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Imbalance
Kinds of Imbalance Selected AbstractsDecreasing Numbers at Increasing Levels: An Investigation of the Gender Imbalance at NHHGENDER, WORK & ORGANISATION, Issue 2 2003Joyce Falkenberg Gender imbalance is a highly discussed topic in Norway, where equity is the norm. At the Norwegian School of Economics and Business Administration (NHH) the issue of gender imbalance has been on the strategic agenda of the school for the past 12 years. Because these strategies have not resulted in the reduction of the gender imbalance that was expected, it is necessary to look for further explanations. Gender imbalance can result from hiring practices, turnover, or promoting policies. In this article the focus is on retaining women in the organization, and we draw on the literature from organizational attachment to uncover additional understanding of gender imbalance. The article reports the findings from an exploratory study of organizational attachment among the faculty at NHH. Findings indicate differences between male and female faculty members and PhD students on organizational commitment, on the value and expectation of job characteristics, on the suitability of the paradigm, and on alternative job possibilities. [source] Altered distribution of natural killer cell subsets identified by CD56, CD27 and CD70 in primary and chronic human immunodeficiency virus-1 infectionIMMUNOLOGY, Issue 2 2008Kehmia Titanji Summary Human natural killer (NK) (CD3, CD56+) cells can be divided into two functionally distinct subsets, CD3, CD56dim and CD3, CD56bright. We analysed the distribution of NK cell subsets in primary and chronic human immunodeficiency virus-1 (HIV-1) infection, to determine if HIV infection stage may influence the subset distribution. In primary infection, contrary to chronic infection, the CD3, CD56dim subset was expanded compared to healthy controls. We also studied the effect of antiretroviral therapy administered early in infection and found that NK cell subset distribution was partially restored after 6 months of antiretroviral therapy in primary infection, but not normalized. Recently, NK cells have been divided into CD27, and CD27+ subsets with different migratory and functional capacity and CD27-mediated NK cell activation has been described in mice. We therefore investigated whether CD27 and/or CD70 (CD27 ligand) expression on NK cells, and thus the distribution of these novel NK subsets, was altered in HIV-1-infected patients. We found up-regulated expression of both CD27 and CD70 on NK cells of patients, resulting in higher proportions of CD27high and CD70high NK cells, and this phenomenon was more pronounced in chronic infection. Experiments conducted in vitro suggest that the high interleukin-7 levels found during HIV-1 infection may participate in up-regulation of CD70 on NK cell subsets. Imbalance of NK cell subsets and up-regulated expression of CD27 and CD70 initiated early in HIV-1 infection may indicate NK cell activation and intrinsic defects initiated by HIV-1 to disarm the innate immune response to the virus. [source] Dopamine increases renal oxygenation: a clinical study in post-cardiac surgery patientsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010BENGT REDFORS Background: Imbalance of the renal medullary oxygen supply/demand relationship can cause ischaemic acute renal failure (ARF). The use of dopamine for prevention/treatment of ischaemic ARF has been questioned. It has been suggested that dopamine may increase renal oxygen consumption (RVO2) due to increased solute delivery to tubular cells, which may jeopardise renal oxygenation. Information on the effects of dopamine on renal perfusion, filtration and oxygenation in man is, however, lacking. We evaluated the effects of dopamine on renal blood flow (RBF), glomerular filtration rate (GFR), RVO2 and renal O2 demand/supply relationship, i.e. renal oxygen extraction (RO2Ex). Methods: Twelve uncomplicated, mechanically ventilated and sedated post-cardiac surgery patients with pre-operatively normal renal function were studied. Dopamine was sequentially infused at 2 and 4 ug/kg/min. Systemic haemodynamics were evaluated by a pulmonary artery catheter. Absolute RBF was measured using two independent techniques: by the renal vein thermodilution technique and by infusion clearance of paraaminohippuric acid (PAH), with a correction for renal extraction of PAH. The filtration fraction (FF) was measured by the renal extraction of 51Cr-EDTA. Results: Neither GFR, tubular sodium reabsorption nor RVO2 was affected by dopamine, which increased RBF (45,55%) with both methods, decreased renal vascular resistance (30,35%), FF (21,26%) and RO2Ex (28,34%). The RBF/CI ratio increased with dopamine. Dopamine decreased renal PAH extraction, suggestive of a flow distribution to the medulla. Conclusions: In post-cardiac surgery patients, dopamine increases the renal oxygenation by a pronounced renal pre-and post-glomerular vasodilation with no increases in GFR, tubular sodium reabsorption or renal oxygen consumption. [source] Role of meal carbohydrate content for the imbalance of plasma amino acids in patients with liver cirrhosisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2007Ewert Schulte-Frohlinde Abstract Background and Aim:, Imbalance of circulating branched chain amino acids (BCAA) versus aromatic amino acids (AAA) and hyperinsulinemia are common metabolic alterations in patients with liver cirrhosis. The aim of this study was to characterize the effect of the carbohydrate component of a protein-rich mixed meal on postprandial plasma concentrations of 21 amino acids, insulin and C-peptide in patients with compensated liver cirrhosis. Furthermore, the effect of a dietary intervention on the metabolic alterations in cirrhotic patients was examined. Methods:, Eighteen patients with cirrhosis and 12 healthy volunteers received a protein-rich meal (pork filet 200 g) with or without carbohydrates (bread 50 g, glucose 20 g). A subgroup of four cirrhotic patients received an isoenergetic (117 kJ/kg bw) carbohydrate-enriched (60%) and -restricted (20%) diet for 7 days each. Results:, In the cirrhotic patients, basal plasma insulin and C-peptide concentrations were significantly elevated. The ingestion of a protein-rich meal without additional carbohydrates led to a significantly greater increase of insulin and C-peptide in the cirrhotic patients compared to controls. Postprandial increases of leucine and isoleucine were reduced, whereas those of phenylalanine were higher in cirrhotic patients. The addition of carbohydrates led to higher insulin and C-peptide plasma concentrations in cirrhotic patients. Postprandial BCAA increases were more impaired in the cirrhotic group after additional carbohydrate ingestion (46%vs 82%). After the carbohydrate-restricted diet for 7 days BCAA plasma levels increased but the BCAA/AAA ratio remained unaltered. Conclusions:, The carbohydrate content of a meal enhances reduction of BCAA plasma concentrations in clinically stable cirrhotic patients. An imbalanced BCAA/AAA ratio cannot be avoided by a carbohydrate-reduced diet alone, supporting mandatory BCAA supplementation. [source] Imbalance of plasma membrane ion leak and pump relationship as a new aetiological basis of certain disease statesJOURNAL OF INTERNAL MEDICINE, Issue 6 2003G. Ronquist Abstract. The basis for life is the ability of the cell to maintain ion gradients across biological membranes. Such gradients are created by specific membrane-bound ion pumps [adenosine triphosphatases (ATPases)]. According to physicochemical rules passive forces equilibrate (dissipate) ion gradients. The cholesterol/phospholipid ratio of the membrane and the degree of saturation of phospholipid fatty acids are important factors for membrane molecular order and herewith a determinant of the degree of non-specific membrane leakiness. Other operative principles, i.e. specific ion channels can be opened and closed according to mechanisms that are specific to the cell. Certain compounds called ionophores can be integrated in the plasma membrane and permit specific inorganic ions to pass. Irrespective of which mechanism ions leak across the plasma membrane the homeostasis may be kept by increasing ion pumping (ATPase activity) in an attempt to restore the physiological ion gradient. The energy source for this work seems to be glycolytically derived ATP formation. Thus an increase in ion pumping is reflected by increased ATP hydrolysis and rate of glycolysis. This can be measured as an accumulation of breakdown products of ATP and end-products of anaerobic glycolysis (lactate). In certain disease entities, the balance between ATP formation and ion pumping may be disordered resulting in a decrease in inter alia (i.a.) cellular energy charge, and an increase in lactate formation and catabolites of adenylates. Cardiac syndrome X is proposed to be due to an excessive leakage of potassium ions, leading to electrocardiographic (ECG) changes, abnormal Tl-scintigraphy of the heart and anginal pain (induced by adenosine). Cocksackie B3 infections, a common agent in myocarditis might also induce an ionophore-like effect. Moreover, Alzheimer's disease is characterized by the formation of extracellular amyloid deposits in the brain of patients. Perturbation of cellular membranes by the amyloid peptide during the development of Alzheimer's disease is one of several mechanisms proposed to account for the toxicity of this peptide on neuronal membranes. We have studied the effects of the peptide and fragments thereof on 45Ca2+ -uptake in human erythrocytes and the energetic consequences. Treatment of erythrocytes with the ,1,40 peptide, results in qualitatively similar nucleotide pattern and decrease of energy charge as the treatment with Ca2+ -ionophore A23187. Finally, in recent studies we have revealed and published in this journal that a rare condition, Tarui's disease or glycogenosis type VII, primarily associated with a defect M-subunit of phosphofructokinase, demonstrates as a cophenomenon an increased leak of Ca2+ into erythrocytes. [source] Inflammatory Cytokine Imbalance after Coronary Angioplasty: Links with Coronary AtherosclerosisJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 4 2007NATALE DANIELE BRUNETTI M.D., Ph.D. Aim:To investigate release of some inflammatory cytokines (Cys) after coronary angioplasty and its links with coronary atherosclerosis. Methods:Twenty-seven consecutive subjects with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) were enrolled in the study: serial blood samples were taken in order to evaluate plasma concentrations of Interleukin (IL)-2, IL-10, IL-18, TNF,, and IFN, just before PCI at 12 and 24 hours. Patients were then divided, considering balance between each inflammatory Cy and IL-10, an antiinflammatory Cy, into four groups, ranging from a prevalent antiinflammatory response (stable inflammatory Cy,increasing IL-10 values) to a marked inflammatory imbalance (increasing inflammatory Cy,stable IL-10 values). Results:All Cys showed significant increases in plasma concentrations if compared with baseline values. Release curves were not significantly different when comparing subjects with ST-elevation myocardial infarction (STEMI) versus unstable angina,non-STEMI (UA-NSTEMI), diabetics versus controls. Subjects with marked inflammatory response showed a higher incidence of stenosis on left anterior descending (LAD) coronary artery (IL-2 ,2 and IFN, P < 0.05); Cy release was higher in patients with multivessel coronary disease (IL-2 and IFN,, ANOVA P < 0.01). Correlations were also referable between Cys and myocardial enzyme release. Subjects treated with sirolimus-eluting stents (SES) showed significantly lower Cy periprocedure ratio if compared with those treated with bare metal stents. Conclusions:A significant Cy release is detectable after PCI: inflammatory response seems to correlate with both PCI due to plaque instabilization and coronary atherosclerosis. A blunted inflammatory response is detectable in subjects treated with SES. [source] Apoptosis and proliferation in Helicobacter pylori -associated gastric intestinal metaplasiaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2001W. K. Leung Background: Imbalance between apoptosis and proliferation may be one of the mechanisms underlying H. pylori associated gastric carcinogenesis. Aim: To examine the cell kinetics of gastric intestinal metaplasia and the effect of H. pylori eradication. Methods: Endoscopic gastric biopsies were obtained from 100 H. pylori -infected patients. Apoptosis was determined by triphosphate nick-end labelling (TUNEL) and apoptotic nuclei counting, whereas proliferation was assessed by Ki67 immunostaining. Gastric biopsies were repeated in a sub-group of intestinal metaplasia patients after H. pylori eradication. Results: Antral apoptotic index was significantly lower in intestinal metaplasia than in non-intestinal metaplasia (0.19% vs. 0.51%; P < 0.0001) whereas the level of proliferation was comparable (28% vs. 22%, P=0.15). Serial antral biopsies taken from 14 intestinal metaplasia patients before and 1 year after H. pylori eradication showed a significant drop in proliferation in both intestinal metaplasia (50% vs. 12%, P < 0.001) and non-intestinal metaplasia area (47% vs. 9%, P < 0.001). A similar fall in apoptosis was detected in non-metaplastic region (0.58% vs. 0.38%, P < 0.001) but not in intestinal metaplasia (0.24% vs. 0.27%, P=0.56), resulting in a significant increase in the apoptosis/proliferation ratio (0.005,0.021; P=0.03). Conclusions: Dysregulation in apoptosis control of gastric intestinal metaplasia may contribute to gastric carcinogenesis, which may be retarded by clearance of H. pylori. [source] NMR-based metabonomics analysis of mouse urine and fecal extracts following oral treatment with the broad-spectrum antibiotic enrofloxacin (Baytril)MAGNETIC RESONANCE IN CHEMISTRY, Issue S1 2009Lindsey E. Romick-Rosendale Abstract The human gastrointestinal tract is home to hundreds of species of bacteria and the balance between beneficial and pathogenic bacteria plays a critical role in human health and disease. The human infant, however, is born with a sterile gut and the complex gastrointestinal host/bacterial ecosystem is only established after birth by rapid bacterial colonization. Composition of newborn gut flora depends on several factors including type of birth (Ceasarian or natural), manner of early feeding (breast milk or formula), and exposure to local, physical environment. Imbalance in normal, healthy gut flora contributes to several adult human diseases including inflammatory bowel (ulcerative colitis and Crohn's disease) and Clostridium difficile associated disease, and early childhood diseases such as necrotizing enterocolitis. As a first step towards characterization of the role of gut bacteria in human health and disease, we conducted an 850 MHz 1H nuclear magnetic resonance spectroscopy study to monitor changes in metabolic profiles of urine and fecal extracts of 15 mice following gut sterilization by the broad-spectrum antibiotic enrofloxacin (also known as Baytril). Ten metabolites changed in urine following enrofloxacin treatment including decreased acetate due to loss of microbial catabolism of sugars and polysaccharides, decreased trimethylamine- N -oxide due to loss of microbial catabolism of choline, and increased creatine and creatinine due to loss of microbial enzyme degradation. Eight metabolites changed in fecal extracts of mice treated with enrofloxacin including depletion of amino acids produced by microbial proteases, reduction in metabolites generated by lactate-utilizing bacteria, and increased urea caused by loss of microbial ureases. Copyright © 2009 John Wiley & Sons, Ltd. [source] Ultraviolet B Light-induced Nitric Oxide/Peroxynitrite Imbalance in Keratinocytes,Implications for Apoptosis and NecrosisPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2010Shiyong Wu Elevation of nitric oxide (NO,) can either promote or inhibit ultraviolet B light (UVB)-induced apoptosis. In this study, we determined real-time concentration of NO, and peroxynitrite (ONOO,) and their role in regulation of membrane integrity and apoptosis. Nanosensors (diameter 300,500 nm) were used for direct in situ simultaneous measurements of NO, and ONOO, generated by UVB in cultured keratinocytes and mice epidermis. An exposure of keratinocytes to UVB immediately generated ONOO, at maximal concentration of 190 nm followed by NO, release with a maximal concentration of 91 nm. The kinetics of UVB-induced NO,/ONOO, was in contrast to cNOS agonist stimulated NO,/ONOO, from keratinocytes. After stimulating cNOS by calcium ionophore (CaI), NO, release from keratinocytes was followed by ONOO, production. The [NO,] to [ONOO,] ratio generated by UVB decreased below 0.5 indicating a serious imbalance between cytoprotective NO, and cytotoxic ONOO,,a main component of nitroxidative stress. The NO,/ONOO, imbalance increased membrane damage and cell apoptosis was partially reversed in the presence of free radical scavenger. The results suggest that UVB-induced and cNOS-produced NO, is rapidly scavenged by photolytically and enzymatically generated superoxide (O2,,) to produce high levels of ONOO,, which enhances oxidative injury and apoptosis of the irradiated cells. [source] The association of socioeconomic status and psychosocial and physical workplace factors with musculoskeletal injury in hospital workers,AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 4 2007Marion Gillen RN Abstract Background The combined effect of socioeconomic, organizational, psychosocial, and physical factors on work-related musculoskeletal disorders (WRMSDs) were studied in a heterogeneous, socioeconomically diverse sample (cases and their matched referents) of hospital workers. Methods Cases were defined by a new acute or cumulative work-related musculoskeletal injury; referents were matched by job group, shift length, or at random. Information was obtained through telephone interviews and on-site ergonomics observation. Questionnaire items included sociodemographic variables, lost work time, work effectiveness, health status, pain/disability, and psychosocial working conditions using Effort Reward Imbalance (ERI) and Demand-Control (DC) models. Two multivariate models were tested: Model 1 included occupation as a predictor; Model 2 included education,income as a predictor. Results Cases reported greater pain, disability, lost time, and decreased work effectiveness than the referents. Model 1 was statistically significant for neck/upper extremity injury (Chi-square,=,19.3, P,=,0.01), back/lower extremity injury (Chi-square,=,14.0, P,=,0.05), and all injuries combined (Chi-square,=,25.4, P,=,0.001). "Other Clinical" occupations (34% mental health workers) had the highest risk of injury (OR 4.5: 95%CI, 1.7,12.1) for all injuries. The ERI ratio was a significant predictor for neck and upper extremity (OR 1.5: 95%CI, 1.1,1.9) and all injuries (OR 1.3; 95%CI, 1.04,1.5), per SD change in score. Conclusions In this study, the risk of WRMSDs was more strongly influenced by specific psychosocial and physical job-related exposures than by broad socioeconomic factors such as education and income. Am. J. Ind. Med. 2007. © 2007 Wiley-Liss, Inc. [source] Prime Minister Manmohan Singh on India's Gender ImbalancePOPULATION AND DEVELOPMENT REVIEW, Issue 2 2008Article first published online: 28 JUN 200 No abstract is available for this article. [source] ORIGINAL ARTICLE: Imbalance of T-cell Transcription Factors Contributes to the Th1 Type Immunity Predominant in Pre-eclampsiaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Zhou Jianjun Problem, Extensive studies have demonstrated that Th1 type immunity is predominant in pre-eclampsia, but there is little concern with regard to the intracellular mechanisms behind this initial T-cell polarization. In this study, we investigated whether the imbalance of the T-cell transcription factors contributes to it. Method of study, A total of 15 pre-eclamptic patients and 15 healthy pregnant women were enrolled in this study. The expression levels of transcription factors for Th1 (T-bet), Th2 (GATA3), Th17 (RORc) and Treg (FOXP3) cells, together with the Th1/Th2 status, were simultaneously investigated in both peripheral blood mononuclear cells (PBMCs) and decidua. Results, The expression levels of FOXP3 mRNA were decreased in both PBMCs and decidua from pre-eclamptic patients compared with healthy pregnant women (P < 0.05), and T-bet mRNA and RORc mRNA were significantly increased (P < 0.05), while Th1/Th2 balance shifted toward the Th1 immunity. Furthermore, there was a negative correlation between FOXP3 mRNA and Th1 cells (P < 0.05), and the expression level of T-bet mRNA correlated strongly with Th1 cells (P < 0.05). Conclusion, Decreased expression of FOXP3 mRNA and increased expression of T-bet mRNA may contribute to Th1 type immunity predominant in pre-eclampsia. [source] TH1/TH2,3 Imbalance due to Cytokine-Producing NK, ,, T and NK-,, T Cells in Murine Pregnancy Decidua in Success or Failure of PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2001DAVID A. CLARK PROBLEM: Recurrent spontaneous abortion in DBA/2-mated CBA/J mice has been attributed to the production of Th1 cytokines (tumor necrosis factor [TNF]-, and interferon [IFN]-,) by asialoGM1+ natural killer (NK) cells and V,1.1,6.3+ T cells that infiltrate decidua by day 6.5, during the peri-implantation period. Abortions can be prevented by a second population of V,1.1,6.3 cells, which infiltrate on day 8.5 of gestation, and produce the Th2 cytokine interleukin (IL)-10 and Th3 cytokine transforming growth factor (TGF)-,2. In low abortion rate immunocompetent mice, most of the TGF-,2 is derived from ,, T cells. However, TGF-,2-producing cells are present in the decidua of pregnant severe combined immune deficient (SCID) mice, which lack ,, T cells. METHODS: The cells in day 13.5 decidua of CBA×DBA/2 matings and SCID×SCID matings were identified using flow cytometry and combined surface staining for ,, and/or asialoGM1, and intracellular cytokine staining for TNF-,, IFN-,, and TGF-,2,3. RESULTS: TGF-,2 and TNF-, were found in asialoGM1+ NK cells in SCID mouse decidua. In CBA×DBA/2 mated mice, two major and one minor subsets of cytokine-positive cells were identified: -,,-only T cells, double positive asialoGM1+,,+ (NK-,, T) cells, and a small number of asialoGM1+,,, NK-only cells. The NK-only and NK-,, T subsets showed a greater Th1/Th2,3 pattern of intracellular staining compared with the ,,-only subset. In the CBA×DBA/2 and SCID×SCID systems, Th1/Th2,3 ratios could not predict actual observed abortion rates but did correlate with susceptibility to abortions (if exposed to an additional stimulus such as stress). The known effect of in vivo administration of anti-asialoGM1 antibody on abortion rates within groups of mice exposed to such stresses could also be predicted. CONCLUSION: ,,+ cells in decidua (e.g. V,1+ cells which can recognize trophoblasts) differ based on the presence or absence of the NK marker-asialo-GM1. NK-,, T cells may be quite important in the Th1 response in early pregnancy that predisposes to abortions in CBA×DBA/2 matings, whereas ,, T-only cells appear to be protective. In pregnant SCID mice, the TNF-,+/TGF-,2+ NK population is greatly expanded. An activating stimulus (such as stress or endotoxin) appears to be as important in triggering abortions, as is the Th1/Th2,3 ratio at the feto,maternal interface. [source] ECG Manifestations of Multiple Electrolyte Imbalance: Peaked T Wave to P Wave ("Tee-Pee Sign")ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2009Amer M. Johri M.D. The surface electrocardiogram (ECG) is a useful instrument in the detection of metabolic disturbances. The accurate characterization of these disturbances, however, may be considerably more difficult when more than one metabolic abnormality is present in the same individual. While "classic" ECG presentations of common electrolyte disturbances are well described, multiple electrolyte disturbances occurring simultaneously may generate ECG abnormalities that are not as readily recognizable. We report a case of hyperkalemia, with concurrent hypocalcemia and hypomagnesemia resulting in (1) peaking of the T wave, (2) a prominent U wave, and (3) prolongation of the descending limb of the T wave such that it overlapped with the next P wave. In this particular ECG from a patient with combined electrolyte imbalance, we have dubbed the unusual appearance of the segment between the peak of the T wave to the next P wave as the "tee-pee" sign. [source] Microsatellite Instability And Allelic Imbalance In Primary And Secondary Colorectal CancerANZ JOURNAL OF SURGERY, Issue 8 2000Anne Schneider Background: Several studies of colorectal cancer have shown an association between the number and type of genomic defects and the stage of disease. A subset of colorectal tumours are due to inactivation of DNA mismatch repair genes and these tumours exhibit microsatellite instability. The aim of the present study was to compare and contrast the genomic defects present in both the primary and metastatic stages of the disease using microsatellite probes. Methods: Modifications of the allelic profiles of 25 microsatellite regions were studied in a total of 85 colorectal tumours using fluorescent polymerase chain reaction (PCR) technology and subsequent direct analysis on an automatic sequencer. This approach was used because it allows the study of microsatellite instability and allelic imbalance. Stepwise logistic regression analysis was used to develop a model to predict whether the tumour was primary or secondary from the percentage of allelic imbalance. Subsequently, a group of 17 patients with primary colorectal tumours was analysed prospectively to test the proposed model. Results: Six of 39 primary tumours showed microsatellite instability compared to 0 of 29 liver metastases (P = 0.03). Primary tumours showed significantly less allelic imbalance than liver metastases (P < 0.001). Three probes (d18s53, d9s158 and d10s191) were selected for use in a model to classify a tumour as primary or secondary on the basis of the degree of allelic imbalance. When tested prospectively this model had a specificity of 82%. Conclusions: The present study demonstrates the potential importance of using microsatellite probes both as a diagnostic tool and as a research technique to investigate the mechanisms of tumour progression. An important clinical finding is that none of the colorectal liver metastases showed microsatellite instability (0 of 29). This analysis also confirmed other work that has shown a direct relationship between the degree of allelic imbalance and the stage of disease. [source] Imbalance between interleukin-1 agonists and antagonists: relationship to severity of inflammatory bowel diseaseCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2004O. LUDWICZEK SUMMARY Interleukin (IL)-1 is a key mediator in the pathogenesis of inflammatory bowel disease (IBD). Naturally occurring IL-1 modulators include IL-1 receptor antagonist (IL-1Ra), IL-1 soluble receptor Type I (IL-1sRI), IL-1sRII and IL-1 receptor accessory protein (AcP). Systemic and mucosal levels of IL-1 soluble receptors remain unknown in IBD. Plasma or colonic tissues were obtained from 185 consecutive unselected patients with Crohn's disease (CD) or ulcerative colitis (UC) and from 52 control subjects. Plasma and colonic explant culture supernatants were assessed for IL-1,, IL-1,, IL-1Ra, IL-1sRI and IL-1sRII. Plasma IL-1Ra levels were higher in UC (+93%) than in healthy subjects. IL-1, and IL-1, were not detected. IL-1sRII levels were marginally lower in CD (,10%) and UC (,9%), whereas IL-1sRI levels were elevated in CD (+28%) only. Plasma IL-1sRI levels correlated positively (P < 0·01) with Crohn's disease activity index (r = 0·53), C-reactive protein (r = 0·46) and ,1-acid glycoprotein (r = 0·42). In colonic explant cultures, IL-1, and IL-1Ra levels were elevated in non-lesional (+233% and +185% respectively) and lesional CD (+353% and +1069%), lesional UC (+604% and +1138%), but not in non-lesional UC. IL-1, was elevated in lesional UC (+152%) and CD (+128%). In contrast, IL-1sRII levels were elevated in non-lesional CD (+65%), but remained unchanged in lesional CD, non-lesional and lesional UC. IL-1sRI levels did not differ between patient and control groups. These results indicate that (i) the proinflammatory moiety IL-1sRI is a systemic marker of inflammation and activity in CD and (ii) local shedding of the functional antagonist IL-1sRII may dampen colonic inflammation in CD, but not in UC. [source] Parallel space-filling curve generation through sortingCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 10 2007J. Luitjens Abstract In this paper we consider the scalability of parallel space-filling curve generation as implemented through parallel sorting algorithms. Multiple sorting algorithms are studied and results show that space-filling curves can be generated quickly in parallel on thousands of processors. In addition, performance models are presented that are consistent with measured performance and offer insight into performance on still larger numbers of processors. At large numbers of processors, the scalability of adaptive mesh refined codes depends on the individual components of the adaptive solver. One such component is the dynamic load balancer. In adaptive mesh refined codes, the mesh is constantly changing resulting in load imbalance among the processors requiring a load-balancing phase. The load balancing may occur often, requiring the load balancer to perform quickly. One common method for dynamic load balancing is to use space-filling curves. Space-filling curves, in particular the Hilbert curve, generate good partitions quickly in serial. However, at tens and hundreds of thousands of processors serial generation of space-filling curves will hinder scalability. In order to avoid this issue we have developed a method that generates space-filling curves quickly in parallel by reducing the generation to integer sorting. Copyright © 2007 John Wiley & Sons, Ltd. [source] Data partitioning-based parallel irregular reductionsCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 2-3 2004Eladio Gutiérrez Abstract Different parallelization methods for irregular reductions on shared memory multiprocessors have been proposed in the literature in recent years. We have classified all these methods and analyzed them in terms of a set of properties: data locality, memory overhead, exploited parallelism, and workload balancing. In this paper we propose several techniques to increase the amount of exploited parallelism and to introduce load balancing into an important class of these methods. Regarding parallelism, the proposed solution is based on the partial expansion of the reduction array. Load balancing is discussed in terms of two techniques. The first technique is a generic one, as it deals with any kind of load imbalance present in the problem domain. The second technique handles a special case of load imbalance which occurs whenever a large number of write operations are concentrated on small regions of the reduction arrays. Efficient implementations of the proposed optimizing solutions for a particular method are presented, experimentally tested on static and dynamic kernel codes, and compared with other parallel reduction methods. Copyright © 2004 John Wiley & Sons, Ltd. [source] (Re)designing mediation to address the nuances of power imbalanceCONFLICT RESOLUTION QUARTERLY, Issue 2 2001Ilan G. Gewurz This paper addresses the complex relationship between negotiating power and mediation. It begins with the premise that to say in absolute terms that mediation is or is not an effective way of dealing with power imbalance is to ignore the complexity of both the concept of power and the range of processes that can be deemed mediation. This article examines sources of power in an effort to develop a clear, yet thorough, understanding of negotiating power. It then turns to the scholarship on mediation, highlighting key characteristics that distinguish mediation approaches from one another and advancing the debate on what constitutes mediation. Finally, the article highlights bow a specific style of mediation may be appropriate for a given situation, depending on the existing power dynamics between the disputing parties. [source] CONSENT, COMMODIFICATION AND BENEFIT-SHARING IN GENETIC RESEARCH1DEVELOPING WORLD BIOETHICS, Issue 2 2004DONNA DICKENSON ABSTRACT The global value of the biotechnology industry is now estimated at 17 billion dollars, with over 1300 firms involved as of the year 2000.2 It has been said that ,What we are witnessing is nothing less than a new kind of gold rush, and the territory is the body.' As in previous gold rushes, prospectors are flooding into unexplored and ,wide open' territories from all over the world, with possible ramifications for exploitation of Third World populations. These territories are also the Wild West of bioethics insofar as the law has very little hold on them: existing medical and patent law, such as the Moore and Chakrabarty cases, exert little control over powerful economic interests in both the United States and Europe. In the absence of a unified and consistent law on property in the body, the focus is increasingly on refining the consent approach to rights in human tissue and the human genome, with sensitive and promising developments from the Human Genetics Commission and the Department for International Development consultation on intellectual property. These developments incorporate the views of vulnerable genetic communities such as Native Americans or some Third World populations, and should be welcomed because they recognise the power imbalance between such groups and First World researchers or firms. However, they also highlight the continued tension about what is really wrong with commodifying human tissue or the human genome. Where's the injustice, and can it be solved by a more sophisticated consent procedure? [source] A Bigger Piece of a Very Small Pie: Intrahousehold Resource Allocation and Poverty Reduction in AfricaDEVELOPMENT AND CHANGE, Issue 1 2007Bridget O'Laughlin ABSTRACT Feminist research has convincingly shown that an increase in household income does not necessarily lead to improvement in the well-being of all members of the household. More questionable is the policy conclusion often drawn from this research for rural Africa: redressing gender imbalance in control of productive resources will significantly reduce poverty. This contribution argues that the evidence and analysis presented by two studies repeatedly cited to show that gender inequality is inefficient are problematic. It is mythical to suggest that tinkering with women's market position by exchanging unequal collective rights to productive resources for individual ones will decisively reduce rural poverty in Africa. That will depend on the restructuring of long-term and deeply unequal processes of integration in the market, not on a firmer insertion of women within existing patterns of individualization and commodification of productive resources. [source] Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in menDIABETIC MEDICINE, Issue 12 2007V. Rochira Abstract Aims The role of sex steroids in glucose and insulin metabolism in men remains unclear. To investigate the effects of sex steroids and oestrogen on insulin sensitivity in men, we studied two male adults with aromatase deficiency (subject 1 and subject 2). Methods The effects of transdermal oestradiol (tE2) treatment at different dosages on insulin sensitivity were studied before tE2 treatment (phase 1), and after 6 months (phase 2) and 12 months of tE2 treatment (phase 3) by means of homeostasis model assessment,insulin resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI), insulin tolerance test (ITT), and oral glucose tolerance test (OGTT). The latter was performed only in subject 1, as subject 2 suffered from Type 2 diabetes. Results The restoration of normal serum oestradiol led to improved insulin sensitivity, as shown by changes in HOMA-IR and QUICKI. The ITT provided evidence of improved insulin sensitivity during tE2 treatment. Insulin secretion after OGTT was reduced during tE2 treatment in subject 1. After 12 months of tE2 treatment, insulin sensitivity was improved compared with in phases 1 and 2. Conclusions The study suggests a direct involvement of oestrogens in insulin sensitivity, and supports a possible role of oestradiol : testosterone ratio, which may be as influencial as the separate actions of each sex steroid on glucose homeostasis. [source] A longitudinal observational study of insulin therapy and glycaemic control in Scottish children with Type 1 diabetes: DIABAUD 3DIABETIC MEDICINE, Issue 11 2006Scottish Study Group for the Care of the Young with Diabetes Abstract Objective/background, Our objective was to investigate glycaemic control in children with Type 1 diabetes in Scotland and to analyse the effect of changing ,conventional' insulin regimen strategies on outcome. DIABAUD 2 (1997,1998) (D2) demonstrated that average glycaemic control in young people with Type 1 diabetes in Scotland was poor, with mean HbA1c of 9.0%. Over 90% were then treated with a twice-daily insulin regimen. The aim of DIABAUD 3 (2002,2004) (D3) was to determine if control had improved, and to examine changes in insulin regimen and effects on glycaemic control. Methods, In DIABAUD 3, data were collected prospectively on children aged < 15 years. in nine out of 15 centres throughout Scotland. HbA1c on 986 subjects was measured in a single Diabetes Control and Complications Trial-aligned laboratory. The results were compared with those from DIABAUD 2, for the same nine centres. Multiple regression comparison was performed to adjust for imbalance in relevant confounders (e.g. age, duration, height and weight, insulin dose and centre). Results, For D3, the age range was 1.1,14.9 years (62% aged 10,14 years), mean (± sd) HbA1c 9.2% ± 1.5 (compared with D2, 9.0% ± 1.5). Only 9.7% achieved the target of HbA1c < 7.5%. The number of subjects in D3 on twice-daily injections was 51% (compared with 94% in D2), 43% on three-times-daily injections (2% in D2) and 2.3% on four or more (1.9% in D2): HbA1c did not differ in these groups. In both the D2 and D3 cohorts, HbA1c rose with age. After adjustment for other variables in the combined datasets, insulin regimen was not a significant predictor of HbA1c (F = 0.19, d.f. = 3, 1774; P = 0.90). Conclusion, The glycaemic control in young people in Scotland remains poor and above the national target. Over 4 years, moderate intensification of insulin therapy (i.e. from two to three injections each day, usually reflecting splitting of the evening dose) across the population failed to improve the average HbA1c and reduce the increase seen with age. A national programme away from ,conventional' to an ,intensive' regimen of insulin therapy is required. [source] Quantitative FISH analysis on interphase nuclei may improve diagnosis of DNA diploid breast cancersDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2002Khuong Truong Abstract The detection of DNA aneuploid cells using flow cytometry is an indication for the presence of tumor cells, but when DNA diploid cells are found in 25,33% of the cases, the diagnostic and prognostic significance of DNA ploidy is more limited. We analyzed interphase nuclei after in situ hybridization and using image cytometry on 50 breast tumors with diploid DNA content to investigate whether early chromosome rearrangements were detectable and if their occurrence was clinically significant. Imbalances between the two arms of chromosome 1 were found in 55% of the cases and values ranged from 1.5,3.0. Comparison with histological data showed that Grade I tumors mainly have imbalances (67%) and that Grade III tumors were mainly without the imbalance (67%), whereas Grade II tumors were intermediate (50% imbalance). These data suggest that the diagnosis of DNA diploid cases may be improved by using interphase FISH. In addition, the data also indicates that early breast tumors may have different genetic origins, which is important in the comprehension of tumor malignancy in early stages, especially for preinvasive lesions. Diagn. Cytopathol. 2002;26:213,216. © 2002 Wiley-Liss, Inc. [source] Cognitive impairment in schizophrenia:its impact on social functioningACTA PSYCHIATRICA SCANDINAVICA, Issue 400 2000P. F. Liddle Objective: To examine cognitive impairment in schizophrenia and its impact on social functioning. Method: Cohort studies recording cognitive and social development, studies of predictors of poor community outcome, and evidence from brain imaging studies are reviewed. Results: Executive function deficits, and poor performance in verbal memory, vigilance, and working memory tests are strong predictors of poor community outcome and impairment in skills learning. PET scans of regional cerebral blood flow suggest a dynamic imbalance between different cerebral areas rather than overall loss of brain function. Conclusion: Chronic cognitive impairment is the strongest predictor of social disability. Results suggest that the impairment of brain function associated with executive deficits is not necessarily irreversible and may therefore be treatable with appropriate drug therapy. [source] Mechanistic studies of blood pressure in rats treated with a series of cholesteryl ester transfer protein inhibitors,DRUG DEVELOPMENT RESEARCH, Issue 1 2009Michael DePasquale Abstract ILLUMINATE, the Phase 3 clinical trial of morbidity and mortality (M&M) with the cholesteryl ester transfer protein inhibitor (CETPi), torcetrapib (CP-529,414), was terminated in December 2006 due to an imbalance in all cause mortality. The underlying cause of the M&M remains undetermined. While torcetrapib produced dose-related increases in blood pressure in clinical trials, the mechanism of the increase in blood pressure is also undetermined. The pressor effects of torcetrapib and structurally related compounds were studied in several pathways involved in blood pressure control. Studies were conducted in rats treated with a series of structurally related molecules (CP-529,414, CP-532,623, PF-868,348, CP-746,281, CP-792,485, PF-868,343, and CE-308,958). CP-529,414, CP-532,623, CP-868,343, and CP-792,485 are potent CETP inhibitors; PF-868,348 is weakly potent and CP-746,281 and CE-308,958 are CETP-inactive. Changes in blood pressure were determined in conscious animals in conjunction with pharmacologic blockade of numerous pressor agents/pathways. Torcetrapib and CP-532,623 increased blood pressure following both chronic PO and acute IV administration. The CETP-inactive enantiomer of CP-532,623, CP-746,281 failed to raise blood pressure. PF-868,348, a structural analogue with ,50-fold lower CETPi activity also displayed pressor activity. Blockade of adrenergic, cholinergic, angiotensin, endothelin, NOS, Rho kinase, and thromboxane pathways failed to attenuate the pressor response. These data demonstrate that the blood pressure activity seen with torcetrapib can be dissociated from CETP inhibitor pharmacology and numerous pharmacology pathways can be discounted in the attempt to understand the molecular basis of the pressor pharmacology. Drug Dev Res 70:2009 © 2009 Wiley-Liss, Inc. [source] Follow-up of an exercise-based treatment for children with reading difficultiesDYSLEXIA, Issue 2 2007David Reynolds Abstract This study reports the results of a long-term follow-up of an exercise-based approach to dyslexia-related disorders (Reynolds, Nicolson, & Hambly, Dyslexia, 2003; 9(1): 48,71). In the initial study, children at risk of dyslexia were identified in 3 years of a junior school. One half then undertook a 6 month, home-based exercise programme. Evaluation after 6 months indicated that the exercise group improved significantly more than the controls on a range of cognitive and motor skills. Critics had suggested that the improvement might be attributable to artifactual issues including Hawthorne effects; an initial literacy imbalance between the groups; and inclusion of non-dyslexic participants. The present study evaluated the issue of whether the gains were maintained over the following 18 months, and whether they were in some sense artifactual as postulated by critics of the original study. Comparison of (age-adjusted) initial and follow-up performance indicated significant gains in motor skill, speech/language fluency, phonology, and working memory. Both dyslexic and non-dyslexic low achieving children benefited. There was also a highly significant reduction in the incidence of symptoms of inattention. Interestingly there were no significant changes in speeded tests of reading and spelling, but there was a significant improvement in (age-adjusted) reading (NFER). It is concluded that the gains were indeed long-lasting, and that the alternative hypotheses based on potential artifacts were untenable, and that the exercise treatment therefore achieved its applied purpose. Further research is needed to determine the underlying reasons for the benefits. Possible (and potentially synergistic) explanations include: improved cerebellar function (neural level); improved learning ability and/or attentional ability (cognitive level); improved self-esteem and self-efficacy (affective level); and improved parental/familial support (social level). Copyright © 2006 John Wiley & Sons, Ltd. [source] Gamete production and sexual size dimorphism in an insect (Orchesella cincta) with indeterminate growthECOLOGICAL ENTOMOLOGY, Issue 2 2002G. Ernsting Abstract 1. The relationship of growth and body size with reproductive effort in animal species has been studied much less for males than for females. This imbalance applies to Orchesella cincta (L.) (Collembola), an insect with indeterminate growth, in which egg production is related positively to body size and negatively to growth. 2. To allow a comparison of the reproductive effort of male and female O. cincta, development and growth in immature stages of both sexes, and growth and spermatophore production for adult males were studied. 3. Embryonic development time and hatchling size did not differ between prospective males and females, but from hatching on the trajectories diverged, with males growing more slowly and maturing earlier and at a much smaller body size than females. 4. Neither the number of spermatophores deposited in the first adult instar (= inter-moult period) nor the total number of spermatophores deposited during seven instars was related to body size or growth. 5. Differences in growth rate between instars with and without spermatophore deposition indicated that the physiology of spermatophore production inhibits growth, which, however, was compensated for during the next instar. 6. The difference in the relationship of gamete production with body size and growth between males and females explains the divergence of their size at maturity. [source] Separating the influence of resource ,availability' from resource ,imbalance' on productivity,diversity relationshipsECOLOGY LETTERS, Issue 6 2009Bradley J. Cardinale Abstract One of the oldest and richest questions in biology is that of how species diversity is related to the availability of resources that limit the productivity of ecosystems. Researchers from a variety of disciplines have pursued this question from at least three different theoretical perspectives. Species energy theory has argued that the summed quantities of all resources influence species richness by controlling population sizes and the probability of stochastic extinction. Resource ratio theory has argued that the imbalance in the supply of two or more resources, relative to the stoichiometric needs of the competitors, can dictate the strength of competition and, in turn, the diversity of coexisting species. In contrast to these, the field of Biodiversity and Ecosystem Functioning has argued that species diversity acts as an independent variable that controls how efficiently limited resources are utilized and converted into new tissue. Here we propose that all three of these fields give necessary, but not sufficient, conditions to explain productivity,diversity relationships (PDR) in nature. However, when taken collectively, these three paradigms suggest that PDR can be explained by interactions among four distinct, non-interchangeable variables: (i) the overall quantity of limiting resources, (ii) the stoichiometric ratios of different limiting resources, (iii) the summed biomass produced by a group of potential competitors and (iv) the richness of co-occurring species in a local competitive community. We detail a new multivariate hypothesis that outlines one way in which these four variables are directly and indirectly related to one another. We show how the predictions of this model can be fit to patterns of covariation relating the richness and biomass of lake phytoplankton to three biologically essential resources (N, P and light) in a large number of Norwegian lakes. [source] China and the world financial markets 1870,1939: Modern lessons from historical globalization1ECONOMIC HISTORY REVIEW, Issue 2 2007WILLIAM N. GOETZMANN In this article we review the development of Chinese capital markets over a crucial period in the history of markets worldwide, and place that development in context. Despite fundamental differences between China today and China 100 years ago, it is still important to consider the effects of an imbalance between domestic and international investor markets, and the mismatch between domestic and foreign expectations about investor protection. The lessons of the last century suggest that China today should consider opening Chinese investor access to foreign capital markets in order to equilibrate the level of diversification between foreign and domestic investors. In addition, our analysis suggests that protecting of domestic corporate investor rights is at least as important as protecting foreign investor rights. [source] |