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PubMed2006

Proteome analysis of yeast response to various nutrient limitations.

We compared the response of Saccharomyces cerevisiae to carbon (glucose) and nitrogen (ammonia) limitation in chemostat cultivation at the proteome level. Protein levels were differentially quantified using unlabeled and 15N metabolically labeled yeast cultures. A total of 928 proteins covering a wide range of isoelectric points, molecular weights and subcellular localizations were identified. Stringent statistical analysis identified 51 proteins upregulated in response to glucose limitation and 51 upregulated in response to ammonia limitation. Under glucose limitation, typical glucose-repressed genes encoding proteins involved in alternative carbon source utilization, fatty acids beta-oxidation and oxidative phosphorylation displayed an increased protein level. Proteins upregulated in response to nitrogen limitation were mostly involved in scavenging of alternative nitrogen sources and protein degradation. Comparison of transcript and protein levels clearly showed that upregulation in response to glucose limitation was mainly transcriptionally controlled, whereas upregulation in response to nitrogen limitation was essentially controlled at the post-transcriptional level by increased translational efficiency and/or decreased protein degradation. These observations underline the need for multilevel analysis in yeast systems biology.

Ammonia↗
PubMed2005

Role of weight history on functional limitations and disability in late adulthood: the ARIC study.

OBJECTIVE: To examine associations of weight history with functional limitations and disability in white and African-American men and women. RESEARCH METHODS AND PROCEDURES: Data were from the Atherosclerosis Risk in Communities study (n = 11,177). Associations of recalled weight status at age 25 and weight change from age 25 to ages 45 to 64 with functional limitations, activities of daily living (ADLs), and instrumental activities of daily living (IADLs) at follow-up (ages 52 to 75) were examined using logistic regression. RESULTS: Obesity (BMI > or = 30 kg/m2) at age 25 was associated with functional limitations and ADL and IADL impairment at follow-up in white and African-American men and women. For example, obese compared with normal weight (BMI, 18.5 to 24.9 kg/m(2)) white women had higher odds of mild [odds ratio (95% confidence interval), 1.97 (1.18 to 3.29)] and severe [9.81 (5.92 to 16.27)] functional limitations and ADL [3.48 (2.36 to 5.13)] and IADL [2.95 (2.00 to 4.33)] impairment. In African-American women, obesity was associated with higher odds of mild [2.71 (1.14 to 6.41)] and severe [6.01 (2.53 to 14.26)] functional limitations and ADL [1.82 (1.10 to 3.00)] and IADL [2.39 (1.47 to 3.90)] impairment. Similar associations were found in men. Compared with weight maintenance (+/-10 lbs), large weight gain (>30 lbs) from age 25 to ages 45 to 64 was also associated with functional limitations and ADL and IADL impairment in white and African-American men and women. DISCUSSION: Maintenance of a healthy body weight throughout adulthood may play a role in preventing or delaying the onset of functional limitations and disability, resulting in increased quality of life and decreased health care costs.

Activities of Daily Living↗
PubMed1997

Limited vs full microbiological investigation for the management of symptomatic polymicrobial urinary tract infection in adult spinal cord-injured patients.

Spinal cord-injured (SCI) patients often suffer from symptomatic polymicrobial urinary tract infection (UTI). The objective of this study was to evaluate the clinical outcome and cost-savings associated with antibiotic therapy based on limited vs full microbiological investigation of urine cultures in adult SCI patients with symptomatic polymicrobial UTI (> or = 2 organisms growing in urine cultures). In the first part of the study, a total of 40 evaluable patients were prospectively randomized in a single-blinded fashion to receive antibiotic therapy based on either limited (21 patients) or full microbiologic investigation (19 patients) of urine cultures. The practicality of a limited microbiological investigation was further examined in the second part of the study where 12 consecutive patients with symptomatic polymicrobial UTI initially had only limited microbiological investigation of urine cultures and received antibiotic therapy accordingly. When analyzing all patients in the study, the likelihood of adequate clinical response was not significantly different between those who received antibiotic therapy based on limited (28/33 = 85%) vs full (18/19 = 95%) microbiological investigation of urine cultures (P = 0.40). An average of 183 US dollars could be saved per patient by managing symptomatic polymicrobial UTI based on a limited vs a full microbiological investigation. These results suggest that in adult SCI patients with symptomatic polymicrobial UTI antibiotic therapy guided by a limited microbiological investigation may be practical, adequate and cost-saving.

Adult↗
PubMed2000

Influence of different substrate limitations on the yield, composition and molecular mass of exopolysaccharides produced by Lactococcus lactis subsp. cremoris in continuous cultures.

The type of substrate limitation had a remarkable influence on the molecular mass of exopolysaccharides (EPS) produced by Lactococcus lactis subsp. cremoris NIZO B40 and NIZO B891. Under glucose/energy limitation, the molecular mass was much smaller than under leucine or phosphate limitation, resulting in a marked decrease of the intrinsic viscosity of this EPS. The sugar composition of EPS produced by both strains, and the phosphate content of EPS produced by NIZO B40, were not affected by the type of nutrient limitation. Both strains produced comparable amounts of EPS under leucine and glucose limitation, but the efficiency of EPS production was highest under glucose limitation. The EPS yields of the phosphorylated B40 EPS as well as the unphosphorylated B891 EPS were reduced, with about 40% under conditions of phosphate limitation.

Carbohydrate Sequence↗
PubMed2001

New normal limits for the paediatric electrocardiogram.

AIMS: Previous studies that determined the normal limits for the paediatric ECG had their imperfections: ECGs were recorded at a relatively low sampling rate, ECG measurements were conducted manually, or normal limits were presented for only a limited set of parameters. The aim of this study was to establish an up-to-date and complete set of clinically relevant normal limits for the paediatric ECG. METHODS AND RESULTS: ECGs from 1912 healthy Dutch children (age 11 days to 16 years) were recorded at a sampling rate of 1200 Hz. The digitally stored ECGs were analysed using a well-validated ECG computer program. The normal limits of all clinically relevant ECG measurements were determined for nine age groups. Clinically significant differences were shown to exist, compared with previously established normal limits. Sex differences could be demonstrated for QRS duration and several amplitude measurements. CONCLUSIONS: These new normal limits differ substantially from those commonly used and suggest that diagnostic criteria for the paediatric ECG should be adjusted.

Adolescent↗
PubMed2001

[Can the limits of intensive care management be defined?].

Medical treatment requires more than the application of techniques and devices. Knowing the limitations of (intensive) care and respecting patients' will and dignity is as important as technical skills. Limitations of therapy may arise from medical, ethical, legal, and economic reasons. Therapy may be limited through a Do-Not-Resuscitate (DNR) order, or by withholding or withdrawal of treatment. Total withdrawal of treatment ensues from proven brain death when organ donation has been denied or has been accomplished. But legislation as well as ethics and medical science fail to define unequivocal and precise criteria for limitation of treatment. Depending on the kind of disease, its prognosis and the patient's individual situation clinical scenarios can be identified when withholding or withdrawal of treatment may be thought of. The patient's expressed or anticipated wishes play a key role in decision-making on limitation of treatment. If the patient has no more decision making capacities physicians and patient's next of kin have to determine what would be in the patient's best interest. The patient and/or his family, all attending physicians and the nursing staff have to agree when limitation of care is taken into account. Hospital guidelines and written orders will help physicians and nursing staff to manage these difficult situations. Whether treatment has been limited or not, the patient and his family deserve all our medical and psychological skills--until the end.

Critical Care↗
PubMed2002

Control of long-period orbits and arbitrary trajectories in chaotic systems using dynamic limiting.

We demonstrate experimental control of long-period orbits and arbitrary chaotic trajectories using a new chaos control technique called dynamic limiting. Based on limiter control, dynamic limiting uses a predetermined sequence of limiter levels applied to the chaotic system to stabilize natural states of the system. The limiter sequence is clocked by the natural return time of the chaotic system such that the oscillator sees a new limiter level for each peak return. We demonstrate control of period-8 and period-34 unstable periodic orbits in a low-frequency circuit and provide evidence that the control perturbations are minimal. We also demonstrate control of an arbitrary waveform by replaying a sequence captured from the uncontrolled oscillator, achieving a form of delayed self-synchronization. Finally, we discuss the use of dynamic limiting for high-frequency chaos communications. (c) 2002 American Institute of Physics.

Journal Article↗
PubMed1995

Shift of a limit cycle in biology: From pathological to physiological homeostasia@f|

Biological systems may show homeostatic behaviors that are similar to the ones of forced dynamic systems with a stable limit cycle. For a large class of dynamic systems, it is shown that a shift of a pathological limit cycle over the physiological limit cycle can never be executed by means of a control with a desired periodicity. The above statement shows that the only possibility is to reduce as much as possible the dimensions of a small residual limit cycle. Moreover, it is possible to give some information about the structure of feedback laws that would allow the shift of the limit cycle. The fact that it is generally not possible to recover a physiological limit cycle from a pathological one, results into the fear of never or hardly ever reaching a physiological behavior, and it seems that any hope of therapeutics is given up. This leads to introduce the locking concept, which permits system parameters to change and provides the basis for an adaptive and iterative control, which allows a step by step approach and to finally reach the physiological limit cycle. (c) 1995 American Institute of Physics.

Journal Article↗
PubMed2003

Potential thrombophilic mutations/polymorphisms in patients with no flow-limiting stenosis after myocardial infarction.

BACKGROUND: Although inherited thrombophilias are more common in patients with venous thromboembolism, their influence on the development of myocardial infarction (MI) requires clarification. METHODS AND RESULTS: To determine whether there are increased frequencies of mutations/polymorphisms in 14 genes potentially causing thrombophilia in patients with no flow-limiting stenoses after MI compared with patients with > or =1 flow-limiting stenosis of >50%, we studied 395 patients (60 with no flow-limiting stenosis) who underwent angiography at approximately 1 month. The mutations/polymorphisms studied included Factor V Leiden, prothrombin variant G20210A, beta-fibrinogen 448 (G/A), endothelial protein C receptor (23-base pair insertion), methyl tetrahydrofolate reductase 677 (C/T), platelet glycoprotein IIIa PlA1/A2, plasminogen activator inhibitor-1 4G/5G, angiotensin II type 1 receptor (A/C), hemochromatosis gene 282 (G/A), nitric oxide synthase (NOS) (3 forms: eNOS, eNOS3, eNOS4), p22 phox of NADPH oxidase C242T, and angiotensin-converting enzyme insertion/deletion polymorphism. The frequencies of Factor V Leiden and the beta-fibrinogen 448 A allele were higher in patients with no flow-limiting stenosis than in patients with > or =1 stenosis (11.7% vs 3.6%, odds ratio [OR] 3.6, 95% CI 1.3-9.4, P =.015; and 42% vs 27%, OR 2.0, 95% CI 1.1-3.5, P =.018, respectively), and there was a trend toward an increased frequency of prothrombin variant G20210A (6.7% vs 2.1%, OR 3.4, 95% CI 0.95-11.8, P =.069). However, in patients with no flow-limiting stenosis after MI the frequencies of the other gene mutations/polymorphisms were not increased. Also, there were no significant interactions between any of these 14 mutation/polymorphisms, major cardiovascular risk factors, and the absence of any flow-limiting stenosis, except for Factor V Leiden and hypertension (OR 6.34, 95% CI 2.67-100, P =.004). CONCLUSIONS: Patients with no flow-limiting stenosis after MI had increased frequencies of 2 inherited thrombophilias (Factor V Leiden and beta-fibrinogen 448 A allele), and there was a trend toward an increased frequency of prothrombin variant G20210A compared with patients with > or =1 stenosis. These data suggest that polymorphisms/mutations in some gene products influencing coagulation may influence the pathogenesis of MI.

Adult↗
PubMed2000

Indications for limited echocardiographic imaging: a mathematical model.

BACKGROUND: Few data exist on the magnitude of potential time savings obtained by using a limited echocardiographic (echo) imaging strategy on a referral population. METHODS: A mathematical model of a limited echo screening strategy was devised that used as variables the length of the limited examination and the probability of detecting the referral diagnosis or a significant incidental finding, and assumed that any abnormality would mandate a full study. Data from prior echo population studies were used in the model as examples. RESULTS: The model demonstrated a direct relation in time savings for populations with a low prevalence of disease and incidental findings. The model predicted that a limited echo imaging strategy could result in significant time savings when applied to certain specific referral populations. CONCLUSIONS: The time savings of a limited echo screening strategy can be modeled as a function of the length of the limited screen and the presence of significant findings. This model may provide the framework in which future prospective studies can confirm indications for limited echo.

Cardiovascular Diseases↗
PubMed2002

Limited cardiac ultrasound examination for cost-effective echocardiographic referral.

BACKGROUND: Although a standard echocardiogram is frequently requested and requires significant resources, few data exist on methods to improve referral for this examination. Therefore, we sought to determine the diagnostic value of a limited echocardiographic examination and to predict the cost-effectiveness of a limited imaging strategy on echocardiographic referral. METHODS: A limited echocardiographic examination was reviewed for abnormalities and compared with standard echocardiographic findings. Assuming an imaging strategy in which a normal limited echocardiographic examination would negate the need for standard echocardiography, we calculated the diagnostic yields, the number of full echocardiographic studies eliminated, and the number of abnormal cases missed. We also stratified data by patient age (< or > or = 65 years), inpatient versus outpatient status, gender, referral diagnosis, and referring physician subspecialty. RESULTS: In 151 outpatients, overall diagnostic yield was 47% (95% CI [39%, 55%]), and was lower in those younger than 65 years, in women, and in noncardiologist referral. In 155 inpatients, yields were 75% (95% CI [67%, 83%]) and were also related to age, but not to gender, diagnosis, and physician subspecialty. Sensitivity, specificity, negative and positive predictive values, and accuracy for the limited echocardiographic examination was 77%, 72%, 67%, 81%, and 75%, respectively. The limited imaging strategy negated 70% of studies in the outpatient group younger than 65 years, with a less than 5% chance of missing a clinically significant finding. CONCLUSION: A limited echocardiographic imaging strategy is most cost-effective when used in young outpatients, where it can result in a substantial reduction in referral for standard echocardiography while rarely missing findings.

Aged↗
PubMed2006

Perceiving surfaces in depth beyond the fusion limit of their elements.

An isolated dot appears double outside a small disparity range called Panum's fusional area. In random-dot stereograms (RDSs), however, this doubling, or diplopia of dot elements is not evident at any disparity. Nevertheless, depth is perceived up to disparities that greatly exceed Panum's fusional limit. Either one is unaware of dot diplopia at disparities exceeding Panum's fusional limit or the fusion limit is extended. To examine these possibilities, we developed a novel RDS in which dichoptically color-coded dots have a distinctive color when fused, and return to their intrinsic colors when diplopic. We measured the fusion limit of dots in this RDS, and compared it to the patent stereopsis limit of the perceived surface in similar RDSs. We found that the fusional area of dots in the RDS was comparable to Panum's fusional area. Furthermore, there was clear dissociation between the fusion limit and the patent stereopsis limit in the RDS. We conclude that the elements composing a surface are not necessarily fused when a large disparity surface is perceived in depth.

Depth Perception↗
PubMed1989

Form and exploration of mechanical stability limits in erect stance.

The stability limits of erect stance are described as a geometrical structure in a movement space. Mechanical properties and response latency, a neural property, are determining factors for the stability limits. Standing stability limits of adults and young children are compared, and a simple scheme is suggested by means of which infants can discover the stability limits as they learn to stand. The mechanics of different standing movements are discussed because their spatial temporal properties relate directly to their different stability limits. The combination of the stability limits for different movements gives a total set of stability limits, a different structure for adults than for children.

Journal Article↗
PubMed2000

A national survey of health-related work limitations among employed persons in the United States.

PURPOSE: To estimate the total prevalence of health-related work limitations among working people in the United States (US) as well as their condition-specific prevalence. METHODS: A new questionnaire measuring limitations in ability to perform specific work demands was administered to 940 employed people in a national household survey. The prevalence of specific work limitations is reported as are condition-specific risk estimates (odds ratios) based on logistic regression. RESULTS: In the US, 19.3% of working people (CI = 14.0, 24.6) were limited in their abilities to perform physical work demands; 24.1% (CI = 18.9, 29.2) were limited in performing psychosocial work demands; and 13.8% (CI = 8.3, 19.3) were limited in their abilities to function without difficulty within the ambient work environment. With successive increments in the number of conditions, the odds of having a limitation increased significantly. CONCLUSIONS: This study contributes new information concerning the implications of chronic health problems for working people and the significant risks for workers with multiple chronic conditions.

Adult↗
PubMed2004

Imputation of data values that are less than a detection limit.

Results of the analyses of occupational and environmental samples are frequently reported as "less than a specified value," a practice followed by many analytical laboratories. A left-censored distribution occurs when analytical laboratories do not report results that fall below their limits of detection or quantification. Approximately 37% of the household interior dust lead loadings collected in a large-scale, multisite, longitudinal study of lead-based paint hazard controls were reported to be below the "method detection limit." These unreported values are unusable in any statistical analysis of the data and must be replaced by a valid dust lead loading estimate, a process called data imputation. This investigation tested how well data imputed using a newly formulated procedure for estimating the data below the method detection limit were correlated with dust lead loadings reported by the participating laboratories after special request. These results were also compared with those obtained by imputing the minimum detectable level by the square root of 2. Imputation of the low lead loadings was accomplished by substituting the value associated with the median percentile below each laboratory's method detection limit. A correlation of r = 0.50 was calculated between the predicted and reported dust lead loadings, with only slight bias (2.9%) in the predicted values. An alternative imputation procedure that used the predicted value from structural equation models fit to the noncensored dust lead loadings performed about as well, although the predictions had to be "centered" to correspond to the censored data. An estimator that combined both of these imputation procedures only slightly improved the correlation between the predicted and laboratory values (r = 0.51). These results support the use of the new procedure rather than the commonly used imputed values of the method detection limit divided by 2 or by the square root of 2. Imputing values based on either of these common approaches may result in much more biased predictions for the censored data; in the case of these data, the dust lead loadings were overestimated by 348%. The results also suggest that analytical laboratories should provide a numerical result for all analyzed samples, with a "flag" of those values below their detection limit, since these results may be more accurate than any imputed value, particularly those provided by the commonly used method of dividing the minimum detection limit by the square root of 2.

Air Pollutants↗
PubMed1989

Effects of mutation on selection limits in finite populations with multiple alleles.

The ultimate response to directional selection (i.e., the selection limit) under recurrent mutation is analyzed by a diffusion approximation for a population in which there are k possible alleles at a locus. The limit mainly depends on two scaled parameters S (= 4Ns sigma a) and theta (= 4Nu) and k, the number of alleles, where N is the effective population size, u is the mutation rate, s is the selection coefficient, and sigma 2a is the variance of allelic effects. When the selection pressure is weak (S less than or equal to 0.5), the limit is given approximately by 2S sigma a[1 - (1 + c2)/k]/(theta + 1) for additive effects of alleles, where c is the coefficient of variation of the mutation rates among alleles. For strong selection, other approximations are devised to analyze the limit in different parameter regions. The effect of mutation on selection limits largely relies on the potential of mutation to introduce new and better alleles into the population. This effect is, however, bounded under the present model. Unequal mutation rates among alleles tend to reduce the selection limit, and can have a substantial effect only for small numbers of alleles and weak selection. The selection limit decreases as the mutation rate increases.

Alleles↗
PubMed2005

Weight change, weight change intention, and the incidence of mobility limitation in well-functioning community-dwelling older adults.

BACKGROUND: Obesity increases the risk for functional decline in later years, but the functional consequences of weight change in older adults are currently unclear. The aim of this study was to determine whether weight, weight change, and weight change intention are associated with risk for mobility limitation in elderly persons. METHODS: This study included 2,932 well-functioning black and white men and women aged 70 to 79 years, participating in the Health, Aging and Body Composition (Health ABC) Study, who were followed for 30 months. At baseline, reported weight change of 5 or more pounds during the previous year and weight change intention were assessed. Mobility limitation was defined as reported difficulty or inability to walk one-quarter mile or to climb 10 steps during two consecutive semiannual assessments during a period of 30 months. RESULTS: Approximately 30% of participants developed mobility limitation. Higher body mass index (BMI) was associated with increased risk for mobility limitation. Unintentional weight loss in the previous year was associated with increased risk for mobility limitation in the extremely obese, which was defined as BMI >or= 35 (hazard ratios [HR], =3.79; 95% confidence interval [CI], 1.84--7.79), and the normal BMI, which was defined as BMI<25 (HR, 2.55; 95% CI, 1.80--3.60). In persons with BMI 25 to 29.9, intentional weight loss (HR, 1.59; 95% CI, 1.12--2.25) and weight fluctuation with any intention (HR, 1.59; 95% CI, 1.10--2.28) increased the risk for mobility limitation. Unintentional weight gain or fluctuation did not confer additional risk for mobility limitation compared with weight stability, regardless of the level of body weight. CONCLUSION: In this cohort of well-functioning elderly persons, functional consequences of past weight change depended on the type of weight change, intentionality, and current measured body weight.

Aged↗
PubMed2004

The effects of residential mobility on ADL and IADL limitations among the very old living in the community.

OBJECTIVES: We attempt to understand the influence of residential mobility on changes in objective activity of daily living (ADL) and instrumental ADL (IADL) limitations, while taking into account the subjective reason for the move. METHODS: We examine noninstitutionalized adults aged 70 and older who are in the Longitudinal Study of Aging. We use bivariate regression to identify differences between nonmovers and various types of movers in 1988 and 1990 ADL and IADL limitations. Multivariate residualized regression models estimate the effect of residential mobility on the changes in limitations between 1984-1988 and 1988-1990. We give particular attention to the timing and reason for the move. RESULTS: Controlling for demographic, social support, health status, and social integration characteristics, we find that residential mobility is associated with a short-term increase in ADL and IADL limitations. However, an additional analysis reveals that this short-term increase in limitations is only experienced by older adults who move for subjective health reasons. Compared with nonmovers, movers do not have significantly different changes in limitations over the long term. DISCUSSION: Older adults and service providers need to be concerned with short-term increases in objective ADL and IADL limitations that accompany residential relocations, especially for those who move for subjective health reasons. However, from a long-term perspective, residential relocation may serve as a mechanism for accommodating age-related changes that threaten effective functioning.

Activities of Daily Living↗