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PubMed1995

Transient rheological behavior of blood in low-shear tube flow: velocity profiles and effective viscosity.

Velocity profiles of human blood flowing through vertical and horizontal glass tubes (25-100 microns ID) were measured as a function of time following a sudden reduction of wall shear stress (tau w) from a high value to values ranging from 2 to 100 mPa. Cell velocities at various radial positions were determined off-line from video recordings by digital image analysis. In vertical tubes, symmetric velocity profiles were obtained that developed increasing bluntness with time, particularly at lower tau w and in smaller tubes. In horizontal tubes, velocity profiles developed strong asymmetry as a function of time. Red blood cell (RBC) sedimentation was associated with uniform low flow velocities in the concentrating cell sediment, whereas faster flow and almost parabolic profiles were observed in the supernatant plasma region. Calculations of effective blood viscosity showed a decrease with time at low tau w in vertical tubes but an increase in horizontal tubes. The differences between profile shape and effective viscosity in vertical and horizontal tubes disappeared at tau w > 50 mPa. These findings are related to the cross-sectional distribution of RBC, which depends on RBC aggregation and sedimentation.

Blood Flow Velocity↗
PubMed2006

Metabolomic profiling of heat stress: hardening and recovery of homeostasis in Drosophila.

Frequent exposure of terrestrial insects to temperature variation has led to the evolution of protective biochemical and physiological mechanisms, such as the heat shock response, which markedly increases the tolerance to heat stress. Insight into such mechanisms has, so far, mainly relied on selective studies of specific compounds or characteristics or studies at the genomic or proteomic levels. In the present study, we have used untargeted NMR metabolomic profiling to examine the biological response to heat stress in Drosophila melanogaster. The metabolite profile was analyzed during recovery after exposure to different thermal stress treatments and compared with untreated controls. Both moderate and severe heat stress gave clear effects on the metabolite profiles. The profiles clearly demonstrated that hardening by moderate heat stress led to a faster reestablishment of metabolite homeostasis after subsequent heat stress. Several metabolites were identified as responsive to heat stress and could be related to known physiological and biochemical responses. The time course of the recovery of metabolite homeostasis mirrored general changes in gene expression, showing that recovery follows the same temporal pattern at these two biological levels. Finally, our data show that heat hardening permits a quicker return to homeostasis, rather than a reduction of the acute metabolic perturbation and that the reestablishment of homeostasis is important for obtaining maximal heat-hardening effect. The results display the power of NMR metabolomic profiling for characterization of the instantaneous physiological condition, enabling direct visualization of the perturbation of and return to homeostasis.

Adaptation, Physiological↗
PubMed2001

Methods for averaging irregular respiratory flow profiles in awake humans.

Respiratory flow profiles have been of interest as an output of the respiratory controller. In determining average flow profiles, however, previous methods that align individual breaths in the time domain are susceptible to distortions caused by the great variability, both between breaths and within breaths. We aimed to develop a method for determining typical flow profiles that circumvents such distortions. Our method aligns different breaths by phase of respiratory cycle, which is defined as the angle associated with the point on the normalized flow-volume diagram (a phase-plane plot). Over a number of breaths, median values for flow, volume, and elapsed time from the start of the breath at each phase angle are determined. Because these estimates are mutually semi-independent and in general violate the laws of mass balance, an adjustment was performed such that the volume was precisely the time integral of the flow. The method produced typical flow profiles with characteristics that were significantly closer to the mean values obtained from the individual cycles than those obtained by the technique of Benchetrit and co-workers (Benchetrit G, Shea SA, Dinh TP, Bodocco S, Baconnier P, and Guz A, Respir Physiol 75: 199-210, 1989), which reconstructs the typical flow profile from Fourier coefficients.

Humans↗
PubMed1998

Smoothness maximization along a predefined path accurately predicts the speed profiles of complex arm movements.

The speed profiles of arm movements display a number of regularities, including bell-shaped speed profiles in straight reaching movements and an inverse relationship between speed and curvature in extemporaneous drawing movements (described as a 2/3 power law). Here we propose a new model that simultaneously accounts for both regularities by replacing the 2/3 power law with a smoothness constraint. For a given path of the hand in space, our model assumes that the speed profile will be the one that minimizes the third derivative of position (or "jerk"). Analysis of the mathematical relationship between this smoothness constraint and the 2/3 power law revealed that in both two and three dimensions, the power law is equivalent to setting the jerk along the normal to the path to zero; it generates speed predictions that are similar, but clearly distinguishable from the predictions of our model. We have assessed the accuracy of the model on a number of motor tasks in two and three dimensions, involving discrete movements along arbitrary paths, traced with different limb segments. The new model provides a very close fit to the observed speed profiles in all cases. Its performance is uniformly better compared with all existing versions of the 2/3 power law, suggesting that the correlation between speed and curvature may be a consequence of an underlying motor strategy to produce smooth movements. Our results indicate that the relationship between the path and the speed profile of a complex arm movement is stronger than previously thought, especially within a single trial. The accuracy of the model was quite uniform over movements of different shape, size, and average speed. We did not find evidence for segmentation, yet prediction error increased with movement duration, suggesting a continuous fluctuation of the "tempo" of discrete movements. The implications of these findings for motor planning and on-line control are discussed.

Arm↗
PubMed2006

[Correlation of lipid profiles and anthropometric variables with serum lipoprotein(a) levels in childhood].

The aim of the present study was to evaluate lipoprotein(a) distribution in children and to assess its association with lipid profile and anthropometric variables. We studied 98 children (44 girls and 54 boys) with ages ranging from 6 to 7 years, who were included in an epidemiological study on the prevalence of hypercholesterolemia in children in the province of Biscay. The following parameters were determined: weight and height, body mass index, lipoprotein(a), and lipid profile. Lipid profile included total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, apolipoprotein B, and apolipoprotein A1. The mean and median serum lipoprotein(a) levels were 13.07 and 5.56 mg/dl respectively and were 11.43 and 3.92 mg/dl for boys and 15.09 and 8.32 mg/dl for girls. Lipoprotein(a) concentrations > 30 mg/dl were found in 7.4% of the boys and in 11.4% of the girls. The mean values and prevalences of lipoprotein(a) > 30 mg/dl were lower in boys than in girls but these differences were not statistically significant. A positive correlation was found between lipid profile (LDL-cholesterol, apolipoprotein B and LDL-cholesterol/HDL-cholesterol index) and lipoprotein(a) levels. When evaluating anthropometric variables, we found a statistically significant inverse correlation between weight and lipoprotein(a). In view of the cumulative effect of cardiovascular risk factors and the results of this study, we believe that lipoprotein(a) determination should be considered in children with an unfavorable lipid profile.

Anthropometry↗
PubMed2006

Examination of a CpG island methylator phenotype and implications of methylation profiles in solid tumors.

The CpG island methylator phenotype (CIMP), thoroughly described in colorectal cancer and to a lesser extent in other solid tumors, is important in understanding epigenetics in carcinogenesis and may be clinically useful for classification of neoplastic disease. Therefore, we investigated whether this putative phenotype exists in exposure-related solid tumors, where somatic gene alterations and enhanced clonal growth are selected for by carcinogens, and examined the ability of methylation profiles to classify malignant disease. We studied promoter hypermethylation of 16 tumor suppressor genes and 3 MINT loci (acknowledged classifiers of CIMP) in 344 bladder cancers, 346 head and neck squamous cell carcinomas (HNSCC), 146 non-small-cell lung cancer (NSCLC), and 71 malignant pleural mesotheliomas (MPM). We employed rigorous statistical methods to examine the distribution of promoter methylation and the usefulness of these profiles for disease classification. In bladder cancer, HNSCC, and NSCLC, there was a significant correlation (P < 0.0001) between methylation of the three MINT loci and methylation index, although the distribution of methylated loci varied significantly across these disease. Although there was a significant (P < 0.001) association between gene methylation profile and disease, rates of misclassification of each disease by their methylation profile ranged from 28% to 32%, depending on the classification scheme used. These data suggest that a form of CIMP exists in these solid tumors, although its etiology remains elusive. Whereas the gene profiles of hypermethylation among examined loci could not unequivocally distinguish disease type, the existence of CIMP and the relative preponderance of hypermethylation in these cancers suggest that methylation analysis may be clinically useful as a targeted screening tool.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Molecular marker profiles predict locoregional control of head and neck squamous cell carcinoma in a randomized trial of continuous hyperfractionated accelerated radiotherapy.

PURPOSE: Identification of factors that assist prediction of tumor response to radiotherapy may aid in refining treatment strategies and improving outcome. Possible association of molecular marker expression profiles with locoregional control of head and neck squamous cell carcinoma was investigated in a randomized trial of conventional versus continuous hyperfractionated accelerated radiotherapy (CHART). EXPERIMENTAL DESIGN: Tumor material was obtained from 402 patients. Immunohistochemistry was used to assess Ki-67, CD31, p53, Bcl-2, and cyclin D1 expression. A hierarchical clustering algorithm with a Bayesian information criterion was used to group tumors with similar marker expression; resulting expression profiles were then compared in terms of their difference in outcome after CHART and conventionally fractionated radiotherapy. RESULTS: Molecular marker profile was an independent prognostic factor for locoregional control. This was confirmed in multivariate analysis, including clinical variables such as tumor and nodal status, primary site, histological grade, age, and gender (P < 0.001 and P = 0.006 for local and nodal relapse, respectively). In particular, Bcl-2-positive tumors responded significantly better than average in both arms of the trial. Tumors negative for p53- and Bcl-2, with high and randomly patterned Ki-67 expression, responded worse than average with no benefit from CHART. Tumors with similarly negative p53 and Bcl-2, but low Ki-67 staining, with an organized pattern, benefit significantly from CHART schedule. CONCLUSIONS: This study demonstrates the potential of molecular profiles to predict radiotherapy response of head and neck squamous cell carcinoma and for treatment stratification. Distinct expression profiles correlate with three distinct clinical phenotypes, including good locoregional control, poor locoregional control, and an outcome strongly dependent upon fractionation schedule.

Algorithms↗
PubMed2004

Serum protein profile alterations in hemodialysis patients.

BACKGROUND: Serum protein profiling patterns can reflect the pathological state of a patient and therefore may be useful for clinical diagnostics. Here, we present results from a pilot study of proteomic expression patterns in hemodialysis patients designed to evaluate the range of serum proteomic alterations in this population. METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was used to analyze serum obtained from patients on periodic hemodialysis treatment and healthy controls. Serum samples from patients and controls were first fractionated into six eluants on a strong anion exchange column, followed by application to four array chemistries representing cation exchange, anion exchange, metal affinity and hydrophobic surfaces. A total of 144 SELDI-TOF-MS spectra were obtained from each serum sample. RESULTS: The overall profiles of the patient and control samples were consistent and reproducible. However, 30 well-defined protein differences were observed; 15 proteins were elevated and 15 were decreased in patients compared to controls. Serum from 1 patient exhibited novel protein peaks suggesting possible additional changes due to a secondary disease process. CONCLUSION: SELDI-TOF-MS demonstrated consistent serum protein profile differences between patients and controls. Similarity in protein profiles among dialysis patients suggests that patient physiological responses to end-stage renal disease and/or dialysis therapy have a major effect on serum protein profiles.

Adult↗
PubMed1993

Beam profile analysis using GafChromic films.

GafChromic film dosimetry techniques were used to evaluate the beam profiles for each collimator of the Leksell Gamma Knife at the University of Kentucky Medical Center. At the conclusion of acceptance testing, representatives from Leksell exposed conventional films for beam profile processing and analysis in Sweden. At the same time, an inhouse technique using GafChromic films was utilized in the analysis of the beam profiles. GafChromic films were irradiated to 100 Gray to provide data in each of the three planes for each collimator size. The films were analyzed using a scanning helium-neon laser densitometer with a small aperture of 5-10 microns. The digitized density profiles were curve-fitted using a PC plotting algorithm. The curve-fitted density profiles were converted to relative dose using a standard calibration curve determined with a conventional cobalt-60 teletherapy beam. The results are in excellent agreement with the conventional film analysis reported by Leksell. The GafChromic method has proven to be an accurate and rapid method of analysis and could be easily incorporated into a quality assurance program.

Calibration↗
PubMed1997

Influence of gender on the correlation between plasma growth hormone profiles and urinary growth hormone excretion.

A lot of interest has been directed towards the measurement of urinary growth hormone (GH) excretion instead of plasma GH profiles or provocation tests. We investigated the factors influencing the relationship between 24- and 3-hour plasma GH profiles and urinary GH excretion in a cohort of 113 pediatric patients with growth disorders and healthy volunteers. Plasma and urinary GH were measured by polyclonal immunoassays differing in cross-reactivity with 20 kD GH (100 versus 46%), but not with 22-kD, dimer, deamidated and pituitary GH. In the 24-hour urine samples, only urinary GH excretion expressed as nanograms per 24 h correlated with plasma GH parameters, whereas the correlations for short-term samples were strongest if urinary GH excretion was expressed as nanograms per gram creatinine (r = 0.70-79, p < 0.00005-0.0001). In short-term samples urinary GH excretion depends on urinary volume and should thus be expressed in nanograms per gram creatinine, whereas 24-hour samples correlate best when urinary GH is expressed as nanograms per period. We found a significant sex difference (p < 0.02) in the correlation between 24-hour plasma GH profiles and urinary GH excretion with strong correlations in the female group (r = 0.63-0.78, p < 0.00005-0.0002) and a lack of correlation in the male group. The sex difference in the correlations between serum and urinary GH may reflect sex differences in GH profiles and metabolism, with urinary GH better reflecting the basal and slowly clearing portion of plasma GH than spontaneous GH peaks. The difference in cross-reactivities of molecular GH forms in polyclonal assays may have an impact on the correlation between plasma and urinary GH. Thus, the diagnostic value of urinary GH measurement as compared to serum GH profiles needs to be further evaluated.

Adolescent↗
PubMed1996

Action profiles of predictors of death and survival time in stage I malignant melanoma.

BACKGROUND: Many studies have been performed to identify prognostic factors of malignant melanoma using multivariate regression models. In these models, it is generally assumed that quantitative predictors such as age or tumor thickness enter linearly into the model, or they are categorized. OBJECTIVE: The purpose of the present study is to investigate possible curvature (nonlinearity) of predictors of 'death from MM within 5 years after diagnosis' and 'survival time after diagnosis' avoiding the known shortcomings of categorizing predictors. METHODS: Our analyses are based on data of 677 patients with stage I melanoma of the skin collected at the Cancer Registry of the Canton of Zurich. In order to study non-linearity of predictors, we use 'generalized additive models' (GAM): in a GAM the usual prognostic index is replaced in an optimal way by a more flexible form where the individual linear terms are replaced by possibly curved functions of the predictors. Plotting the corresponding curves (the 'action profiles') allows one to visualize easily the shape by which predictors 'act' over the whole range of values. RESULTS: Essentially the same results emerged when studying 'death from melanoma' and 'survival time in melanoma': age and tumor thickness have a pronounced nonlinear association with both endpoints taking simultaneously into account effects of sex and tumor site. The action profile for age is J or U shaped. The action profile for thickness has a 'two-phase' pattern. It increases linearly for low thickness values and flattens for higher values. The shape of the action profiles was checked by performing a Monte Carlo simulation ('boot-strapping'). CONCLUSIONS: The best prognosis of melanoma was found within a middle age range while younger and older patients showed a poorer prognosis. In our data, the increase in thickness in the range above 2 mm is of much less clinical relevance than in the range below 2 mm. GAMs may be of great value for clinicians in providing a visualization of the shape by which predictors act and to obtain a better understanding of the complex relationships between predictors and survival. Not considering curvature of action profiles may result in excluding relevant predictors.

Adult↗
PubMedDate not supplied

Methylation profiling of urothelial carcinoma in bladder biopsy and urine.

OBJECTIVE: To test DNA methylation profiling in detection of urothelial carcinoma in urine. STUDY DESIGN: Thirty-three bladder specimens were analyzed for the DNA p16INK4a, RASSF1, APC, GSTP, E-Cad and CyclinD2 genes to determine if there is a difference in gene methylation between benign and malignant cases. Urine samples were analyzed in a feasibility study. Finally, methylation profiles of urine samples were obtained and compared with follow-up biopsy diagnoses. RESULTS: We found methylated genes in 18% benign, 37% urothelial carcinoma in situ and 93% infiltrating urothelial carcinoma cases (p = 0.001). Methylation profiles from the 18 urine samples revealed a significantly higher prevalence of methylated genes in carcinoma cases than benign cases (100% vs. 50%, p = 0.025). We analyzed methylation profiles in 37 cytologically atypical urine samples with malignant or benign diagnosis on surgical follow-up andfound that only APC (55% in malignant vs. 0% in benign, p=0.025) and CyclinD2 were differentially methylated (35% in malignant vs. 0% in benign, p=0.2) while p14ARF, p16INK4a, RASSF1, GSTP and E-Cad had similar methylation profiles. CONCLUSION: These results suggest that methylation of p14ARF, p16INK4a, RASSF1, GSTP and E-Cad genes may not accurately identify carcinoma, but methylated APC and CyclinD2 might be useful biomarkers for urothelial carcinoma in urine.

Aged↗
PubMed2004

Different predictions by the minimum variance and minimum torque-change models on the skewness of movement velocity profiles.

We investigated the differences between two well-known optimization principles for understanding movement planning: the minimum variance (MV) model of Harris and Wolpert (1998) and the minimum torque change (MTC) model of Uno, Kawato, and Suzuki (1989). Both models accurately describe the properties of human reaching movements in ordinary situations (e.g., nearly straight paths and bell-shaped velocity profiles). However, we found that the two models can make very different predictions when external forces are applied or when the movement duration is increased. We considered a second-order linear system for the motor plant that has been used previously to simulate eye movements and single-joint arm movements and were able to derive analytical solutions based on the MV and MTC assumptions. With the linear plant, the MTC model predicts that the movement velocity profile should always be symmetrical, independent of the external forces and movement duration. In contrast, the MV model strongly depends on the movement duration and the system's degree of stability; the latter in turn depends on the total forces. The MV model thus predicts a skewed velocity profile under many circumstances. For example, it predicts that the peak location should be skewed toward the end of the movement when the movement duration is increased in the absence of any elastic force. It also predicts that with appropriate viscous and elastic forces applied to increase system stability, the velocity profile should be skewed toward the beginning of the movement. The velocity profiles predicted by the MV model can even show oscillations when the plant becomes highly oscillatory. Our analytical and simulation results suggest specific experiments for testing the validity of the two models.

Biomechanical Phenomena↗
PubMed1984

Tracheobronchial gland profiles in four segmental airways.

Previously described methods of measuring the amount of submucous gland in the trachea and bronchi have various disadvantages. These have been overcome by a method in which area point counting has been used to obtain a new unit, Vgl mm3/mm2, the volume of gland per unit airway surface area; Vgl has been obtained for the trachea, the main and lobar bronchi, and for successive airway generations down 4 segmental bronchi (the left lingular , the left anterior basal, the right middle medial, and the right anterior basal) from 3 nonsmokers, and presented in profile form. The profiles have a distinctive shape, not previously appreciated, with a rise to a proximal peak and then a striking fall to low Vgl values in the subsegmental bronchi. The shape of the profile is intriguing, but at present the information required to answer the questions it raises is not available. As there were no significant differences between the profiles of the 4 airways in the individual subjects, any one of the 4 airways may be chosen to give a representative profile for an individual subject.

Adult↗
PubMed1997

Which depressed patients will respond to interpersonal psychotherapy? The role of abnormal EEG sleep profiles.

OBJECTIVE: The authors tested the hypothesis that patients whose episodes of major depression evidenced more neurobiological disturbance would be less responsive to psychotherapy. METHOD: The study subjects were outpatients who were given a diagnosis of recurrent major depressive disorder (unipolar or bipolar II), according to the Research Diagnostic Criteria, following an interview with the Schedule for Affective Disorders and Schizophrenia. They were classified into a group with normal sleep profiles (N = 50) and a group with abnormal sleep profiles (N = 41) on the basis of a validated index score derived from three EEG sleep variables monitored for 2 nights: sleep efficiency, REM latency, and REM density. The groups' responses to short-term interpersonal psychotherapy were compared by means of chi-square tests and life table and random effects model analyses. Responses to the addition of pharmacotherapy for subjects who did not respond to interpersonal psychotherapy were also compared. RESULTS: The patients with abnormal sleep profiles had significantly poorer clinical outcomes with respect to symptom ratings, attrition rates, and remission rates than the patients with more normal sleep profiles. Seventy-five percent of the patients who did not respond to interpersonal psychotherapy had remissions during subsequent pharmacotherapy. CONCLUSIONS: These findings help to define further a neurobiological "boundary" that may limit response to psychotherapy in depression. An abnormal sleep profile may reflect a more marked disturbance of CNS arousal that warrants pharmacotherapy.

Adult↗
PubMed2005

Social profile: assessment of validity and reliability with preschool children.

BACKGROUND: The Social Profile evaluates the social participation levels of children in activity groups and is based on the concepts of group social participation, interaction behavioural skills, and process factors. The 7 factors for each of the group levels in the Social Profile are cooperation, norms, roles, communication, activity behaviour, power and attraction. PURPOSE: This study evaluates the validity and reliability of the Social Profile. METHOD: A panel of eleven judges examined the content of the Social Profile and their recommendations were incorporated. Two occupational therapy observers measured group skills in 15 preschool groups of typically developing children. RESULTS: Cluster analysis of the study data indicated distinctions between skill clusters of social participation levels. Factor analysis confirmed these theoretical and clinical field component factors as distinct behaviours. CLINICAL IMPLICATIONS: The Social Profile has the potential to be used with a wide range of children to assess and treat their social skill deficits. Occupational therapy students and clinicians can use the assessment for training and to expand their observational abilities for evaluating social skills.

Child Behavior↗
PubMed1990

Older adults and daily living task profiles.

This paper describes data generated from a comprehensive study in which human factors techniques were applied to the analysis of 25 personal and instrumental activities of daily living (ADLs) performed by 60 older adults (age 55 to 93 years) living in the community. Demand profiles generated from task analysis of video-taped ADLs identify the demands inherent in task activities and the objects and environments associated with them. Examples of four different approaches to examine ADL performance using demand profiles are presented: global descriptions of demands across all ADL tasks, task component profiles, task-specific profiles, and action profiles.

Activities of Daily Living↗
PubMedDate not supplied

Profiles of college students demonstrating learning disabilities with and without giftedness.

The purpose of this study was to analyze the assessment profiles of two groups of adults with learning disabilities. The first group comprised 48 adults (34 men and 14 women) demonstrating giftedness and a learning disability profile (G/LD). The second group of 46 adults (31 men and 15 women) demonstrated a learning disabled profile without giftedness (NG/LD). Both groups of participants were either attending or planning to attend college and sought testing at a university-affiliated learning disabilities center. Participants' mean age was 20 years, and all were White and from middle to upper-middle class backgrounds. Findings indicate that, as a group, the adults demonstrating a G/LD profile tended to be identified later and have more discrepancy among cognitive assessment profile scores than the NG/LD group. Cognitive subtest scores showed significant differences between the groups, but also several areas of weakness evident in both groups regardless of the presence of giftedness. These findings emphasize the importance of identifying the presence of learning disabilities among gifted populations.

Achievement↗