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PubMed2006

Central versus peripheral cardiovascular limitation to exercise: the role of two-modality testing.

BACKGROUND: Uncertainty arises when physiological findings indicate a cardiovascular limitation but the limiting constituents within the cardiovascular system cannot be identified. OBJECTIVES: It was the aim of this study to investigate the value of two-modality exercise testing to assess effort intolerance when the cause remains obscure despite standard exercise testing. METHODS: A second modality maximal exercise test to fatigue, using either upper extremity or supine exercise, was performed following a nonconclusive standard sitting ergometry. Six patients (4 males) with a mean age of 56 +/- 22 years with severe exercise intolerance were enrolled in the study. RESULTS: In 4 of the patients, arm exercise capacity exceeded leg capacity, indicating peripheral limitation. In 1 of these patients, hemoglobin saturation decreased markedly only during sitting exercise while it remained normal during arm exercise, indicating a unique, iatrogenic abnormality. In another patient, supine leg exercise capacity exceeded sitting capacity, indicating peripheral venous limitation, and in an additional patient, leg capacity exceeded arm capacity pointing towards a central abnormality. In all 6 patients, the second modality test highlighted the correct diagnosis. CONCLUSIONS: Arm exercise that is added to a standard leg exercise may distinguish between central circulatory and peripheral vascular lower extremity limitation. Supine posture augments venous return to the heart and is useful when preload may be limiting. These modes of exercise may be added to a standard sitting or upright test in order to differentiate between central cardiovascular versus peripheral vascular (arterial or venous) causes of exercise limitation.

Adolescent↗
PubMed2002

The influence of limit cycle topology on the phase resetting curve.

Understanding the phenomenology of phase resetting is an essential step toward developing a formalism for the analysis of circuits composed of bursting neurons that receive multiple, and sometimes overlapping, inputs. If we are to use phase-resetting methods to analyze these circuits, we can either generate phase-resetting curves (PRCs) for all possible inputs and combinations of inputs, or we can develop an understanding of how to construct PRCs for arbitrary perturbations of a given neuron. The latter strategy is the goal of this study. We present a geometrical derivation of phase resetting of neural limit cycle oscillators in response to short current pulses. A geometrical phase is defined as the distance traveled along the limit cycle in the appropriate phase space. The perturbations in current are treated as displacements in the direction corresponding to membrane voltage. We show that for type I oscillators, the direction of a perturbation in current is nearly tangent to the limit cycle; hence, the projection of the displacement in voltage onto the limit cycle is sufficient to give the geometrical phase resetting. In order to obtain the phase resetting in terms of elapsed time or temporal phase, a mapping between geometrical and temporal phase is obtained empirically and used to make the conversion. This mapping is shown to be an invariant of the dynamics. Perturbations in current applied to type II oscillators produce significant normal displacements from the limit cycle, so the difference in angular velocity at displaced points compared to the angular velocity on the limit cycle must be taken into account. Empirical attempts to correct for differences in angular velocity (amplitude versus phase effects in terms of a circular coordinate system) during relaxation back to the limit cycle achieved some success in the construction of phase-resetting curves for type II model oscillators. The ultimate goal of this work is the extension of these techniques to biological circuits comprising type II neural oscillators, which appear frequently in identified central pattern-generating circuits.

Models, Neurological↗
PubMed2000

Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease.

We investigated the relationship between the reversibility of airflow limitation, the concentration of nitric oxide (NO) in exhaled air, and the inflammatory cells in the sputum of patients with stable chronic obstructive pulmonary disease (COPD). We examined nine normal healthy control subjects and 20 nonatopic patients with COPD. Ten patients had no reversibility of airflow limitation (increase in FEV(1) of < 12% and < 200 ml after 200 microg of inhaled salbutamol), and 10 patients had partial reversibility of airflow limitation (increase in FEV(1) of < 12% but > 200 ml after 200 microg of inhaled salbutamol). Exhaled NO levels were higher in COPD patients with partial reversibility of airflow limitation than in those with no reversibility of airflow limitation (median 24 [interquartile range 15.3 to 32] ppb versus 8.9 [4.6 to 14.7] ppb; p < 0.01). Compared with healthy control subjects, only COPD patients with partial reversibility of airflow limitation had increased concentrations of sputum eosinophils. We conclude that, in patients with stable COPD, even a partial bronchodilator response to inhaled salbutamol is associated with increased exhaled NO and sputum eosinophilia, suggesting that these patients may have a different response to treatment than do those without reversible airflow limitation.

Administration, Inhalation↗
PubMed2002

Infants with flow limitation at 4 weeks: outcome at 6 and 11 years.

Within a longitudinal study of lung function in 243 infants, we identified a group of 23 individuals with flow limitation in tidal expiration. In infancy, flow-limited children have reduced lung function and increased airway responsiveness (AR), and at 2 years of age they are diagnosed with asthma more frequently. We hypothesized that these observations would persist throughout childhood. Data from ages 3 to 11 years were analyzed. Only at 4 years of age did the flow-limited group have increased wheeze compared with other cohort members (odds ratio, 4.25; 95% confidence interval [CI], 1.11 to 16.2; p = 0.04; n = 114). At 6 years of age, 117 cohort members were seen. The flow-limited group (n = 14) had greater AR (p = 0.009) and reduced mean FEV(1) (131 ml; 95% CI, 16 to 246; p = 0.03) and FEF(25-75) (0.28 L/second; 95% CI, 0.05 to 0.52; p = 0.02). At 11 years of age, 183 children were seen and the flow-limited group (n = 18) had greater AR (p = 0.02) and a trend toward reduced mean FEF(25-75) (0.24 L/second; 95% CI, -0.02 to 0.49; p = 0.08). Atopy and parental asthma were not increased in the flow-limited group. We suggest that the physiologic abnormality that causes flow limitation in early infancy may identify an at-risk group, different from asthma, who have reduced lung function and increased airway responsiveness in later life.

Child↗
PubMed2003

Acceleration of key reactions as a strategy to elucidate the rate-limiting chemistry underlying phototransduction inactivation.

PURPOSE: A reconstituted system was used to establish a strategy to determine the rate-limiting chemistry responsible for recovery of the dim-flash response in rod photoreceptors. METHODS: A general approach for identifying the rate-limiting step in a series of reactions is to evaluate the consequences of accelerating each step separately, while monitoring the rate of formation of the end product of the series. This strategy was applied to the reactions involved in quenching phototransduction in bovine rod outer segment (bROS) homogenates. The decay of photoactivated rhodopsin (R*) and inactivation of transducin by guanosine triphosphate (GTP) hydrolysis are the leading candidates for limiting the rate of phototransduction turn-off. These reactions were accelerated separately and together by adding hydroxylamine and/or the regulator of G-protein signaling-9 catalytic domain (RGS9d) while monitoring phosphodiesterase (PDE) activity triggered by a pulse of light in bROS homogenates. RESULTS: PDE activity in bROS homogenates triggered by a flash of light returned to its dark value with a rate constant of 0.087 +/- 0.002 seconds in this system. The rate of PDE recovery increased to 0.11 +/- 0.004 seconds when R* decay was accelerated with 10 to 50 mM hydroxylamine, suggesting that R* inactivation limits the rate of phototransduction turn-off under these conditions. Adding both hydroxylamine and RGS9d, a factor that accelerates transducin inactivation, increased the rate of PDE decay even further. RGS9d had no effect on PDE recovery kinetics unless quenching of R* was also accelerated. CONCLUSIONS: Under in vitro conditions in bROS homogenates, the quenching of R* normally limits the rate of phototransduction shut-off. If R* decay is accelerated, inactivation of transducin by GTP hydrolysis becomes rate limiting. This study offers a general approach that could be used to investigate the rate-limiting chemistry of phototransduction turn-off in vivo.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Therapeutic limit setting and six-month outcomes in a Veterans Affairs assertive community treatment program.

OBJECTIVE: This study examined the relationship of limit-setting interventions and six-month outcomes in assertive community treatment. METHODS: Case managers from 40 Veterans Affairs assertive community treatment teams at 40 different sites documented their use of 25 limit-setting activities with 1564 clients during the first six months of treatment. Five scales were constructed representing different types of limit-setting activities: withholding certain types of assistance until the client curtailed certain behaviors; behavioral contracting in which specific goals were identified and linked to reinforcers if the goals were achieved; invocation of external authorities, such as a probation officer; seeking a declaration of incompetence to manage funds or initiation of a request for a payee; and forced hospitalization through civil commitment. Structured interviews conducted at baseline and six months documented changes in clinical status and community adjustment. Multiple regression analysis was used to examine the relationship between limit-setting interventions and outcomes at both the level of the individual client and at the level of the team, adjusting for potentially confounding baseline client characteristics. RESULTS: All five measures of specific limit-setting activities were associated with poorer outcomes on four to six of the eight outcome measures. The site-level comparison of outcomes showed more violent behavior at sites that made more extensive use of these interventions but also greater employment. CONCLUSIONS: After the analysis controlled for potentially confounding factors, clients exposed to limit-setting interventions had poorer outcomes than others on many measures, suggesting that within the limits of a nonexperimental study, such interventions do not appear to prevent adverse outcomes.

Case Management↗
PubMed2006

Expiratory flow limitation detected by forced oscillation and negative expiratory pressure.

The within-breath change in reactance (Delta(rs)) measured by forced oscillation technique (FOT) at 5 Hz reliably detects expiratory flow limitation in chronic obstructive pulmonary disease (COPD). The present study compared this approach to the standard negative expiratory pressure (NEP) method. In total, 21 COPD patients were studied by applying both techniques to the same breath and in 15 patients the measurements were repeated after bronchodilator. For each patient and condition five NEP tests were performed and independently scored by three operators unaware of the FOT results. In 180 tests, FOT classified 53.3% as flow limited. On average, the operators scored 27.6% of tests flow limited and 47.6% non-flow limited, but could not score 24.8%. The methods disagreed in 7.9% of cases; in 78% of these the NEP scores differed between operators. Bronchodilation reduced NEP and DeltaX(rs) scores, with only the latter achieving significance. Averaging the operators' NEP scores, a threshold between 24.6-30.8% of tidal volume being flow limited by NEP produced 94% agreement between methods. In conclusion, when negative expiratory pressure and forced oscillation technique were both available they showed good agreement. As forced oscillation technique is automatic and can measure multiple breaths over long periods, it is suitable for monitoring expiratory flow limitation continuously and identifying patients' breathing close to the onset of expiratory flow limitation, where intermittent sampling may be unrepresentative.

Forced Expiratory Flow Rates↗
PubMed2006

The Single Item Literacy Screener: evaluation of a brief instrument to identify limited reading ability.

BACKGROUND: Reading skills are important for accessing health information, using health care services, managing one's health and achieving desirable health outcomes. Our objective was to assess the diagnostic accuracy of the Single Item Literacy Screener (SILS) to identify limited reading ability, one component of health literacy, as measured by the S-TOFHLA. METHODS: Cross-sectional interview with 999 adults with diabetes residing in Vermont and bordering states. Participants were randomly recruited from Primary Care practices in the Vermont Diabetes Information System June 2003-December 2004. The main outcome was limited reading ability. The primary predictor was the SILS. RESULTS: Of the 999 persons screened, 169 (17%) had limited reading ability. The sensitivity of the SILS in detecting limited reading ability was 54% [95% CI: 47%, 61%] and the specificity was 83% [95% CI: 81%, 86%] with an area under the Receiver Operating Characteristics Curve (ROC) of 0.73 [95% CI: 0.69, 0.78]. Seven hundred seventy (77%) screened negative on the SILS and 692 of these subjects had adequate reading skills (negative predictive value = 0.90 [95% CI: 0.88, 0.92]). Of the 229 who scored positive on the SILS, 92 had limited reading ability (positive predictive value = 0.4 [95% CI: 0.34, 0.47]). CONCLUSION: The SILS is a simple instrument designed to identify patients with limited reading ability who need help reading health-related materials. The SILS performs moderately well at ruling out limited reading ability in adults and allows providers to target additional assessment of health literacy skills to those most in need. Further study of the use of the SILS in clinical settings and with more diverse populations is warranted.

Adult↗
PubMed2003

Limits to sustained energy intake. VI. Energetics of lactation in laboratory mice at thermoneutrality.

The limits to sustained energy intake are important because of their implications for reproductive output, foraging behaviour and thermoregulatory capabilities. Recent attempts to elucidate the nature of the limits to sustained energy intake have focused on peak lactation, which is the most energetically demanding period for female mammals. The hypothesis that performance of lactating animals is limited peripherally by the capacity of mammary glands to produce milk has received the most attention. However, some empirical data cannot be explained by the peripheral limitation hypothesis. Here, we present a novel hypothesis that the limits to sustained energy intake at peak lactation are imposed by the capacity of the animal to dissipate body heat generated as a by-product of processing food and producing milk. To test the heat dissipation limit hypothesis we challenged reproducing MF1 laboratory mice (N=67) with a reduced potential heat flow between the animal and the environment by exposing them to 30 degrees C (thermoneutral zone). We compared their food intake and reproductive output at peak lactation with animals studied previously at 21 degrees C (N=71) and 8 degrees C (N=15). Mice lactating at 30 degrees C had a significantly lower mean asymptotic food intake (12.4 g day(-1)) than those at 21 degrees C (23.5 g day(-1)) and 8 degrees C (28.6 g day(-1)). On average, mice at 30 degrees C raised significantly fewer (9.8) and smaller (6.1 g) pups than those at 21 degrees C (11.3 pups; 7.0 g per pup) and smaller pups than those at 8 degrees C (9.6 pups; 7.3 g per pup). Consequently, mean litter mass at 30 degrees C (56.0 g) was significantly lower than at 21 degrees C (77.1 g) and at 8 degrees C (68.7 g). The mean rate of litter mass increase at 30 degrees C (2.1 g day(-1)) was also lower than at 21 degrees C (3.1 g day(-1)). The reduced food intake and low reproductive output in mice lactating at 30 degrees C are consistent with the heat dissipation limit hypothesis.

Animals↗
PubMed1985

Malleability of the system in overcoming limitations: functional elements.

Three different views can be found in the literature concerning the classical question in exercise physiology: what limits maximal oxygen uptake in man? Some authors believe that the limitation is the maximal rate of oxygen delivery by the cardiovascular system. Others argue that oxygen uptake is limited by the capillary bed or metabolic capacity of skeletal muscle, and the third line of thought is that no single factor can be found to be directly limiting as all links in the oxygen transport are so closely matched. The stand taken in this paper is that the skeletal muscle of man can be excluded as a limiting factor for maximal oxygen uptake in whole body exercise. It can be shown, by direct measurements, that in sedentary and in trained man maximal perfusion and oxygen utilization of skeletal muscle is so high that if all muscles in the body were engaged in intense exercise, the cardiac pump function would have to be 2-3 fold larger than it is. What happens in whole body exercise is that each muscle group receives only a fraction of the blood it can accommodate. The primary role for a larger capillary network observed in trained muscles is to keep or extend mean transit time. Elevated mitochondrial enzyme activities affect the metabolic response (i.e. lipid oxidation is elevated in trained muscles). However, these adaptations are not necessary for increasing the maximal oxygen uptake of man, as the capacity of the heart is limiting. Improved training techniques (which induce even larger improvements in cardiac pump function) may reveal that pulmonary diffusion capacity is the limiting factor.

Adaptation, Physiological↗
PubMed2001

Limits to sustained energy intake. V. Effect of cold-exposure during lactation in Mus musculus.

We have previously observed that female MF1 mice appeared to reach a limit in their food intake and milk production during late lactation, reaching a plateau between days 13 and 16 of lactation and between litter sizes of 9 and 15. These mice did not increase their food intake when forced to raise more offspring or when manipulated to be concurrently pregnant during late lactation, yet they did eat significantly more food at the peak of their second sequential lactation or when challenged with food of reduced energy content. These data suggest that apparent limits on sustained energy intake in this strain may not reflect central limitations but rather peripheral constraints at the mammary glands. In this study, we aimed to determine whether these were indeed limits by increasing the demands on the females during late lactation by cold-exposure (8 degrees C). Females responded to this manipulation by significantly increasing their food intake (F1,73=77.53, P<0.001) above that of lactating females kept in warmer conditions (21 degrees C). In addition, there was a significant reduction in the number of pups raised in the cold (t=2.36, d.f.=18, P=0.03), with the majority of the mortality occurring within the first 2 days of cold-exposure. The mean mass of the pups raised in the cold was significantly lower (F1,74=13.8, P<0.001) than that of those raised in the warm. Despite the cold-exposure and the increased food intake, there was no difference in the resting metabolic rates of the two groups of mothers or in the lengths of their small intestine. The greater food intake of lactating mice during cold-exposure supported our previous observations that they were capable of eating more food than the previously suggested limit of 23.1 g x day(-1). However, the milk energy output of females in the cold was also significantly higher than in the warm (F1,15=11.99, P=0.003), indicating that the asymptotic food intake of females in the warm was not mediated by limitations in their milk production. Sustained energy intake in these mice does not appear to be centrally or peripherally limited. Rather, the mice may restrain their use of energy during their first lactation because of life-history consequences for future reproductive attempts.

Acclimatization↗
PubMed2005

A review of troponin assay performance in Wales: can the same (method-dependent) decision limits be used in different sites?

An audit of troponin measurement protocols in use in Wales showed significant variations in practice with no consensus on analytical methods, or in the selection of a decision limit for the diagnosis of myocardial damage. Peer review data on assay imprecision at concentrations approaching the analytical limit of detection are lacking. The objective of the study was to establish clinically relevant precision profiles for the troponin methods used throughout Wales, which could be used to develop a standardized approach to the selection of a decision limit. A series of five pools of human serum spiked with troponin I-T complex were prepared and stored at -70 degrees C until dispatch. Five sets of each pool were dispatched to all Welsh laboratories and stored at -20 degrees C until analysis. The analysis protocol consisted of two replicates of each pool per batch, and two batches per day for five days (n=20). All the laboratories performed all the measurements in the same week. The lowest concentration providing a 10% coefficient of variation (CV) was 0.02 microg/L for the Roche method and 0.11 microg/L for the Beckman AccuTnI. The lowest concentrations that could be distinguishable from the 99th percentile reference limit were 0.02 microg/L for the Roche method and 0.07 microg/L for the Beckman AccuTnI. Current methods do not achieve the 10% CV at the 99th percentile reference limit proposed by the European Society of Cardiology. Use of the lowest concentration that can be reliably distinguished from the 99th percentile reference limit offers a novel alternative decision limit, which provides a slightly lower concentration than at the 10% CV but maintaining confidence in the assay that false-positive rates will be minimized.

Chemistry, Clinical↗
PubMed2004

Epidemiologic evaluation of measurement data in the presence of detection limits.

Quantitative measurements of environmental factors greatly improve the quality of epidemiologic studies but can pose challenges because of the presence of upper or lower detection limits or interfering compounds, which do not allow for precise measured values. We consider the regression of an environmental measurement (dependent variable) on several covariates (independent variables). Various strategies are commonly employed to impute values for interval-measured data, including assignment of one-half the detection limit to nondetected values or of "fill-in" values randomly selected from an appropriate distribution. On the basis of a limited simulation study, we found that the former approach can be biased unless the percentage of measurements below detection limits is small (5-10%). The fill-in approach generally produces unbiased parameter estimates but may produce biased variance estimates and thereby distort inference when 30% or more of the data are below detection limits. Truncated data methods (e.g., Tobit regression) and multiple imputation offer two unbiased approaches for analyzing measurement data with detection limits. If interest resides solely on regression parameters, then Tobit regression can be used. If individualized values for measurements below detection limits are needed for additional analysis, such as relative risk regression or graphical display, then multiple imputation produces unbiased estimates and nominal confidence intervals unless the proportion of missing data is extreme. We illustrate various approaches using measurements of pesticide residues in carpet dust in control subjects from a case-control study of non-Hodgkin lymphoma.

Bias↗
PubMed1998

Interpretive algorithms for the symptom-limited exercise test: assessing dyspnea in Persian Gulf war veterans.

Interpretation of symptom-limited exercise testing requires analysis of a large body of simultaneously recorded cardiopulmonary data. Karlman Wasserman has recommended an algorithmic approach to interpretation (WA) that leads to a dichotomous choice between pulmonary and cardiovascular impairment. An alternative algorithm published by William Eschenbacher (EA) provides for concurrent assessment of cardiovascular and pulmonary exercise impairment. We analyzed a group of 29 individuals referred to the Pulmonary Physiology Laboratory at the Washington Veterans Affairs Medical Center for evaluation of dyspnea following service in the Persian Gulf War to assess the concordance of the two algorithms in determining the cause of dyspnea and exercise impairment in these individuals. They each performed a progressive, ramped, symptom-limited exercise test on a bike for a minimum of 6 min. Exercise measurements were analyzed by both interpretive algorithms. Concordance was found in 28% of tests. The greatest discordance occurred in identifying pulmonary limitation. Eleven had pulmonary limitation by EA; of these, WA found 1 to have pulmonary limitation, 5 to be normal, 4 indeterminate, and 1 musculoskeletal limitation. Of the 11 with pulmonary limitation by EA, but not by WA, 5 had abnormal resting pulmonary function measurements. Analysis of the differences between these two interpretive approaches is given. The EA algorithm may be more sensitive for detecting exercise impairment of pulmonary origin, but its specificity remains to be determined.

Adult↗
PubMed2005

Exercise outcomes after pulmonary rehabilitation depend on the initial mechanism of exercise limitation among non-oxygen-dependent COPD patients.

STUDY OBJECTIVES: Pulmonary rehabilitation (PR) that includes exercise training can improve exercise tolerance and quality of life for patients with COPD. However, the degree of benefit from PR is variable. We hypothesized that the exercise response to PR varies depending on the initial factors that limit exercise. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We retrospectively analyzed the change in exercise capacity after PR in 290 nonhypoxemic patients with COPD. We classified patients into the following subgroups based on the primary limitation seen on initial exercise testing: (1) ventilatory-limited (VL); (2) cardiovascular-limited (CVL); (3) mixed ventilatory/cardiovascular-limited (VLCVL); and (4) non-cardiopulmonary-limited (NL). We compared outcomes among subgroups. RESULTS: In the entire study population, PR led to increased timed walk distance (30.3%; p < 0.0001) and maximal oxygen consumption (VO2max) [84.8 mL/min; p < 0.0001]. Stepwise multiple regression selected age, ventilatory reserve at peak exercise, and exercise arterial oxygen pressure as individual predictors of improvement in VO2max. VO2max increased in the VL subgroup (30.4 mL/min; p = 0.008), the CVL subgroup (109.0 mL/min; p < 0.0001), the mixed VLCVL subgroup (61.3 mL/min; p < 0.0001), and NL subgroups (110.5 L/min; p < 0.0001). The improvement in VO2max was greater in the CVL subgroup than in the VL subgroup (p < 0.0001). Timed walk distance improved to a similar degree in all subgroups (26 to 36%). CONCLUSIONS: Patients with nonventilatory exercise limitations experience the greatest increase in VO2max after PR. However, even patients with severe ventilatory limitation can improve exercise tolerance with PR.

Aged↗
PubMed1993

A new look at the limits of detection (LD), quantification (LQ) and power of definition (PD)

The relationship between the concentration of the analyte and the imprecision of an analytical method can be displayed by the precision profile in which the coefficient of variation (relative standard deviation) is plotted against the concentration of the analyte. The function of the curve of the profile and its confidence limits can easily be assessed by a computer program developed by W.A. Sadler & M.H. Smith (Clin. Chem. 36 (1990), 1346-1350). For the assessment of limits of detection and of quantification the following procedure is proposed: The lower (and upper) limit of the measuring interval is defined by the point at which an acceptable CV-line intersects the confidence limit. If, in the variance function one sets the concentration to zero, the normal distribution of the random errors of the blank will result. The mean of the next adjacent normal distribution, following the variance formula and overlapping the "zero-distribution" by a defined amount, represents the limit of detection. Within the described measuring interval, or within a fraction of it, one might construct overlapping normal distributions in an analogous manner. Their number represents the "power of definition" (PD) (instead of the "analytical sensitivity"), which also depends on the concentration of the determinand according to the variance function. We tested these hypotheses by a comparison of two methods for the determination of cyclosporin A (ciclosporin, INN). Our results demonstrate that the data of the lower limits of the measuring interval and of the limit of detection agree well with data from the literature obtained in extensive interlaboratory surveys.

Algorithms↗
PubMed2002

Regression-based reference limits for urinary amino acids in a pediatric population.

Age-related variation of the urinary excretion of amino acids has been widely reported. Instead of the conventional reference intervals, continuous reference limits might be a more practical approach during periods of rapid changes such as infancy or childhood. Regression-based reference limits have been produced for the urinary excretion of 23 amino acids analyzed in 148 healthy individuals from 0 to 12 years of age. Urinary excretion was modeled as a function of age by two parametric procedures: the polynomial and the piece-wise linear regression methods. Likewise, age-specific standard deviation was estimated by the regression of the absolute values of the residuals on age. Residual analysis was employed to select the best-fitting model and the 95% reference limits, and their 95% confidence intervals were calculated and plotted against the raw data. The urinary excretion of 19 amino acids decreased rapidly during the first year of life with a further slow decline thereafter. These amino acids fit better the piecewise model. The other four amino acids displayed a steady decrease in the urinary excretion from birth to puberty, and the excretion patterns fit better the quadratic or linear model. Fifteen amino acids showed a significant change in standard deviation with age. Regression-based reference limits differed consistently from conventional limits (<3 years) and narrower confidence intervals were obtained throughout the entire period studied. Avoiding partitioning gave rise to smoothly changing limits. Therefore, such alternative way of presenting amino acid reference limits may facilitate the follow-up of patients with inborn errors of amino acid metabolism.

Age Factors↗
PubMed2002

Determination and evaluation of acceptable force limits in single-digit tasks.

Acceptable limits derived from psychophysical methodologies have been proposed, measured, and employed in a range of applications. There is little existing work, however, on such limits for single-digit exertions and relatively limited evidence on several fundamental issues related to data collection and processing of a sequence of self-regulated exertion levels. An experimental study was conducted using 14 male and 10 female participants (age range 18-31 years) from whom maximal voluntary exertions and maximal acceptable limits (MALs) were obtained using the index finger and thumb. Moderate to high levels of consistency were found for both measures between sessions separated by one day. Single MAL values, determined from a time series of exertions, were equivalent across three divergent processing methods and between values obtained from 5- and 25-min samples. A critical interpretation of these and earlier results supports continued use of acceptable limits but also suggests that they should be used with some caution and not equated with safe limits. This research can be applied toward future development of exertion limits based on perceived acceptability.

Adolescent↗