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PubMed2002

Flow spectra from spectral power density calculations for pulsed Doppler.

Range gated pulsed Doppler can be used to make localized velocity measurements within a blood vessel. Both the transducer and the sample volume are of finite size, and this prohibits the measurement of velocity at a point. A spectral flow profile can be created by stepping a sufficiently small sample volume across the lumen of a vessel. However no such set of spectra will correspond directly to the true velocity profile. In this study we developed a systematic theoretical treatment which allows Doppler spectral power density (SPD) functions to be calculated under a very wide range of conditions. Simulated flow spectra were created from sets of these spectra. The model is based on the beam intensity weighted volume method and incorporates, through the idea of a spread function, Guidi's individual flow line spectrum. Our method can be applied for different spread functions; with beam profiles which are uniform, Gaussian or arbitrarily narrow (needle beam); with range gated sample volumes which can be maximal (CW-type) or minimal (PW-type); and for beams which intersect the flow tube axis, or are off centre. Under all conditions we find the spread function parameter k, equal to the ratio of the central Doppler shift to half the bandwidth, plays a key role. After formulating the model analytically, we sought simplifications to allow results to be obtained from simple, practical formulae. Spread and unspread SPD functions are in most cases given as single integrals which contain measurable physical parameters and can be easily evaluated numerically. Model results are presented for flow spectra of parabolic flow, illustrating the interplay between different factors in determining the appearance of spectral flow profiles.

Blood Flow Velocity↗
PubMed2005

A new approach in the prediction of the dissolution behavior of suspended particles by means of their particle size distribution.

Though various attempts have been made in literature to model the particle size distribution of an active pharmaceutical ingredient (API) in function of the required release profile of the pharmaceutical product, so far one has not succeeded to develop a universal approach in the correlation of particle size distribution and in vitro dissolution data. In this publication, a new approach is presented on the use of particle size distribution data in the prediction of the in vitro dissolution profile of a suspension formulation. For this purpose, various theoretical experiments were done simply on paper and based on the Noyes-Whitney [A.A. Noyes, W.R. Whitney, J. Am. Chem. Soc. 19 (1897) 930-934] equation, the normalized dissolution profiles of various imaginary size distributions were calculated. For each size distribution, its weighted mean diameters were then calculated. Based on these theoretical data, a model could be developed which scientifically explains the dissolution profile of a suspension in function of its volume-weighted mean particle size (D[4, 3]). The applicability of this correlation model could experimentally be confirmed by evaluation of laser diffraction and in vitro dissolution data as they were obtained for different batches of a suspension formulation. This new approach in the correlation between particle size and dissolution may be an important analytical tool in the engineering of the particle size distribution of drug substance, and more precisely monitoring the D[4, 3] volume-weighted mean diameter may allow one to model the dissolution profile of a suspension formulation and thereby its in vivo release profile.

Algorithms↗
PubMed2004

CLOE: identification of putative functional relationships among genes by comparison of expression profiles between two species.

BACKGROUND: Public repositories of microarray data contain an incredible amount of information that is potentially relevant to explore functional relationships among genes by meta-analysis of expression profiles. However, the widespread use of this resource by the scientific community is at the moment limited by the limited availability of effective tools of analysis. We here describe CLOE, a simple cDNA microarray data mining strategy based on meta-analysis of datasets from pairs of species. The method consists in ranking EST probes in the datasets of the two species according to the similarity of their expression profiles with that of two EST probes from orthologous genes, and extracting orthologous EST pairs from a given top interval of the ranked lists. The Gene Ontology annotation of the obtained candidate partners is then analyzed for keywords overrepresentation. RESULTS: We demonstrate the capabilities of the approach by testing its predictive power on three proteomically-defined mammalian protein complexes, in comparison with single and multiple species meta-analysis approaches. Our results show that CLOE can find candidate partners for a greater number of genes, if compared to multiple species co-expression analysis, but retains a comparable specificity even when applied to species as close as mouse and human. On the other hand, it is much more specific than single organisms co-expression analysis, strongly reducing the number of potential candidate partners for a given gene of interest. CONCLUSIONS: CLOE represents a simple and effective data mining approach that can be easily used for meta-analysis of cDNA microarray experiments characterized by very heterogeneous coverage. Importantly, it produces for genes of interest an average number of high confidence putative partners that is in the range of standard experimental validation techniques.

Animals↗
PubMed2001

Investigation of the criminal and conditional release profiles of Canadian federal offenders as a function of psychopathy and age.

Using the Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991) diagnostic cut-off score of 30, the complete criminal career and community release profiles of 317 Canadian federal offenders (224 low scorers and 93 scoring within the psychopathic range) were investigated. Adult crimes were coded according to age at commission as well as either violent, nonviolent, or nonsexually violent. Changes in performance following release into the community also were examined. Results indicated that offenders scoring within the psychopathic range consistently committed more violent and nonviolent crimes than their counterparts for about three decades, spanning their late adolescence to their late 40s. Numbers of nonviolent criminal offenses committed by high PCL-R scorers declined considerably after age 30 relative to violent offenses, which declined and then rebounded in the late 30s before a major reduction was evidenced. Throughout adulthood, high PCL-R scorers failed during community release significantly faster than did low scorers. Importantly, from a risk management perspective, the release performance of low PCL-R scorers improved with age, whereas the opposite was seen for high scorers. Further, offenders scoring high on the PCL-R did not show a lower charge to conviction ratio with age, suggesting that they may not have been getting better at manipulating the legal system.

Adult↗
PubMed2006

Plant metabolomics: towards biological function and mechanism.

Metabolite profiling is a fast growing technology and is useful for phenotyping and diagnostic analyses of plants. It is also rapidly becoming a key tool in functional annotation of genes and in the comprehensive understanding of the cellular response to biological conditions. Metabolomics approaches have recently been used to assess the natural variance in metabolite content between individual plants, an approach with great potential for the improvement of the compositional quality of crops. Here, we assess the contribution of metabolite profiling to these areas.

Botany↗
PubMedDate not supplied

Renoprotective effect of small doses of losartan and enalapril in patients with primary glomerulonephritis. Short-term observation.

BACKGROUND: The renin-angiotensin system is thought to be involved in progression of chronic renal diseases of both diabetic and nondiabetic origin. It is confirmed that angiotensin-converting enzyme inhibitors reduce urinary protein excretion (UPE) and attenuate the development of renal injury. The angiotensin II receptor blockers are an alternative class of drugs inhibiting the renin-angiotensin system activity with preliminarily confirmed renoprotective activity. However, there is lack of data concerning renoprotective action of very small doses of these drugs. METHODS: Prospective, randomized, 3-month study of the effects of losartan 25 mg (n = 17) vs. enalapril 10 mg (n = 17) vs. combination of losartan 25 mg and enalapril 10 mg (n = 15) on proteinuria, kidney function and metabolic profile in 51 patients with biopsy proven chronic glomerulonephritis with normal or slightly declined kidney function [creatinine clearance (CRCL) between 36 and 93 ml/min] was performed. Clinical evaluation and laboratory tests were estimated before treatment (basal), during the first week and after 3 months of therapy. RESULTS: Both, monotherpy with losartan and enalapril significantly reduced proteinuria by 25.35 and 45.07%, respectively. There was no significant difference between groups. Combined therapy induced a more remarkable reduction of proteinuria (65.96%) than either of the drugs administered alone. This antiproteinuric effect was significantly more pronounced only in comparison with the losartan group (p = 0.009). Decreasing of blood pressure was most pronounced in the combined group. In all groups, no correlation between fall of UPE and reducing the systolic or diastolic blood pressure was found. Significant decline in CRCL was observed with enalapril treatment just after 1 week of therapy (p = 0.039) and at the end of observation (p = 0.043). CRCL remained stable in losartan-treated subjects. No changes in serum creatinine level, metabolic profile and sodium excretion were observed during therapy in studied groups. CONCLUSIONS: These results indicated that even very small doses of losartan and enalapril reduce proteinuria in patients with primary glomerulonephritis. Combination of these drugs could cause significantly greater antiproteinuric effect than either of the agents in monotherapy. It is likely that the treatment with losartan, compared to enalapril, is associated with less risk of acute fall of glomerular filtration at the beginning of therapy.

Adult↗
PubMed2004

Assessment of quality of life and cognitive function after out-of-hospital cardiac arrest with successful resuscitation.

This prospective cohort study evaluated the impact of the time-related elements of the "chain of survival" on the quality of life of patients, taking their characteristics into account. Between 1995 and 2002, consecutive, out-of-hospital cardiac arrest patients from Amsterdam and the surrounding areas were included in this study. A total of 227 patients (12%) survived to hospital discharge and 174 were definitive survivors who were available for assessment at 6 months. Quality of life was measured with the 136-item Sickness Impact Profile (SIP); cognitive functioning was assessed through the Mini Mental State Examination. SIP profiles were compared with profiles of an open Dutch population of the elderly and patients who experienced a stroke. Time intervals of the chain of survival were calculated from the estimated moment of collapse and related to outcome using regression analysis. The SIP profile of survivors was a little above the reference profile, indicating a slightly poorer quality of life, and below the profile of patients after stroke, indicating a better quality of life. Impaired cognitive function was associated with delay in the start of cardiopulmonary resuscitation (odds ratio 4.3, 95% confidence interval 1.0 to 19). Absence of the need for advanced cardiopulmonary life support was associated with better cognitive functioning (odds ratio 0.3, 95% confidence interval 0.1 to 0.9). Female gender and older age were associated with impaired physical functioning. Trends were found for better outcomes after early access, immediate resuscitation, early defibrillation, and early advanced care.

Advanced Cardiac Life Support↗
PubMed1991

Strengths and weaknesses in the cognitive profile of youngsters with Prader-Willi syndrome.

In this report we present the results of a study of the intellectual functioning and cognitive profile of 26 Prader-Willi syndrome (PWS) patients. The mean IQ score was 62.3 (range 39-96). In 13 patients a significant difference between verbal and performance IQ was found. In 10 of them the performance IQ was higher than the verbal. The results of subtest analysis indicate that cognitive strengths are more visible than cognitive weaknesses. Highest scores were noted especially in the performance scale, i.e. Block Design (9 children) and Coding or Mazes (5 children). Analysis of all available data indicates that PWS patients score better on visual motor discrimination skills than on auditory verbal processing skills. These results are promising for intervention programs and education strategies.

Adolescent↗
PubMed1984

Hepatic messenger ribonucleic acid activity profiles in experimental azotemia in the rat. Relationship to food intake and thyroid function.

We have studied the hepatic messenger RNA (mRNA) activity profile in chronically azotemic rats and sought to determine whether the observed changes could be mediated either by reduced food intake or diminished thyroid function at the tissue level. mRNA activity profiles were produced by two-dimensional gel electrophoretic separation of radioactively labeled products of an in vitro reticulocyte lysate system which had been programmed by hepatic RNA. Of the approximately 240 translational products identified in this system, seven sequences were consistently altered in azotemia. In pair-fed animals six of these also decreased, but the alterations in three were depressed to a significantly lesser extent in the pair-fed group. Moreover, analysis of covariance suggested that food intake could account for the differences in only one sequence. The possibility that the mRNA activity profile in azotemia could represent the effects of diminished thyroid function was minimized by the finding that the reductions in plasma thyroxine (T4) and triiodothyronine (T3) levels observed were due largely to reduced plasma protein binding, with maintenance of the mean free T4 and free T3 concentrations within the normal range. The changes in only one mRNA sequence could be related to free T3 levels alone. Our findings, therefore, indicate that although diminished food intake and reduced thyroid function may contribute to some of the observed changes in the mRNA activity profiles, the bulk of alterations in azotemia appear to be mediated by other mechanisms. The striking overlap between the sequences affected by azotemia and pair-feeding raises the speculation that altered gene expression in azotemia may reflect an impaired hepatic response at the pretranslational level to metabolic signals associated with food intake.

Animals↗
PubMed2026

Genome-Wide Analysis of the PYL Gene Family and Its Expression Dynamics in Response to Abscisic Acid in Tomato.

The plant hormone abscisic acid (ABA) plays a crucial role throughout the plant life cycle and in adaptive responses to environmental stresses. The pyrabactin resistance 1-like (PYR/PYL/RCAR) proteins act as key regulators in the ABA signal transduction pathway by functioning as direct receptors for ABA. Although PYL genes have been identified in a variety of plant species, their evolutionary and structural characteristics in tomatoes (Solanum lycopersicum) remain elusive. To address this gap, we identified nine SlPYL genes, which were classified into three subfamilies: I (two genes), II (three genes), and III (four genes), and their encoded proteins were predicted to be primarily localized in the cytosol and chloroplast. Structural analysis revealed diverse exon-intron organizations along with five conserved motifs. All identified SlPYLs contained the START domain (PF10604), validating their identity as actual PYL proteins. Prediction of cis-acting regulatory elements in SlPYL's promoter regions was found to be associated with light responsiveness, hormone signaling, stress responses, and plant growth and development. Prediction of post-translational modification sites indicated that SlPYLs are predominantly phosphorylated and acetylated at serine and lysine residues, respectively. Tertiary structure modeling demonstrated conserved three-dimensional architectures among SlPYL proteins, supporting their functional conservation. Expression profiling revealed that specific SlPYL genes exhibit distinct expression patterns across different tissues (root, leaf, and bud) following ABA treatment, indicating functional diversification. Considering the well-established negative correlation between ABA accumulation and bud outgrowth, the ABA-induced differential expression (3~5-fold) of some SlPYL genes (SlPYL3, SlPYL4, SlPYL7, and SlPYL8), particularly in bud tissues after 24 hpt, suggests a potential role in ABA-mediated suppression of bud outgrowth. However, these functional inferences are primarily based on genome-wide computational analyses and expression profiling and therefore require further experimental validation.

Solanum lycopersicum↗
PubMed1995

Local moves: an efficient algorithm for simulation of protein folding.

We have enhanced genetic algorithms and Monte Carlo methods for simulation of protein folding by introducing "local moves" in dihedral space. A local move consists of changes in backbone dihedral angles in a sequential window while the positions of all atoms outside the window remain unchanged. We find three advantages of local moves: (1) For some energy functions, protein conformations of lower energy are found; (2) these low energy conformations are found in fewer steps; and (3) the simulations are less sensitive to the details of the annealing protocol. To distinguish the effectiveness of local move algorithm from the complexity of the energy function, we have used several different energy functions. These energy functions include the Profile score (Bowie et al., Science 253:164-170, 1991), the knowledge-based energy function used by Bowie and Eisenberg 1994 (Proc. Natl. Acad. Sci. U.S.A. 91:4434-4440, 1994), two energy terms developed as suggested by Sippl and coworkers (Hendlich et al., J. Mol. Biol. 216:167-180, 1990), and AMBER (Weiner and Kollman, J. Comp. Chem. 2:287-303, 1981). Besides these energy functions we have used three energy functions that include knowledge of the native structures: the RMSD from the native structure, the distance matrix error, and an energy term based on the distance between different residue types called DBIN. In some of these simulations the main advantage of local moves is the reduced dependence on the details of the annealing schedule. In other simulations, local moves are superior to other algorithms as structures with lower energy are found.

Algorithms↗
PubMed2004

Bowel function and bother after treatment for early stage prostate cancer: a longitudinal quality of life analysis from CaPSURE.

PURPOSE: We measured bowel function and bowel bother longitudinally the first 2 years after treatment for early stage prostate cancer. MATERIALS AND METHODS: We studied bowel function and bother in 1,584 men recently diagnosed with early stage prostate cancer and followed for 2 years after radical prostatectomy, external beam radiation or brachytherapy. Principal outcomes were assessed with the UCLA Prostate Cancer Index, a validated instrument that includes these 2 domains. Multivariate analyses were conducted to ascertain significant predictors of bowel function and bother. Subjects were drawn from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE, TAP Pharmaceutical Products, Inc., Lake Forest, Illinois), a national, longitudinal registry of men with prostate cancer. RESULTS: Men treated with external beam radiation or brachytherapy suffered worse bowel function and were more bothered by it than men treated surgically. After an initial period of posttreatment impairment, all 3 groups demonstrated improvement with time in both domains, although bowel bother persisted longer in men treated with external beam radiation. Surgery patients reached a steady state by 3 months, while those treated with external beam radiation or brachytherapy continued to improve for more than a year after treatment. Older men were more bothered by bowel dysfunction than younger men. Ethnicity, comorbidity and education did not affect either bowel function or bother. CONCLUSIONS: Patients undergoing surgery, external beam radiation or brachytherapy have different longitudinal profiles of bowel function and bother during the first 2 years after treatment. Bowel function and bother are worse after external beam radiation but they are also impaired after brachytherapy. Men choosing surgery experience transient impairment in the bowel domains. This information may be useful to patients making treatment decisions for early stage prostate cancer.

Adenocarcinoma↗
PubMedDate not supplied

The new injury severity score: better prediction of functional recovery after musculoskeletal injury.

OBJECTIVES: Injury Severity Score (ISS) is the most widely used method of assessing severity of injury in blunt trauma. It has been recognized that, by only allowing the score to consider the worst injury for each body system, ISS underestimates the problems of multiple musculoskeletal injuries. The New ISS (NISS) allows the three most severe injuries to be scored, irrespective of region affected, and may give better prediction of functional recovery in these patients. METHODS: A prospective cohort study of 200 patients with musculoskeletal injuries, examining the predictive value of ISS and NISS on functional recovery as measured by patient-derived outcome measures (Short Form-36, Sickness Impact Profile, and Musculoskeletal Function Assessment). RESULTS: NISS was greater than ISS in 34 patients (17%). NISS showed closer correlation with total scores and subscores of the outcomes measures than did ISS (Spearman's rho ranked test, P < 0.05). CONCLUSIONS: NISS, a simple modification from ISS, better predicts functional outcomes in survivors of musculoskeletal trauma, and offers an improvement in the assessment of effectiveness of trauma care delivery.

Adolescent↗
PubMed1986

Predicting the performance of daily activities of patients with chronic lung disease.

40 men and 60 women between the ages of 40 and 59 yr. of age and having the diagnosis of chronic obstructive lung disease as measured by Fev1 values of less than 70% predicted pulmonary function were administered an outcome measure of functional ability, the Sickness Impact Profile. A prediction equation for functional ability, the variables of sex, socioeconomic status, respiratory impairment, and self-reporting of symptoms for analysis. In the two-variable model socioeconomic status and self-reporting of breathing difficulty contributed to 28% of the total variability in functional ability scores. In the three-variable model, adding the third independent variable of respiratory impairment (Fev1) did not significantly increase the explained variability in the outcome measure.

Activities of Daily Living↗
PubMed1995

Effect of age on testicular function in adult males with sickle cell anemia.

OBJECTIVES: To determine the effect of age on testicular function and fertility profile of adult males with homozygous sickle cell disease. DESIGN: A comparative cross-sectional study. SETTING: A university teaching hospital in Nigeria. PARTICIPANTS: Twenty-two adult males with homozygous sickle cell disease and 20 healthy adult males with normal hemoglobin genotype. MAIN OUTCOME MEASURES: Seminal indexes, serum concentration of reproductive hormones, body mass index (BMI), testicular volume index, and span-height difference of patients with homozygous sickle cell disease and normal subjects were compared. Also significant differences were sought between two age groups among patients and control subjects: those < or = 25 years old and those > 25 years of age. RESULTS: The mean BMI, testicular volume index, serum T concentration, and indexes of semen quality of the patients with homozygous sickle cell disease were significantly lower than the values for the control subjects. In contrast, there was no significant difference in the mean concentration of FSH, LH, PRL, and mean span-height difference between both groups. Also, although no significant age-related effect on serum T concentration, testicular volume index, and sperm density was found in the subjects 18 to 40 years of age with normal hemoglobin genotype, patients > 25 years old with homozygous sickle cell disease had significantly higher mean serum T concentration and mean testicular volume index than those < or = 25 years old; their sperm density was also substantially higher. CONCLUSION: Fertility is impaired in adult males with homozygous sickle cell disease probably as a result of abnormal hypothalamic or pituitary function. There is a significant amelioration of the hypogonadism, abnormal sexual function, and poor semen profile with increasing age.

Adolescent↗
PubMed2005

Stability and change of emotional functioning in late life: modelling of vulnerability profiles.

BACKGROUND AND AIMS: The present study investigated stability and change in emotional well-being in a prospective study of a large sample of community-dwelling older adults (> or = 55 years). Emotional functioning was conceptualized according to the tripartite model distinguishing three aspects: general negative affect (NA), depression, and anxiety. The study tested models for the decline of mental health in late life based on the diathesis-stress model. In previous studies, support has been found for the diathesis-stress model (for an overview, see [Goldberg, D.P., Huxley, P., 1992. Common mental disorders: a biosocial model. Routledge, London; Zuckerman, M., 1999. Vulnerability to psychopathology. American Psychological Association, Washington, DC.]). The predictive ability of vulnerability factors (the personality characteristics mastery and neuroticism) and stressful life events and their interaction was tested for an increase in general negative affect, decreased positive affect (PA), and increased anxiety. More specifically, we tested the hypothesis that loss leads to decreased positive affect in subjects with low mastery, whereas threat leads to anxiety in subjects with high neuroticism. METHODS: Data from the Longitudinal Aging Study Amsterdam (LASA) were used. LASA is a longitudinal study in a large representative sample of adults aged 55 to 85 (N=1837). Self-report data on depression, anxiety, and negative affect were collected from adults over a 6-year period in three waves. The data were analyzed using multilevel analysis. RESULTS: The findings revealed an association between low mastery, high neuroticism, and an increase in negative affect, lack of positive affect, and anxiety. Furthermore, high mastery protected against the negative impact of loss events, but neuroticism did not augment the negative impact of threat events on emotional health. CONCLUSION: Partial support was found for a diathesis-stress model of change in emotional functioning in late life. Furthermore, support was found for distinguishing between symptoms of negative affect, depression, and anxiety.

Affect↗
PubMed2004

Novel scoring function for modeling structures of oligomers of transmembrane alpha-helices.

Specific non-covalent interactions between transmembrane (TM) alpha-helices are important in a variety of biological processes. Experimental and computational studies have shown that van der Waals interactions play an important role in the tight packing between TM alpha-helices, although polar interactions can also be important in some instances. Based on the assumption that van der Waals interaction alone is sufficient for a meso-scale (residue-scale) description of the interaction between TM alpha-helices, we have designed a novel residue-scale scoring function for modeling structures of oligomers of TM alpha-helices. We first calculated atomistic van der Waals interaction energies between two amino acids, X and Y, of a pair of parallel alpha-helices, glycine-X-glycine and glycine-Y-glycine and compiled them according to three variables, the distance between the two C(alpha) atoms and the rotational angles of X and Y about their helical axes. Upon averaging over the rotational angles, we obtained one-dimensional interaction energy profiles that are functions of the distance between C(alpha) atoms only. Each of the interaction energy profiles was fitted with a generic fitting function of the distance between C(alpha) atoms, yielding analytical scoring functions for all possible amino acid pairs. For glycophorin A, neu/erbB-2, and phospholamban, lowest-energy conformations obtained through exhaustive scanning of the entire conformational space using the scoring functions were compatible with available experimental data.

Amino Acid Sequence↗
PubMed2005

Profiling of resource use variation among six diseases treated at 82 Japanese special functioning hospitals, based on administrative data.

BACKGROUND: Profiling treatment in Japanese hospitals has rarely been conducted systematically with an administrative database. The study aims to present descriptive statistics of medical profiling and to examine the sources of variation in resource used for six common diseases. METHODS: Administrative records for 266,677 patients were analyzed to examine variation in length of stay (LOS) and total charge (TC) by hierarchical multiple linear regression for cases of ischemic stroke, ischemic heart disease (IHD), great vessel disease (GVD), respiratory neoplasm, gastric neoplasm and colonic neoplasm. RESULTS: Average LOS and TC increased with disease severity and invasiveness of surgical procedure. The coefficient of determination of the full model was highest for LOS in IHD (0.432), and for TC that was highest in GVD (0.702). Among various variable sets examined, surgical procedures explained largest variance in resource use. CONCLUSION: With a standardized database derived from claims data, wide audience of stakeholders in Japanese healthcare will be able to access the profiling of practice or disease variation concerned.

Aged↗