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PubMed2002

Defining the optimum upper heart rate limit during exercise: a study in pacemaker patients with heart failure.

AIMS: There is no non-invasive method to determine the individual optimum of maximum exercise heart rate. Knowledge of this value is of particular interest in patients with structural heart disease who are prone to tachycardia intolerance. The purpose of this study was to define the optimal maximum heart rate using cardiopulmonary exercise testing and exercise Doppler echocardiography and to compare the results of both approaches. METHODS AND RESULTS: In 49 pacemaker patients with chronotropic incompetence, the optimum upper heart rate limit was determined using cardiopulmonary exercise testing and exercise Doppler echocardiography. The optimum upper rate limit was given by the highest pacing rate which still produced an increase in oxygen consumption, or by that pacing rate which was linked to the lowest value for the Doppler-derived myocardial performance index. In patients with normal left ventricular ejection fraction (>or=55%) the optimum upper rate limit was 86% of age-predicted maximum heart rate, in patients with left ventriuclar dysfunction (ejection fraction <or=45%) it was 75% of the age-predicted maximum rate (P=0.004). The optimum upper rate limit, as defined by cardiopulmonary exercise testing and exercise Doppler echocardiography, were closely correlated (P<0.0001) with a mean deviation of 6+/-6 beats x min(-1). CONCLUSION: Cardiopulmonary exercise testing and exercise Doppler echocardiography are valuable tools which help to determine the optimum upper rate limit in order to avoid excess heart rates in heart failure patients. The application of these methods is not limited to pacemaker patients but may be helpful in therapeutic interventions with chronotropic drugs.

Adult↗
PubMed1981

Limited joint mobility in childhood diabetes mellitus indicates increased risk for microvascular disease.

We detected limited mobility of small and large joints in 92 (30 per cent) of 309 patients with diabetes who were one to 28 years old. Among patients who had had diabetes for more than 4.5 years (the shortest duration at which microvascular complications were noted), 82 of 169 had joint limitation. Forty-one of these 82 also had microvascular complications, but only 10 of the 87 patients without joint limitation had complications. Life-table analysis indicated an 83 per cent risk for microvascular complications after 16 years of diabetes if joint limitation was present, but only a 25 per cent risk if joint limitation was absent. Consequently, limited joint mobility identifies a population exceptionally at risk for the early development of microvascular complications, and intervention to forestall or prevent these complications can now be focused.

Adolescent↗
PubMed2005

Fundamental limits of the dispersion of the two-photon absorption cross section.

We rigorously apply the sum rules to the sum-over-states expression to calculate the fundamental limits of the dispersion of the two-photon absorption cross section. A comparison of the theory with the data suggests that the truncated sum rules in the three-level model give a reasonable fundamental limit. Furthermore, we posit that the two-photon absorption cross section near the limit must have only three dominant states, so by default, the three-level model is appropriate. This ansatz is supported by a rigorous analytical calculation that the resonant term gets smaller as more states are added. We also find that the contributions of the nonexplicitly resonant terms cannot be neglected when analyzing real molecules with many excited states, even near resonance. However, puzzling as it may be, extrapolating an off-resonant result to resonance using only the resonant term of the three-level model is shown to be consistent with the exact result. In addition, the off-resonant approximation is shown to scale logarithmically when compared with the full three-level model. This scaling can be used to simplify the analysis of measurements. We find that existing molecules are still far from the fundamental limit; so, there is room for improvement. But, reaching the fundamental limit would require precise control of the energy-level spacing, independently of the transition dipole moments-a task that does not appear possible using today's synthetic approaches. So, we present alternative methods that can still lead to substantial improvements which only require the control of the transition moment to the first excited state. While it is best to normalize measured two-photon absorption cross sections to the fundamental limits when comparing molecules, we show that simply dividing by the square of the number of electrons per molecule yields a good metric for comparison.

Journal Article↗
PubMed2005

Lessons from Escherichia coli genes similarly regulated in response to nitrogen and sulfur limitation.

We previously characterized nutrient-specific transcriptional changes in Escherichia coli upon limitation of nitrogen (N) or sulfur (S). These global homeostatic responses presumably minimize the slowing of growth under a particular condition. Here, we characterize responses to slow growth per se that are not nutrient-specific. The latter help to coordinate the slowing of growth, and in the case of down-regulated genes, to conserve scarce N or S for other purposes. Three effects were particularly striking. First, although many genes under control of the stationary phase sigma factor RpoS were induced and were apparently required under S-limiting conditions, one or more was inhibitory under N-limiting conditions, or RpoS itself was inhibitory. RpoS was, however, universally required during nutrient downshifts. Second, limitation for N and S greatly decreased expression of genes required for synthesis of flagella and chemotaxis, and the motility of E. coli was decreased. Finally, unlike the response of all other met genes, transcription of metE was decreased under S- and N-limiting conditions. The metE product, a methionine synthase, is one of the most abundant proteins in E. coli grown aerobically in minimal medium. Responses of metE to S and N limitation pointed to an interesting physiological rationale for the regulatory subcircuit controlled by the methionine activator MetR.

Bacterial Proteins↗
PubMed1978

Fluorescence energy transfer in the rapid-diffusion limit.

Energy transfer is enhanced by translational diffusion of the donor and acceptor [Steinberg, I. Z. & Katchalski, E. (1968) J. Chem. Phys. 48, 2404-2410]. The effect of diffusion on energy transfer depends on Dtau(0)/s(2), in which D is the sum of the diffusion coefficients of the donor and acceptor, tau(0) is the lifetime of the donor in the absence of transfer, and s is the mean distance between donors and acceptors. In most previous studies, Dtau(0)/s(2) << 1, corresponding to the static limit. We report here steady-state and kinetic fluorescence experiments showing that Dtau(0)/s(2) >> 1, the rapid-diffusion limit, can be attained by using Tb(3+) chelated to dipicolinate as a long-lived energy donor (tau(0) = 2.2 msec). The concentration of rhodamine B, the energy acceptor, resulting in 50% transfer was 0.67 muM, which is three orders of magnitude less than the concentration giving 50% transfer in the static limit. The dependence of the transfer efficiency on diffusion coefficients varying from 5 x 10(-11) to 1.5 x 10(-4) cm(2)/sec, spanning the range from the static limit to the rapid-diffusion limit, is in excellent agreement with theory. It is evident that energy donors with millisecond or longer excited state lifetimes can be used to probe translational motions in membranes and other assemblies. Energy transfer in the rapid diffusion limit is sensitive to the distance of closest approach (a) of the donor and acceptor. For a Tb.(DPA)(3) chelate trapped inside the aqueous space of a membrane vesicle containing eosin phosphatidylethanolamine, a = 10 A. The transverse location of chromophores in model membranes and biological membranes can be determined by this technique.

Journal Article↗
PubMed2005

Interaction of RNA-binding proteins HuR and AUF1 with the human ATF3 mRNA 3'-untranslated region regulates its amino acid limitation-induced stabilization.

ATF3 expression is induced in cells exposed to a variety of stress conditions, including nutrient limitation. Here we demonstrated that the mechanism by which the ATF3 mRNA content is increased following amino acid limitation of human HepG2 hepatoma cells is mRNA stabilization. Analysis of ATF3 mRNA turnover revealed that the half-life was increased from about 1 h in control cells to greater than 8 h in the histidine-deprived state, demonstrating mRNA stabilization in response to nutrient deprivation. Treatment of HepG2 cells with thapsigargin, which causes endoplasmic reticulum stress, also increased the half-life of ATF3 mRNA. HuR is an RNA-binding protein that regulates both the stability and cytoplasmic/nuclear localization of mRNA species containing AU-rich elements. Another RNA-binding protein, AUF1, regulates target mRNA molecules by enhancing their decay. Amino acid limitation caused a slightly elevated mRNA level for HuR and AUF1 mRNA. The nuclear HuR protein content was unchanged, and AUF1 protein increased slightly after amino acid limitation, whereas the cytoplasmic levels of both HuR and AUF1 protein increased. Immunoprecipitation of HuR-RNA complexes followed by reverse transcriptase-PCR analysis showed that HuR interacted with ATF3 mRNA in vivo and that this interaction increased following amino acid limitation. In contrast, the interaction of AUF1 with the ATF3 mRNA is decreased in histidine-deprived cells relative to control cells. Suppression of HuR expression by RNA interference partially blocked the accumulation of ATF3 mRNA following amino acid deprivation. The results demonstrated that coordinated regulation of mRNA stability by HuR and AUF1 proteins contributes to the observed increase in ATF3 expression following amino acid limitation.

3' Untranslated Regions↗
PubMed2001

The CANON system (Completely Autotrophic Nitrogen-removal Over Nitrite) under ammonium limitation: interaction and competition between three groups of bacteria.

The CANON system (Completely Autotrophic Nitrogen Removal Over Nitrite) can potentially remove ammonium from wastewater in a single, oxygen-limited treatment step. The usefulness of CANON as an industrial process will be determined by the ability of the system to recover from major disturbances in feed composition. The CANON process relies on the stable interaction between only two bacterial populations: Nitrosomonas-like aerobic and Planctomycete-like anaerobic ammonium oxidising bacteria. The effect of extended periods of ammonium limitation was investigated at the laboratory scale in two different reactor types (sequencing batch reactor and chemostat). The lower limit of effective and stable nitrogen removal to dinitrogen gas in the CANON system was 0.1 kg N m(-3) day(-1). At this loading rate, 92% of the total nitrogen was removed. After prolonged exposure (> 1 month) to influxes lower than this critical NH4+-influx, a third population of bacteria developed in the system and affected the CANON reaction stoichiometry, resulting in a temporary decrease in nitrogen removal from 92% to 57%. The third group of bacteria were identified by activity tests and qualititative FISH (Fluorescence In Situ Hybridisation) analysis to be nitrite-oxidising Nitrobacter and Nitrospira species. The changes caused by the NH4+-limitation were completely reversible, and the system re-established itself as soon as the ammonium limitation was removed. This study showed that CANON is a robust system for ammonium removal, enduring periods of up to one month of ammonium limitation without irreversible damage.

Bacteria, Anaerobic↗
PubMed1994

Postural effects on biomechanical and psychophysical weight-lifting limits.

Many believe that biomechanical models and data are not sufficiently refined and validated to be used as the basis for setting 'safe' population load lifting limits. Rather, they advocate that such limits should be based on what a sample of the population demonstrate to be 'maximum acceptable weight limits' (MAWL) resulting from psychophysical tests performed with different populations. Yet, biomechanical models are becoming more robust and valid. Computerized versions of these models are readily available, and these models now can provide a more complete understanding of the pathophysiology of a person's spinal column and supporting structures, thereby providing a means to predict the risk of tissue trauma in given lifting situations for large size populations. NIOSH has recognized the validity of both biomechanics and psychophysics for establishing a Recommended Weight Limit (RWL) in the United States. The implications of using both types of methods and data are explored in this paper. Three case studies are presented that involve infrequent lifting of varied size boxes from near floor level to explore how MAWL and biomechanically determined limits differ. The cases include symmetric, sagittal plane lifting using a freestyle posture, a similar lift but with freestyle and squat lift postures, and an asymmetric load lifting task. In all three case comparisons it is shown that a recommended load to be lifted based solely on a spinal disc compression force tolerance of 3400 N would be much lower than published MAWL values representing 75% or even 90% of young males under 40 years old (i.e. MAWL values may not be protective of some young males). It also is shown that MAWL values do not have as much population variance as the spinal motion segment failure values. Hence, many younger males would be expected to have spinal columns that can tolerate the highest published MAWL values. Several mitigating factors, including load lifting trajectories, lifting dynamics, and biomechanical modeling limitations are discussed, as well as differences in compressive force tolerances and MAWLs associated with age and gender.

Adult↗
PubMed2005

Driving under the influence of drugs in Sweden with zero concentration limits in blood for controlled substances.

OBJECTIVE: This article describes the background and implementation in Sweden of zero-concentration limits for controlled drugs in the blood of drivers. Eliminating the need to prove that a person's ability to drive safely was impaired by drugs has greatly simplified the prosecution case, which now rests primarily on the forensic toxicology report. Driving under the influence of a prescription drug listed as a controlled substance is exempt from the zero-limit law provided the medication was being used in accordance with a physician's direction and the person was not considered unfit to drive. METHODS: The prevalence of driving under the influence of drugs (DUID) in Sweden was evaluated from police reports with the main focus on the toxicological findings. A large case series of DUID suspects was compared before and after introducing zero concentration limits in blood for controlled substances on July 1, 1999. The spectrum of drugs used by typical offenders and the concentrations of various licit and illicit substances in blood were evaluated and compared. RESULTS: Immediately after the zero-limit law came into force, the number of cases of DUID submitted by the police for toxicological analysis increased sharply and is currently ten-fold higher than before the new legislation. Statistics show that about 85% of all blood samples sent for toxicological analysis have one or more banned substances present. Amphetamine is by far the leading drug of abuse in Sweden and was identified in about 50-60% of all DUID suspects either alone or together with other controlled substances. The next most frequently encountered illicit drug was tetrahydrocannabinol (THC), with positive findings in about 20-25% of cases. Various prescription drugs, mainly sedative-hypnotics like diazepam and flunitrazepam, were also highly prevalent and these occurred mostly together with illicit substances. Opiates, such as 6-acetyl morphine and morphine, the metabolites of heroin, were high on the list of substances identified. Most DUID suspects in Sweden were men (85%) who were poly-drug users combining illicit substances, like amphetamine and/or cannabis, with a prescription medication such as various benzodiazepines. CONCLUSIONS: Sweden's zero-concentration limit has done nothing to reduce DUID or deter the typical offender because recidivism is high in this population of individuals (40-50%). Indeed, many traffic delinquents in Sweden are criminal elements in society with previous convictions for drunk and/or drugged driving as well as other offenses. The spectrum of drugs identified in blood samples from DUID suspects has not changed much since the zero-limit law was introduced.

Automobile Driving↗
PubMed2006

Do recommended driving limits affect teen-reported traffic violations and crashes during the first 12 months of independent driving?

OBJECTIVES: Motor vehicle crashes are highly elevated among newly licensed teenage drivers. Limits on high-risk driving conditions by driver licensing policies and parents can protect novice teens from negative driving outcomes, while they experience and driving proficiency. The purpose of this research was to evaluate the effects of strict parent-imposed driving limits on driving outcomes during the first year of licensure. METHODS: A sample of 3,743 Connecticut teens was recruited and randomized to the Checkpoints Program or comparison condition. Assessments conducted at baseline, licensure, 3-, 6-, and 12-months postlicensure included parent-imposed driving limits, traffic violations, and crashes. Bivariate and multivariate analyses were conducted to assess the effects of strict parent limits on traffic violations and crashes during the first year of licensure. RESULTS: Thirty percent of teens reported at least one traffic violation and 40% reported at least one crash. More strict parent-imposed limits at licensure, 3-, 6-, and 12-months postlicensure, were associated with fewer violations and crashes in multivariate analyses. Notably, adherence to recommended night curfew was consistently associated with fewer violations and crashes. CONCLUSIONS: The findings indicate that strict parent-imposed limits may protect novice teen drivers from negative driving outcomes.

Accidents, Traffic↗
PubMed2004

Habitat size, recruitment, and longevity as factors limiting population size in stage-structured species.

Surprisingly little research has evaluated how habitat size may limit the population size of species that use different habitats at different stages of their lives. Here we develop simple discrete-time models to describe the population dynamics of species that use separate juvenile and adult habitats. Analytic solutions, model simulations, and elasticity and sensitivity analyses show that adult abundance is only limited by the size of the juvenile habitat when both adult habitat size and recruitment are much larger than juvenile habitat size. Juvenile habitat plays a marginally greater role in limiting population size for species with closed populations, where recruitment is proportional to adult abundance, versus open populations. Because adult populations often accumulate pulses of juveniles, adult habitat size can strongly limit population size over a broad range of parameter values, an effect that increases as the longevity of a species increases. Limited empirical research from a range of taxa supports these model predictions, although few studies were designed to actually test the limiting role of juvenile versus adult habitat. Future research must carefully evaluate whether and how processes at the juvenile stage affect adult abundance, and conservation efforts may be able to use this model to evaluate the cost-effectiveness, vis-a-vis increasing adult abundance, of time and money allocated to protecting juvenile habitats.

Animals↗
PubMed2005

Empirical models of pollen limitation, resource acquisition, and mast seeding by a bee-pollinated wildflower.

Synchronous mast seeding is increasingly recognized as common in plant populations. Recent theoretical models show that synchronous mast seeding could be a consequence of resource allocation and storage within individual plants, coupled by pollen limitation in low-flowering years. We used long-term population and weather data to parameterize models of flowering based on stored resources and pollen limitation in Astragalus scaphoides, a bee-pollinated plant that flowers in alternate years. We used these models to test whether internal resource dynamics could explain mast seeding in A. scaphoides and, if so, whether synchrony was caused by pollen limitation and/or fluctuations in precipitation. We compared predictions of models that included all combinations of three factors: constant versus precipitation-dependent resource gain, uniform versus heterogeneous resource gain (among individual plants), and resource-dependent versus resource- and pollen-limited fruit set. Pollen limitation and heterogeneous resource gain were necessary and sufficient to explain alternate-year flowering, but precipitation increased the quantitative match between model predictions and flowering dynamics. Together, our results support the importance of density-dependent pollen limitation as an ultimate and proximate cause of mast seeding in A. scaphoides. Precipitation does not act as a direct cue for synchrony in this species but might affect long-term resource gain and fruiting dynamics.

Animals↗
PubMed1996

Limiting values of backscatter factors for low-energy x-ray beams.

Models for the calculation of upper and lower limiting values to the backscatter factor (BSF) are presented. The upper limit is obtained from Monte Carlo simulations of infinite parallel beams incident on semi-infinite phantoms with the dose contributions from all orders of photon scatter considered. The lower limits are calculated using an analytical photon transport model which considers only the primary dose and the scatter dose from photons that have undergone single scattering interactions in the phantom. The limiting values can be used to evaluate measured and modelled BSF values for x-ray beams with photons of < or = 150 keV. A parametrization of the limiting values in terms of photon energy and irradiation field size is presented so that results determined for monoenergetic beams can be extended to polyenergetic spectra. The utility of the limits is illustrated by comparisons made with BSFs from the literature.

Humans↗
PubMed1998

A method of limited replication for the efficient in vivo delivery of adenovirus to cancer cells.

Replication-deficient viral vectors are currently being used in gene transfer strategies to treat cancer cells. Unfortunately, viruses are limited in their ability to diffuse through tissue. This makes it virtually impossible to infect the majority of tumor cells in vivo and results in inadequate gene transfer. This problem can be addressed by allowing limited viral replication. Limited viral replication facilitates greater penetration of virions into tissue and can improve gene transfer. We have developed a strategy of limited viral replication using AdRSVlaclys, a chemically modified E1-deleted adenovirus, to codeliver an exogenous plasmid encoding the adenovirus E1 region. This system allows one round of viral replication. We examined the effect of this limited adenovirus replication in vitro and in vivo. In culture, codelivery of virus and pE1 resulted in a large increase in infected cells when compared with control cells exposed to virus and pUC19. In experiments on nude mice bearing HeLa ascites tumors, intraperitoneal injection of AdRSVlaclys/pE1 resulted in a significantly higher percentage of infected HeLa cells as compared with the PBS controls (p < 0.05) or the AdRSVlaclys/pUC19 controls (p < 0.01). These data demonstrate that the transcomplementation of replication-deficient adenovirus with exogenous E1 DNA leads to limited replication, and this controlled replication enhances gene transfer efficiency of adenovirus in vivo.

Adenoviridae↗
PubMed1997

Effect of body mass index on activity limitation and mortality among older women: the National Health Interview Survey, 1986-1990.

We assessed the impact of body mass on the association between activity limitations due to chronic conditions and mortality among 24,612 noninstitutionalized white or African American women aged > or = 65 years who participated in a National Health Interview Survey between 1986 and 1990. We found that more African American women had activity limitations than white women (59% vs 46%, respectively). The difference by race was greatest (19% vs 10%) for the most severe limitation (unable to perform the major activity). For women aged 65-69, the major activity was working or keeping house; for those aged > or = 70, it was the ability to live independently. For white women in all three categories of body mass index (BMI) and for African American women with BMI 15%-85%, the risk of dying was significantly higher for those unable to perform the major activity than for those with no limitations, controlling for the effects of education, marital status, and perceived health. The findings confirm the established link between low BMI and mortality and between activity limitations and mortality. Additionally, the findings further suggest that activity limitations linked to chronic conditions increase the risk of death within each stratum of BMI after adjusting for potential confounders.

Activities of Daily Living↗
PubMed2000

Limiting comorbid conditions and breast cancer stage at diagnosis.

BACKGROUND: Contrasting hypotheses exist regarding the relationship between comorbidity and breast cancer stage at diagnosis. One suggestion is that disabling comorbid conditions would result in a later stage diagnosis of breast cancer because such conditions would limit mobility and thus access to medical care. This article examines this hypothesis by building a comorbidity summary measure of functionally limiting comorbid conditions and by testing the effectiveness of this measure in predicting the stage at which breast cancer is diagnosed. METHODS: Cases with newly diagnosed breast cancer were identified through the population-based Metropolitan Detroit Cancer Surveillance System, a participant of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Of 1191 eligible cases, 1011 (85%) were interviewed 2-4 months following diagnosis. The analyses for this study were limited to 731 cases for which there were complete data on all variables. Five individual comorbid conditions that predicted functional limitation were combined into a comorbidity summary measure: arthritis, eye conditions, gastrointestinal conditions, kidney conditions, and respiratory conditions. Breast cancer stage was categorized in relation to whether women had local or advanced (regional or remote) disease. RESULTS: Women with two or more of these five functionally limiting conditions were about half as likely as those with none of these conditions to receive an advanced stage diagnosis of breast cancer (odds ratio [OR] = 0.49, 95% confidence interval [CI] 0.28-0.86, p = .01). CONCLUSIONS: These findings do not support the suggestion that the presence of disabling comorbid conditions results in later stage breast cancer. The five conditions summarized by this measure, although functionally limiting, may also require greater medical monitoring due to associated symptoms and/or treatment requirements and thus lead to increased opportunities for cancer screening.

Adult↗
PubMed2002

The 6-minute walk test in mobility-limited elders: what is being measured?

BACKGROUND: The 6-minute walk (6mw) is a well-established measure of aerobic capacity in elders with cardiorespiratory and peripheral vascular disease and may be an accurate measure of functional performance in healthy elders. In mobility-limited elders, a population at risk for disability, impairments in strength and power are predictive of performance-based measures of function. Though commonly utilized as an outcome measure among otherwise healthy mobility-limited elders, it is not clear whether the 6mw best represents a measure of functional limitation, aerobic capacity, or both. METHODS: We hypothesized that the 6mw would be strongly representative of performance-based measures of function being determined by impairments in muscle strength and power. We performed a cross-sectional analysis of 45 community-dwelling elders with mild to moderate mobility limitations. RESULTS: The 6mw was strongly associated with established functional measures (r =.61-.83; p <.001), but was poorly associated with indirect measures of aerobic capacity (r <.25; p >.05). Multivariate linear regression models demonstrated that impairments in leg strength and power, especially those at the knee and ankle, were predictive of 6mw performance. CONCLUSIONS: These findings emphasize the 6mw as a measure of functional limitation among mobility-limited elders without cardiorespiratory or peripheral vascular disease.

Activities of Daily Living↗
PubMed2004

Reasons given by older people for limitation or avoidance of driving.

PURPOSE: To understand the driving behavior of older adults, this study examines self-reported reasons for driving limitation or avoidance. DESIGN AND METHODS: Baseline interviews were conducted (n = 2,046) as part of a community-based study of aging and physical performance in persons aged 55 years or older in Sonoma, California. Twenty-one medical and nonmedical reasons for limiting or avoiding driving were examined by age and gender. RESULTS: Most older people continue to drive; however, many, especially older women, report one or more reasons to limit or avoid driving. Among medical reasons, problems with eyesight are by far the most often cited; no other health problem was identified as a major reason for limitation. Among nonmedical reasons, being concerned about an accident, being concerned about crime, and having no reason to drive were often cited. Important predictors of reported driving limitations were low income, limited functional status, and self-report of poor vision. IMPLICATIONS: Understanding factors that affect driving patterns in older adults, including medical and nonmedical reasons, will assist in developing both enhancements to extend safe driving years and responses to the consequences of driving reduction.

Activities of Daily Living↗