Degree Of Imbalance Research Articles

Molecular Analysis of Alpha Hemoglobin Stabilizing Protein (AHSP) in Caucasian Patients with different Beta-Thalassemia Phenotypes.

Beta-thalassemia is a inherited hemoglobin disorder characterized by absent or reduced synthesis of the b globin chains. The pathophysiology and the severity of b-thalassemias reflect the degree of globin chain imbalance and the excess of free a globin chains that precipitate and cause oxidative damage in red cell precursors inducing their premature destruction in the bone marrow (ineffective erythropoiesis). Although the phenotype of b thalassemias can be modified by inherited factors such as different number of a globin genes or increased fetal hemoglobin production, other mechanisms appear to be involved. Recently, a protein, named alpha hemoglobin stabilizing protein (AHSP), that acts as a molecular chaperone specifically for free a globin chains, preventing their precipitation in red cell precursors, has been identified.To establish whether AHSP might have a role in modifying the clinical outcome of b thalassemias, we have analyzed the AHSP gene in 70 Caucasian b thalassaemic subjects: 26 patients with b°/b° genotype (Thalassaemia Major),24 patients with Thalassemia Intermedia (b°/b+ or b+/b+) and 20 patients with a Thalassaemia Intermedia phenotype but with only one mutation in the b globin gene, a normal a globin genotype and no other causes of anemia. In all the subjects, we have performed Denaturing High-Performance Liquid Chromatography (DHPLC) of the three exons and the direct genomic sequencing of coding and noncoding regions (~ 1.5 kb) of AHSP gene. No mutations able to modify the structure or function of AHSP have been found, however we identified eight single nucleotide polymorphisms (SNPs) spanned along the whole gene that segregate in four different aplotypes. To evaluate a possible relationship between a particular aplotype and b thalassemia severity, the allele frequency of each single aplotype in the tree groups has been established and compared to that of 33 Caucasian normal controls: no statistically significant association has been proved. Even though the loss of AHSP aggravates the b thalassaemia phenotype in mice, in Thalassemic Caucasian population the AHSP apparently doesn't make changes in the clinical severity of b thalassemia confirming the results recently found in Thai population.

Statistical comparison of random allocation methods in cancer clinical trials

The selection of a trial design is an important issue in the planning of clinical trials. One of the most important considerations in trial design is the method of treatment allocation and appropriate analysis plan corresponding to the design. In this article, we conducted computer simulations using the actual data from 2158 rectal cancer patients enrolled in the surgery-alone group from seven randomized controlled trials in Japan to compare the performance of allocation methods, simple randomization, stratified randomization and minimization in relatively small-scale trials (total number of two groups are 50, 100, 150 or 200 patients). The degree of imbalance in prognostic factors between groups was evaluated by changing the allocation probability of minimization from 1.00 to 0.70 by 0.05. The simulation demonstrated that minimization provides the best performance to ensure balance in the number of patients between groups and prognostic factors. Moreover, to achieve the 1 percentile for the p-value of chi-square test around 0.50 with respect to balance in prognostic factors, the allocation probability of minimization was required to be set to 0.95 for 50, 0.80 for 100, 0.75 for 150 and 0.70 for 200 patients. When the sample size was larger, sufficient balance could be achieved even if reducing allocation probability. The simulation using actual data demonstrated that unadjusted tests for the allocation factors resulted in conservative type I errors when dynamic allocation, such as minimization, was used. In contrast, adjusted tests for allocation factors as covariates improved type I errors closer to the nominal significance level and they provided slightly higher power. In conclusion, both the statistical and clinical validity of minimization was demonstrated in our study.

Behavioral evidence for competing motivational drives of nociception and hunger

Homeostasis, an organisms’ tendency to maintain a healthy balance of the physiological state of the body, is necessary for survival. Hunger induces a motivational state to consume food. Recently, pain has been referred to as a homeostatic emotion similar to hunger or thirst in that animals are motivated to respond in a certain way that may increase their chance of survival. Therefore, the purpose of the present experiment was to examine behavior in rodents during two competing homeostatic/motivational drives (i.e., hunger and formalin pain). During the first phase of the formalin test, animals displayed typical responsiveness to the inflammatory condition and completed fewer chains for food reinforcement as compared to the baseline session. However, during the second phase of the formalin test, animals showed decreased nociceptive behavior compared to formalin-injected animals that were not trained in the operant conditioning paradigm. During this phase, the trained animals exhibited maximal responsiveness for food reinforcement. These results demonstrate that the engagement of behaviors reflecting motivational drives to restore homeostasis depends on the intensity or degree of imbalance of the competing drives. More specifically, animals are motivated to attend to one state of imbalance at a time.

Growth index, assessed with Ki-67 and ssDNA labeling, is a significant prognosticator for patients who underwent curative resection for hepatocellular carcinoma

4084 Backgroud: The growth of tumor depends on the degree of imbalance between cell production and cell loss. Knowledge of such biological difference is of importance to understand aggressiveness of the cancer and to the management of cancer patients. This study was conducted to clarify a possible role of the modified prognosticator, Growth Index (GI), in patients who underwent curative resection for hepatocellular carcinoma (HCC). GI (%) was defined as a difference between a Ki-67 labeling index (%) and a single-stranded DNA (ssDNA) labeling index (%). Methods: HCC tissue specimens were obtained from 40 HCC patients (27 men and 13 women, range 45–80 years old) who underwent curative resection between April 1998 and March 2001. Immunohistochemical staining was perfomed using the avidin-biotin-peroxidase-complex method on formalin-fixed paraffin-embedded-tissues. Results: Ki-67 labeling index ranged from 0.20% to 29.10%, and ssDNA labeling index ranged from 0.22% to 4.20%. The GI ranged from -1.90% to 28.65% with a median of 3.73. GI was related with histologic grade (P = 0.014 by Kruskal-Wallis), pathologic T stage (P = 0.026 by Kruskal-Wallis), and intrahepatic metastasis (P = 0.048 by Mann-Whitney). The cumulative survival was poorer in patients with higher GI (≥ 3.73%, a median value) than those with lower GI (P = 0.014 by log-rank test). The univariate analysis demonstrated that GI, histologic grade, pathologic T stage, vascular invasion, intrahepatic metastasis, and age were significant factors affecting survival. The Cox multivariate analysis indicated that GI (P = 0.003) is an independent prognosticator along with intrahepatic metastasis (P = 0.003) and age (P = 0.018). Conclusions: Higher values of GI were significantly associated with histologically aggressive features of HCC, and GI was a significant independent prognosticator in HCC patients after curative resection. Assessing GI is feasible on routine paraffin sections and may provide additional prognostic information in those post-operative patients. No significant financial relationships to disclose.

Growth index, assessed with Ki-67 and ssDNA labeling, is a significant prognosticator for patients who underwent curative resection for hepatocellular carcinoma

4084 Backgroud: The growth of tumor depends on the degree of imbalance between cell production and cell loss. Knowledge of such biological difference is of importance to understand aggressiveness of the cancer and to the management of cancer patients. This study was conducted to clarify a possible role of the modified prognosticator, Growth Index (GI), in patients who underwent curative resection for hepatocellular carcinoma (HCC). GI (%) was defined as a difference between a Ki-67 labeling index (%) and a single-stranded DNA (ssDNA) labeling index (%). Methods: HCC tissue specimens were obtained from 40 HCC patients (27 men and 13 women, range 45–80 years old) who underwent curative resection between April 1998 and March 2001. Immunohistochemical staining was perfomed using the avidin-biotin-peroxidase-complex method on formalin-fixed paraffin-embedded-tissues. Results: Ki-67 labeling index ranged from 0.20% to 29.10%, and ssDNA labeling index ranged from 0.22% to 4.20%. The GI ranged from -1.90% to 28.65% with a median of 3.73. GI was related with histologic grade (P = 0.014 by Kruskal-Wallis), pathologic T stage (P = 0.026 by Kruskal-Wallis), and intrahepatic metastasis (P = 0.048 by Mann-Whitney). The cumulative survival was poorer in patients with higher GI (≥ 3.73%, a median value) than those with lower GI (P = 0.014 by log-rank test). The univariate analysis demonstrated that GI, histologic grade, pathologic T stage, vascular invasion, intrahepatic metastasis, and age were significant factors affecting survival. The Cox multivariate analysis indicated that GI (P = 0.003) is an independent prognosticator along with intrahepatic metastasis (P = 0.003) and age (P = 0.018). Conclusions: Higher values of GI were significantly associated with histologically aggressive features of HCC, and GI was a significant independent prognosticator in HCC patients after curative resection. Assessing GI is feasible on routine paraffin sections and may provide additional prognostic information in those post-operative patients. No significant financial relationships to disclose.

Modeling and simulation of unintended electromagnetic emission from digital circuits

AbstractThis paper presents a summary of a quantitative method for evaluating the EMI generation mechanism of a printed circuit board (PCB). First, mismatch of the degree of imbalance of transmission systems on a PCB is pointed out as a common‐mode generation mechanism of high‐speed signal systems. An EMI prediction method based on two‐dimensional analysis is presented along with its results. Next, with regard to the analysis of EMI generation by resonance of the power supply system in a multilayered PCB, a high‐speed simulation by an analytical method and its further extension are described. Finally, a linear macro model (LECCS model) for the device power supply proposed by the author for EMI analysis is presented. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 87(8): 38–46, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10189

Intestinal microflora in patients with liver cirrhosis

Patients with liver cirrhosis have varying degrees of imbalance of the intestinal flora and probiotics can improve some of the symptoms of gastrointestinal dysfunction in these patients. In the present study, blood ammonia, fecal pH, fecal ammonia, and plasma endotoxin were measured after administration of two kinds of probiotics in order to detect the changes in intestinal flora. Six bacteria and yeast were cultured and the colony forming units were counted. Fifty cirrhotic patients were randomized to receive probiotic capsules containing Bifidobacterium, Lactobacillus acidophilus and Enterococcus, or probiotic capsules containing Bacillus subtilis and Enterococcus faecium for 14 days. Fecal flora, pH and ammonia, blood ammonia (detected by test paper) and plasma endotoxin (detected by LAL test kits) were measured before and after the treatment. Patients with liver cirrhosis had varying degrees of imbalance of the intestinal flora as shown by a decrease in the Bifidobacterium count (10.04 +/- 0.78 vs 9.48 +/- 1.13, P < 0.05). The severity of the imbalance was matched by that of liver dysfunction, with the most serious imbalance observed in Child-Pugh C patients. Both types of probiotic increased the Bifidobacterium count (9.46 +/- 1.09 vs 10.30 +/- 1.11, 9.81 +/- 0.62 vs 10.44 +/- 1.08, respectively, P < 0.05) and reduced the levels of fecal pH and fecal and blood ammonia (P < 0.05). Probiotics containing B. subtilis and E. faecium reduced the level of endotoxin in cirrhotic patients with endotoxemia (0.0876 +/- 0.0117 Eu/mL vs 0.0685 +/- 0.0246 Eu/mL, P < 0.05). Patients with liver cirrhosis have an imbalance of intestinal bacteria flora. Probiotics effectively increased the Bifidobacterium count and reduced the level of fecal pH and fecal and blood ammonia.

Triboelectric Charging Between Polytetrafluoroethylene and Metals

Measurements were obtained on charge exchange processes occurring between small metal ballistic pellets and a polytetrafluoroethylene (PTFE) tube. Lead pellets of 5.5-mm diameter were propelled at a range of speeds through PTFE tubes of different lengths by compressed carbon dioxide. The charge incurred by the pellets and the tube was compared with the charge observed on copper and lead spheres rolled through the tube, driven by gravity. In all experiments, the charge on the moving pellet was measured with a Faraday cup. The experiments determined the effect of pellet speed on the magnitude of the charge accumulated on the pellet and on the PTFE tube. Sectioned shielding on the PTFE tube allowed the determination of surface charge distribution along its length by means of an electrometer. It was observed that the charge also depended on the work functions of the materials involved (lead, copper, PTFE). The charge on the pellets was found to range from +0.5/spl times/10/sup -8/ to +3.0/spl times/10/sup -8/ C, for pellet speeds from 10 to 80 m/spl middot/s/sup -1/. The reproducibility of results is discussed and comment provided on the degree of charge imbalance observed.

Genetic insights into the clinical diversity of beta thalassaemia.

Genetic insights into the clinical diversity of beta thalassaemia.

On the distribution of magnetic null points above the solar photosphere

Many theories predict magnetic energy dissipation at locations, called null points, where the magnetic field vanishes. In several astrophysical contexts, most notably the solar corona, energy is released within a low-β magnetic field anchored to a lower boundary, the photosphere. A general expression is derived for the distribution of magnetic null points in potential magnetic fields anchored to a random, homogeneous distribution of field on the lower boundary. For all such fields the null point density decreases with height and scales with the inverse cube of the field’s characteristic length. For photospheric fields which appear unipolar at the largest scales the nulls are confined to a narrow layer. The results are applied to models of the quiet Sun whose photospheric field consists of discrete sources of mixed polarity. The number of coronal nulls depends on the degree of imbalance between positive and negative sources. Numerical experiments reveal that the greatest column density of null points occurs when ∼20% of the sources are of the minority sign. Were the coronal energy dissipation to occur at magnetic null points this result predicts an observable relationship between flux imbalance and the amplitude and distribution of dissipation.

Effects of spinal cord lesion level upon thermoregulation during exercise in the heat.

This study examined the effects of the level of spinal cord injury upon the thermoregulatory responses of wheelchair athletes during prolonged wheelchair exercise in warm conditions. Eight tetraplegic (TP), 10 high-level paraplegic (HP), and 10 low-level paraplegic (LP) athletes exercised for 60 min at 60% [OV0312]O(2peak) in a warm environment (31.5 +/- 1.7 degrees C, 42.9 +/- 8.0% relative humidity). Skin temperature and aural temperature were monitored. Aural temperature increased gradually during the exercise period by 1.1 +/- 0.3 and 1.4 +/- 0.5 degrees C for the HP and LP groups, with a more marked increase observed for the TP group (2.1 +/- 0.5 degrees C; P < 0.05). Upper-arm skin temperature was higher for the TP when compared with the HP and LP between 30 and 60 min (P < 0.05). Back skin temperature was higher for the TP when compared with the HP and LP between 45 and 60 min (P < 0.05). No differences were noted between groups for the thigh or calf skin temperatures. During recovery, skin temperature remained elevated for the TP group when compared with the HP and LP groups (P < 0.05). Heat storage was greatest for the TP athletes at the end of exercise and remained elevated throughout recovery (P < 0.05). All athletes completed the exercise task even though the gradual increase in aural temperature observed for the HP and LP groups suggests a degree of thermal imbalance. However, this was much less than observed for TP athletes, who demonstrated a much greater imbalance in temperature regulation. Increasing the exercise or environmental strain may result in the thermoregulatory responses of athletes with a spinal cord injury being compromised.

The Effect of Design Imbalance on the Power of the F‐test of a Variance Component in the One‐Way Random Model

AbstractThe ANOVA‐based F‐test used for testing the significance of the random effect variance component is a valid test for an unbalanced one‐way random model. However, it does not have an uniform optimum property. For example, this test is not uniformly most powerful invariant (UMPI). In fact, there is no UMPI test in the unbalanced case (see Khuri, Mathew, and Sinha, 1998).The power of the F‐test depends not only on the design used, but also on the true values of the variance components. As Khuri (1996) noted, we can gain a better insight into the effect of data imbalance on the power of the F‐test using a method for modelling the power in terms of the design parameters and the variance components. In this study, generalized linear modelling (GLM) techniques are used for this purpose. It is shown that GLM, in combination with a method of generating designs with a specified degree of imbalance, is an effective way of studying the behavior of the power of the F‐test in a one‐way random model.

Estimation of nakagami-m fading channel parameters with application to optimized transmitter diversity systems

An optimum power loading algorithm for transmitter diversity systems over correlated and unbalanced Nakagami (1960) paths and its performance evaluation under perfect channel estimate conditions are derived. In addition, various online estimators of the required Nakagami channel parameters for optimized power loading and the comparison of their mean square error via Monte Carlo simulations are presented. Some of these estimators are used to obtain the performance of optimized transmitter diversity systems under imperfect channel estimation (ICE). These numerical results show that the diversity gain of these optimized systems compared with equipower systems increases as the severity of fading decreases and as the degree of branch imbalance increases even under ICE. On the other hand, in weakly correlated and (or) unbalanced branches, optimized transmitter diversity systems offer negligible gain or even losses compared with unoptimized systems because of the ICE.

2697 The unexpected sleep apnea syndrome is highly prevalent and associated with the alteration of the autonomic nervous system activity in a general 65 years old population. The PROOF study

Aim Up to 5% of adults in Western countries are likely to have undiagnosed obstructive sleep apnea syndrome (OSAS). OSAS had be found to be particularly highly prevalent in people older than age 65 years. The identification of OSAS as a risk factor for increased morbidity and mortality is needed in such older population since they should become candidates for treatment. The autonomic nervous system (ANS) activity, a recognized marker of cardiovascular and all cause mortality in a general population, is precociously altered in OSAS: the degree of autonomic imbalance appears correlated with sleep fragmentation, inspiratory efforts and hypoxia. Methods We thus evaluated in a large cohort (n=1011) of 65+-0.4 years old men (40%) and women (60%) free of cardiovascular of cerebrovascular event or of diagnoses Sleep Related Breathing Disorders, the prevalence of unexpected OSAS and its relationship with ambulatory blood pressure, spontaneous cardiac baroflex sensitivity and basal cardiac autonomic activity.

A Combined Invariant Test for a Null Variance Ratio

AbstractThis paper investigates the properties of a test that combines the Wald and LMPI (locally most powerful invariant) tests of variance components in unbalanced mixed models. The combined test statistic is easily computed and its null distribution may be approximated by a central F distribution with the degrees of freedom of the numerator adjusted in accordance with the degree of imbalance of the design. Numerical methods are used to show that the approximation is accurate over a wide range of conditions and that the efficiency of the combined test, relative to the power envelope, is satisfactorily high overall.

CLASSIFICATION OF TYPES OF SOCIETAL CONFLICTS AND CHARACTERIZATION OF THEIR RESOLUTION PROCESSES BASED ON DEONTIC LOGIC

Focusing on the interaction among members' attitudes toward issues of common concern and members' expectance toward other members' attitudes, type classification of societal conflicts and their degree of strength are clarified. For the purpose, a vigorous theoretical framework for the examination of interrelationships among various normative concepts such as obligation, permission, prohibition, etc. is introduced, on the basis of the general theory on norms, deontic logic. By presuming several plausible laws on the way of the resolution of these conflicts and by introducing a two-dimensional representation of the conflicts with one axis representing the degree of imbalance and the other axis representing the cohesiveness of systems, a characterization method of conflict resolution processes is obtained, through which prediction and analysis of actual resolution processes can be done.

An intelligent support system for the analysis of power system transients

Electromagnetic transient programs such as EMTP are extensively used for simulating fast transient effects in electric power systems. However, these programs are not easy to use for the following two reasons. 1. All of them require a high level of technical expertise to apply them properly. 2. Most of them are not user friendly. This paper presents an intelligent system to support EMTP simulation. The intelligent support system is composed of three stages. First, the support system selects a base case from a case database, to be modified to meet the user's requirement. Second, the expert system checks the syntax and validity of the new case data. Finally, the EMTP solution is checked to see whether the chosen models are appropriate for the frequencies contained in the solution, for the degree of imbalance, and for other criteria. If they are not appropriate, better models will be recommended to the user.

Diverse Tumorigenic Pathways in Ovarian Serous Carcinoma

This study was undertaken to analyze genetic alterations in 108 sporadic serous ovarian neoplasms to elucidate ovarian serous carcinogenesis. Our results demonstrate that K-ras mutations occur in approximately 50% of serous borderline tumors (SBTs), non-invasive micropapillary serous carcinomas (MPSCs), and invasive micropapillary serous carcinomas, which represent a morphological continuum of tumor progression. Moreover, progressive increase in the degree of allelic imbalance of chromosomes 1p, 5q, 8p, 18q, 22q, and Xp was observed comparing serous borderline tumors to noninvasive and invasive micropapillary serous carcinomas. In contrast, high-grade (conventional serous carcinoma) tumors contained wild-type K-ras in all 23 cases studied and a high frequency of allelic imbalance even in small (early) primary tumors similar to that found in advanced stage tumors. Based on these findings, we propose a dualistic model for ovarian serous carcinogenesis. One pathway involves a stepwise progression from SBT to noninvasive and then invasive MPSC. The other pathway is characterized by rapid progression from the ovarian surface epithelium or inclusion cysts to a conventional (high-grade) serous carcinoma.

The application of neural networks to vibrational diagnostics for multiple fault conditions

Vibration analysis has long been used for the detection and identification of machine fault conditions. The specific characteristics of the vibration spectrum that are associated with common fault conditions are quite well known, e.g. the BPOR spectral component reflecting bearing defects and the peak at the rotational frequency in the vibration spectrum indicating the degree of imbalance. The typical use of these features would be to determine when a machine should be taken out of operation in the presence of deteriorating fault conditions. Reliable diagnostics of deteriorating conditions may however be more problematic in the presence of simultaneous fault conditions. This paper demonstrates that the presence of a bearing defect makes it impossible to determine the degree of imbalance based on a single vibration feature, e.g. the peak at rotational frequency. In such a case, it is necessary to employ diagnostic techniques that are suited to the parallel processing of multiple features. Neural networks are the best known technique to approach such a problem. The paper demonstrates that a neural classifier using the X and Y components of both the peak at rotational frequency and the peak at BPOR frequency as input features can reliably diagnose the presence of bearing defect and can at the same time indicate the degree of imbalance. Several different neural techniques are evaluated for this purpose. It is first shown how Kohonen feature maps can be applied to do an exploratory analysis on the data, and to implement reliable classification of different bearing conditions. Different supervised neural classification techniques are then evaluated for their ability to reliably model the degree of imbalance, while also identifying the presence of defects.

COMPARISON OF CONFIDENCE INTERVALS ON THE AMONG-GROUP VARIANCE COMPONENT FOR THE UNBALANCED ONE-WAY RANDOM MODEL

ABSTRACT The purpose of this paper is to compare four methods for constructing approximate confidence intervals on the among-group variance component for the unbalanced random one-way model. Monte-Carlo simulation is used to compare the estimated coverage probabilities of these intervals. The comparison is based on a method for generating designs having specified degrees of imbalance. Two of these methods, namely, the one by Thomas and Hultquist [5] and the modified harmonic mean method, appear to be the best in most cases considered.