation phase, but were comparable to baseline measurements during the late adaptation phase. When we removed the vibration stimuli and conducted a second joint position matching task, matching variability increased significantly, and participants committed overshoot errors. These results bring into question the efficacy of simultaneous agonist-antagonist tendon vibration to degrade proprioceptive acuity.

Stride interval dynamics are altered when two individuals walk side by side.

The purpose of this study was to examine the effects of interpersonal synchronization of stepping on stride interval dynamics during over-ground walking. Twenty-seven footswitch instrumented subjects walked under three conditions: independent (SOLO), alongside a partner (PAIRED), and side by side with intentional synchronization (FORCED). A subset of subjects also synchronized stepping to a metronome (MET). Stride time power spectral density and detrended fluctuation analysis revealed that the rate of autocorrelation decay in stride time was similar for both the SOLO and PAIRED conditions, but was significantly reduced during the FORCED and MET conditions (p=0.03 & 0.002). Stride time variability was also significantly increased for the FORCED and MET conditions (p<0.001). These data suggest that forced synchronization of stepping results in altered stride interval dynamics, likely through increased active control by the CNS. Passive side by side stepping, where synchronization is subconscious, does not appreciably alter stepping in this manner.

Gross and fine anatomy of the respiratory vasculature of the mudskipper, Periophthalmodon schlosseri (Gobiidae: Oxudercinae).

To illustrate vascular modification accompanying transition from aquatic to amphibious life in gobies, we investigated the respiratory vasculatures of the gills and the bucco-opercular cavities in one of the most terrestrially-adapted mudskippers, Periophthalmodon schlosseri, using the corrosion casting technique. The vascular system of Pn. schlosseri retains the typical fish configuration with a serial connection of the gills and the systemic circuits, suggesting a lack of separation of O(2)-poor systemic venous blood and O(2)-rich effluent blood from the air-breathing surfaces. The gills appear to play a limited role in gas exchange, as evidenced from the sparsely-spaced short filaments and the modification of secondary lamellar vasculature into five to eight parallel channels that are larger than red blood cell size, unlike the extensive sinusoidal system seen in purely water-breathing fishes. In contrast, the epithelia of the bucco-opercular chamber, branchial arches, and leading edge of the filaments are extensively laden with capillaries having a short (<10 µm) diffusion distance, which strongly demonstrate the principal respiratory function of these surfaces. These capillaries form spiral coils of three to five turns as they approach the epithelial surface. The respiratory capillaries of the bucco-opercular chamber are supplied by efferent blood from the gills and drained by the systemic venous pathway. We also compared the degree of capillarization in the bucco-opercular epithelia of Pn. schlosseri with that of the three related intertidal-burrowing gobies (aquatic, non-air-breathing Acanthogobius hasta; aquatic, facultative air-breathing Odontamblyopus lacepedii; amphibious air-breathing Periophthalmus modestus) through histological analysis. The comparison revealed a clear trend of wider distribution of denser capillary networks in these epithelia with increasing reliance on air breathing, consistent with the highest aerial respiratory capacity of Pn. schlosseri among the four species.

Air breathing of aquatic burrow-dwelling eel goby, Odontamblyopus lacepedii (Gobiidae: Amblyopinae).

Odontamblyopus lacepedii is an eel goby that inhabits both coastal waters and intertidal zones in East Asia, including Japan. The fish excavates burrows in mudflats but, unlike the sympatric amphibious mudskippers, it does not emerge but stays in the burrows filled with hypoxic water during low tide. Endoscopic observations of the field burrows demonstrated that the fish breathed air in the burrow opening; air breathing commenced 1.3 h following burrow emersion, when water P(O2) was approximately 2.8 kPa, with an air-breathing frequency (f(AB)) of 7.3+/-2.9 breaths h(-1) (mean +/- s.d., N=5). Laboratory experiments revealed that the fish is a facultative air breather. It never breathed air in normoxic water (P(O2)=20.7 kPa) but started bimodal respiration when water P(O2) was reduced to 1.0-3.1 kPa. The fish held air inside the mouth and probably used the gills as gas-exchange surfaces since no rich vascularization occurred in the mouth linings. As is known for other air-breathing fishes, f(AB) increased with decreasing water P(O2). Both buccal gas volume (V(B)) and inspired volume (V(I)) were significantly correlated with body mass (M(b)). At a given M(b), V(I) was nearly always equal to V(B), implying almost complete buccal gas renewal in every breathing cycle. A temporal reduction in expired volume (V(E)) was probably due to a low aerial gas exchange ratio (CO2) elimination/O2 uptake). Air breathing appears to have evolved in O. lacepedii as an adaptation to aquatic hypoxia in the burrows. The acquisition of the novel respiratory capacity enables this species to stay in the burrows during low tide and extends the resident time in the mudflat, thereby increasing its chances of tapping the rich resources of the area.

Movimientos Sociales en Bolivia y sus valores socio-religiosos: Desafío para la Iglesia

Contiene: Descripción y análisis sobre los movimientos sociales hoy en Bolivia - Los cocaleros: un nuevo movimiento social que emerge en la historia de Bolivia y sus valores socio-religiosos - Vida, soberanía, tierra y coca: valores socioreligiosos vitales para el pueblo de Dios - La Iglesia en defensa de la vida, soberanía, tierra y coca: desafíos pastorales.