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Results for “Model explainability”

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At least 1,243 records · Page 69Linked to original sources
PubMed2004

Clinical and nutritional correlates of C-reactive protein in type 2 diabetic nephropathy.

BACKGROUND: Patients with diabetic nephropathy are at elevated cardiovascular risk. C-reactive protein (CRP) has been used to successfully predict cardiovascular events. OBJECTIVE: We identified clinical and biochemical characteristics that correlate with CRP levels in diabetic nephropathy patients. DESIGN: Baseline data obtained from 722 patients in the Irbesartan Diabetic Nephropathy Trial included age, sex, body mass index (BMI), systolic blood pressure (BP), serum creatinine, plasma low- and high-density cholesterol, triacylglycerol, serum albumin, hemoglobin A1C, 24h urinary protein excretion, plasma total homocysteine (tHcy), folate, B12, pyridoxal 5'-phosphate (PLP, active form of Vitamin B(6)), and plasma CRP levels. RESULTS: In univariate analyses CRP was positively associated with female sex (r=0.08; P=0.04), BMI (r=0.34; P<0.01), serum creatinine (r=0.21; P<0.01), hemoglobin A1C (r=0.08; 0.04), and inversely associated with PLP (r=-0.17; P<0.01) and folate (r=-0.09; P=0.02). A stepwise multiple regression model found CRP directly correlated with BMI (P<0.01) and serum creatinine (P<0.01), and inversely correlated with PLP (P<0.01). The final model explained 16% of the total variance of CRP. CONCLUSIONS: These results extend previous findings of an inverse relationship between Vitamin B(6) and CRP. The lack of association between CRP and certain established or emerging cardiovascular risk factors offers novel information regarding cardiovascular risk in this population.

Adult↗
PubMed2005

Time course of postnatal motor development in ferrets: ontogenetic and comparative perspectives.

We assess relative time courses of motor development in ferrets and rats and evaluate ferrets as experimental animals for studies of motor development. Motor behaviour of ferret pups was characterized in daily sessions from postnatal day (P) 2 to P63. Observations concerning rotational locomotion ('pivoting'), crawling, walking, upright standing ('rearing') and walking on a narrow path; righting on a surface, in mid-air and on an inclined plane ('geotaxis') were quantified in detail and compared with published data on rat motor development. Besides providing a comprehensive characterization of ferret motor development, our results demonstrate that relative time courses of emergence of motor skills in ferrets and rats are highly similar despite substantially different duration of postnatal periods. The relationship between species was determined by linear regression analysis of an x-y-plot of postnatal ages (y: ferret days; x: rat days) corresponding to given levels of performance of specific skills. The model equation y = 2.46x-4.18 represents the conversion between time courses of rat and ferret motor development. Remarkably, the model explained 81% of data variance (r2 = 0.81) and should hence be useful for translation of motor developmental data between ferret and rat and for comparisons between motor and other functions in ferrets. The highly conserved relative time course also has more general implications for the understanding of comparative aspects of development. In addition, the high reproducibility of data within the present study underscores the suitability of the ferret as an experimental animal for studies of motor development.

Aging↗
PubMed2006

Dopamine and cognitive control: the influence of spontaneous eyeblink rate, DRD4 exon III polymorphism and gender on flexibility in set-shifting.

Converging evidence suggests a modulatory role of dopamine in cognitive control. We investigated the influence of two correlates of dopaminergic activity, the spontaneous eyeblink rate and the DRD4 exon III polymorphism, and the potential impact of gender on flexibility in an attentional set-shifting paradigm. The objective of the study was to confirm previous findings of an association between high eyeblink rates and increased cognitive flexibility. These findings were replicated in 87 healthy volunteers this time using a continuous variable for eyeblink rates instead of a dichotomized variable. The interaction between eyeblink rate and DRD4 found in the previous study was lower and failed significance. Analysis of the collapsed sample of n=150 revealed a main effect of gender and an interaction of gender and eyeblink rate on cognitive control. The complete prediction model explained 26% of the total variance. These data suggest that (1) the eyeblink rate is a reliable predictor of dopamine-mediated flexibility of cognitive control and (2) it is useful to include gender as predictor in future studies of dopaminergic modulation of cognitive control.

Adolescent↗
PubMed2004

Social reinforcement of somatic versus psychological description of depressive events.

The cultural construction of illness model explains the clinical observation that psychological correlates of depression such as sadness and worthlessness are frequently reported in Western cultures, whereas somatic or vegetative complaints are often associated with depression in non-Western cultures. This study employed Portnoy and Salzinger's (J. Gen. Psychol. 70 (1964) 311) verbal conditioning paradigm to determine whether social contingencies, in the form of verbal and non-verbal reinforcement contingent upon verbal responses, affect the reporting of experiences related to depressive events. Using an ABA design, this experimental study (N=36) demonstrated that one's reporting of experiences of hypothetical depressive events, via psychological, somatic, or neutral verbal response classes, can be conditioned by verbal and non-verbal positive social reinforcement, and therefore socially constructed through environmental contingencies. This suggests one pathway by which culture can shape symptom presentation. Implications for clinical interviewing and behavioral assessment, especially in the cross-cultural context, are discussed.

Adolescent↗
PubMed2005

Manifestation, mechanisms and mysteries of gene amplifications.

Gene amplifications are essential features of advanced cancers and have prognostic as well as therapeutic significance in clinical cancer treatment. Models explaining the amplification process, such as breakage-fusion-bridge cycle and excision and unequal segregation of extrachromosomal DNA fragments, predict that independent DNA double-stranded breaks must occur to induce amplification formation. Many cellular, tissue and environmental factors induce DNA damage and amplifications. Also labile DNA sequence features like fragile sites facilitate amplifications. Although, databases and data mining tools of various genomic attributes are already available, extra-large scale systems biology endeavors to decipher dynamics, interactions and dependencies between different factors contributing to amplification process fail, because current databases of DNA copy number aberrations and fragile sites comprise conventional cytogenetics results obtained at far too coarse chromosome band resolution. Array comparative genomic hybridization (aCGH) enables genome-wide gene copy number measurements and amplification detection at molecular genetic resolution. Similarly, cloning and sequencing of fragile sites produce mapping information of vastly improved resolution. In conclusion, databases of aCGH and sequenced fragile sites are needed to resolve the mechanisms of gene amplifications in systems biology configuration.

Chromosome Aberrations↗
PubMed2006

Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements.

INTRODUCTION: The primary objective of this study was to determine whether variability in warfarin dose requirements is determined by common polymorphisms in genes whose products are involved in the pharmacodynamics and pharmacokinetics of warfarin, namely, the coagulation factors, vitamin K epoxide reductase complex subunit 1 (VKORC1), and cytochrome P450 (CYP) 2C9. METHODS: Patients (N = 350) receiving stable doses of warfarin at 3 consecutive visits were enrolled, and a deoxyribonucleic acid sample was collected. Samples were genotyped for polymorphisms in the factor II, factor VII, factor X, VKORC1, and CYP2C9 genes. A stepwise linear regression analysis was used to determine the independent effects of genetic and nongenetic factors on mean warfarin dose requirements. RESULTS: Variables associated with lower warfarin dose requirements were VKORC1 3673 AA genotype (P < .0001), VKORC1 3673 GA genotype (P < .0001), 1 variant CYP2C9 allele (P < .0001), 2 variant CYP2C9 alleles (P = .0004), increasing age (P = .0005), concomitant CYP2C9 inhibitors (P = .0005), and goal international normalized ratio (P = .01). Variables associated with higher warfarin dose requirements were weight (P < .0001), current smoker status (P = .0009), mean international normalized ratio (P = .001), concomitant CYP2C9 inducers (P = .006), factor X insertion/deletion genotype (P = .01), factor X insertion/insertion genotype (P = .04), factor VII deletion/deletion genotype (P = .04), and calculated vitamin K intake (P = .05). The linear regression model explained 51.4% of the variability in warfarin dose requirements. CONCLUSION: Polymorphisms in warfarin drug target and metabolizing enzyme genes, in addition to nongenetic factors, were important determinants of warfarin dose requirements.

Adult↗
PubMed2006

Emil du Bois-Reymond vs Ludimar Hermann.

This essay recounts a controversy between a pioneer electrophysiologist, Emil du Bois-Reymond (1818-1896), and his student, Ludimar Hermann (1838-1914). Du Bois-Reymond proposed a molecular explanation for the slight electrical currents that he detected in frog muscles and nerves. Hermann argued that du Bois-Reymond's 'resting currents' were an artifact of injury to living tissue. He contested du Bois-Reymond's molecular model, explaining his teacher's observations as electricity produced by chemical decomposition. History has painted Hermann as the wrong party in this dispute. I seek to set the record straight.

Electrophysiology↗
PubMed2004

Molecular genetic and physiologic background of the growth hormone-IGF-I axis in relation to breeding for growth rate and leanness in pigs.

The GH-IGF-I axis is of major importance for the regulation of body growth and composition, and cellular proliferation and differentiation processes. Selective breeding aiming to improve growth rate and/or body composition is accompanied by changes of the GH-IGF-I axis. Research aiming to elucidate the genetic and physiologic mechanism(s) underlying these changes may best use single-trait selection lines. Two such pig selection lines, one for growth rate and one for high lean content, were used in experiments to investigate the mechanisms of the GH-IGF-I axis change during selection. This contribution reviews the selection-related changes in the GH-IGF-I axis as the consequences of selection for whole body growth rate or body composition and effects on local tissue growth rate. A model explaining the observed effects and consequences for the pressure on the physiology is presented. In short, selection related demand for GH induces GH synthesis until a limit is reached. After that the pulsatile GH plasma profile changes, which may also affect expression profiles of genes regulating body composition.

Animal Husbandry↗
PubMed2004

Are changes in fear-avoidance beliefs, catastrophizing, and appraisals of control, predictive of changes in chronic low back pain and disability?

Interventions for chronic low back pain (CLBP) often attempt to modify patients' levels of catastrophizing, their fear-avoidance beliefs, and their appraisals of control. Presumably, these interventions are based on the notion that changes in these cognitive factors are related to changes in measures of adjustment. The aim of the present study was to explore whether changes on these cognitive factors were related to changes in CLBP and disability. Fifty-four CLBP patients completed a series of self-report measures prior to beginning a cognitive-behavioral based intervention and again upon discharge. Change scores (post-treatment score minus pre-treatment score) were calculated for each of the self-report measures. The study found that changes in the cognitive factors were not significantly associated with changes in pain intensity. In contrast, reductions in fear-avoidance beliefs about work and physical activity, as well as increased perceptions of control over pain were uniquely related to reductions in disability, even after controlling for reductions in pain intensity, age and sex. The final model explained 71% of the variance in reductions in disability.

Activities of Daily Living↗
PubMed2005

Tracheal width and left double-lumen tube size: a formula to estimate left-bronchial width.

STUDY OBJECTIVE: To determine which patient parameters best predict left bronchial width (LBW) when selecting the correct size double-lumen tube (DLT). If LBW is known, a DLT that will fit that bronchus can be chosen. DESIGN: Prospective study. SETTING: University medical center. PATIENTS: Three hundred twenty-one consecutive patients scheduled for thoracic surgery and for whom there was a chest radiograph and for whom tracheal width (TW) and LBW could be measured. MEASUREMENTS: Tracheal width and LBW were directly measured from the chest radiograph. Patient demographic data were recorded and then analyzed to see which factor(s) best predicted LBW. Parameters often used for DLT selection (age, sex, height, and weight) as well as TW were compared by univariate and multivariate statistical analysis to see which factor(s) most accurately predicted LBW. MAIN RESULTS: There were weak but significant correlations between age and height and LBW in men, and height and LBW in women. Multivariate statistical analysis showed that, for both men and women, TW was the best predictor of LBW. Sex, height, and weight did not improve predictability over TW alone. The equation that best predicts LBW for both sexes is: LBWmm = (0.50)(TWmm) + 3.7 mm. This model explains 46% of the variance in LBW. As structures measured from a chest radiograph are magnified by 10%, the formula to predict LBW, which normalizes for this magnification factor, is: LBWmm = (0.45)(TWmm(CXR)) + 3.3 mm. CONCLUSIONS: Direct airway measurement is the most accurate way to select an appropriate DLT. However, when direct measurement of LBW cannot be performed, estimating LBW from TW is a better predictor of LBW than either sex, height, or weight.

Adult↗
PubMed2003

Tuning the heterogeneous early folding dynamics of phosphoglycerate kinase.

We recently reported stretched kinetics during the formation of a collapsed, long-lived intermediate state of the large two-domain enzyme phosphoglycerate kinase (PGK). It was postulated that intrinsic roughness of the energy landscape on the way downhill to the intermediate causes the lack of a single time-scale. Here, we investigate several alternative explanations for stretched refolding dynamics in more detail: tyrosine fluorescence, multiple tryptophan probes, and rate differences between independently folding domains. To this end, we systematically simplify PGK in several steps from the full protein with two tryptophan residues and all tyrosine residues probed, to a single domain with only one tryptophan residue and no tyrosine residue probed. The kinetics in the 10 micros to 10 ms range are revealed by laser-induced temperature-jump relaxation experiments. The isolated N-terminal domain forms an intermediate by nearly single-exponential kinetics, but the isolated C-terminal domain shows strongly non-exponential kinetics. Thus, domain interaction and a cis-proline residue between the two domains are ruled out as the sole contributors to heterogeneity during the earliest folding dynamics of the C-terminal domain. We apply two limiting models for the roughness of the energy landscape. A sequential three-state model lumps all the roughness into a single trap. The "strange kinetics" model with logarithmic oscillations developed by Klafter and co-workers distributes the roughness over a larger number of states. Both models explain our data about equally well, but the coincidental values of rate constants in all of our double-exponential fits, and the absence of a spectroscopic signature distinct from the endpoints of the folding process favors more roughness than can be explained by just a single trap.

Circular Dichroism↗
PubMed2006

Opioid use and survival at the end of life: a survey of a hospice population.

Concern that opioids hasten death may be among the reasons that pain is treated inadequately in populations with advanced illness. Studies that assess the true risks are needed. To determine whether survival after last opioid dose change is associated with opioid dosing characteristics and other factors, data from the National Hospice Outcomes Project, a large prospective cohort study involving 13 U.S. hospice programs, were analyzed. Of 1,306 patients, 725 received opioids and underwent at least one dose change before death. Subsamples based on maximum opioid dose compared patients receiving usual doses with those receiving high-dose therapy. Spearman rank correlations examined bivariate associations between survival after final dose change and other variables, including dose in morphine equivalent mg and percentage dose increase. Multivariate least squares regression analyses determined associations between survival and other variables, including those significant in bivariate analyses. The mean+/-SD number of days between final dose change and death was 12.46+/-23.11. Multivariate models demonstrated a significant association between shorter survival and higher opioid dose, a cancer diagnosis, unresponsiveness, and pain of <5 on a 0-10 scale, but none of these models explained >10% of the variance in time till death. Analyses of subsamples did not reveal additional effects of dose. This analysis revealed that opioid dosing was associated with time till death, but this factor would explain very little of the variation in survival. In a hospice population, survival is influenced by complex factors, many of which may not be measurable. Based on these findings, concern about hastening death does not justify withholding opioid therapy.

Aged↗
PubMed2005

The prediction of safe lifting behavior: an application of the theory of planned behavior.

PROBLEM: Injuries resulting from lifting are costly, and create significant pain and discomfort. While engineering controls are the most effective means of reducing risks, most organizations continue to rely on manual lifting techniques. The problem, however, is that the use of safe-lifting techniques is inconsistent and managers have a difficult time motivating use of these techniques. Consequently, it is important to understand the factors driving safe-lifting behaviors. METHODS: This study used a survey to apply the theory of planned behavior (Ajzen., I., 1991. The theory of planned behavior. Organization Behavior and Human Processes, 50, 179-211) to safe-lifting among 136 materials management employees at a heavy manufacturing organization. Structural equation modeling and factor analysis were employed to analyze relationships among constructs. RESULTS: Results revealed that perceived behavioral control and intention were the strongest predictors of safe-lifting behavior. Subjective norms, to a lesser degree, were also important influences on intention. Attitudes did not surface as effective direct predictors of safe-lifting behavior, but did affect behavior and intent via mediating factors (subjective norms and perceived behavioral control). Finally, the theory of planned behavior was supported as an effective model explaining safe-lifting behavior, and had potential application for many other safety-related behaviors. IMPACT ON INDUSTRY: Results from this study emphasize the importance of perceived behavioral control as a factor associated with safety-related behavior.

Attitude to Health↗
PubMed2004

Factor analysis of the metabolic syndrome in spinal cord-injured men.

Disturbances of carbohydrate and lipid metabolism in men with spinal cord injury are common, but poorly defined. Clustering of recognized risk factors for obesity and disorders of carbohydrate and lipid metabolism are characteristic of the metabolic syndrome. The purpose of this study was to investigate the presence of metabolic syndrome using modifications of the World Health Organization (WHO) definition and including total physical activity levels (minutes/week), in a group of active males with spinal cord injury who were carefully matched for age, height, and weight with active able-bodied males. Factor analysis is used widely to explore factors of the metabolic syndrome. This technique was used in this study of 20 spinal cord-injured (SCI) men and 20 able-bodied controls, matched for age, height, and weight. Three-factor models, each reflecting a different aspect of the metabolic syndrome, were identified for both study groups. The average communality score for the SCI group was 0.8 and 0.7 for the control group. For the SCI group, factor 1 reflected an interaction between adiposity measures, physical activity, and postload insulin and glucose, factor 2 was reflective of dyslipidemia, while factor 3 revealed an interaction between fasting levels of insulin and glucose. In the control group, factor 1 reflected an association between the adiposity measures and physical activity, factor 2 was reflective of postload glycemic control, with factor 3 reflecting an interaction between fasting insulin and dyslipidemia. By summation of the total variance of each factor, the 3-factor models explained 80% and 69% of the variance in the original 9 variables examined in the SCI and control groups, respectively. In summary, while the WHO definition for the metabolic syndrome appears suitable for use in identifying the incidence of this syndrome in SCI men, some modification of anthropometric and lipid measures may be required.

Adipose Tissue↗
PubMed2004

A role for extracellular metallothioneins in CNS injury and repair.

For many years, research focus on metallothioneins, small zinc binding proteins found predominantly within astrocytes in the brain, has centred on their ability to indirectly protect neurons from oxygen free radicals and heavy metal-induced neurotoxicity. However, in recent years it has been demonstrated that these proteins have previously unsuspected roles within the cellular response to brain injury. The aim of this commentary is to provide an overview of the exciting recent experimental evidence from several laboratories including our own suggesting a possible extracellular role for these proteins, and to present a hypothetical model explaining the newly identified function of extracellular metallothioneins in CNS injury and repair.

Animals↗
PubMed2006

Cellular inflammatory responses: novel insights for obesity and insulin resistance.

Type 2 diabetes is rapidly becoming a worldwide epidemic. Obesity and sedentary lifestyle are the main environmental causes for the development of insulin resistance and type 2 diabetes. In the past decade, it has been increasingly recognized that obesity and insulin resistance are associated with chronic, low-grade systemic inflammation. This review will cover the recent advances in this field and provide a working model explaining how cellular inflammatory responses arise to cope with obesity-induced metabolic stresses and how these inflammatory responses underlie insulin resistance.

Adipose Tissue↗
PubMed2005

The evolutionary origin of genetic instability in cancer development.

The standard model of carcinogenesis is currently being questioned. The main controversy concerns genetic instability and has links to fundamental questions in evolutionary biology. This paper aims to clarify the underlying conflict between the linear configuration of the standard model and the non-linear dynamics of Darwinian evolution. It addresses the problem of applying the concept of clonal selection to genetically unstable cells and presents an alternative perspective based on the principles of molecular evolution. This model explains genetic instability in terms of competition between genetic strategies and draws lines to basic aspects of evolutionary biology.

Animals↗