bluuebunny/crossref_metadata_2025 huggingface dataset:
Scanning lidar: a means of characterizing the Noranda-Hornesmelter plume
Authors: Strawbridge K.B.
Published: June 2006

The Meteorological Service of Canada has recently developed a mobile scanning lidar facility (RASCAL: Rapid Acquisition SCanning Aerosol Lidar) capable of fast azimuth and elevation scanning profiles of the lower troposphere. Lidar is a remote sensing technique that provides high temporal and spatial information on atmospheric particulates and was ideally suited for characterizing stack plume dynamics. RASCAL was located predominantly downwind of the Noranda-Horne smelter stack source located in northern Quebec. Two three-week periods during February (winter) and July/August (summer) of 2000 were chosen to examine the behaviour of the plume because of the differences in humidity and boundary layer dynamics. The scanning speeds were adjusted to allow a complete scanning profile to be collected within 30–60 seconds. Along-plume-axis and cross-sectional scans provided an opportunity to directly measure plume dynamics and interaction with the planetary boundary layer, including the ability to detect fumigation events. Several algorithms have been developed to quantify the area, shape, horizontal and vertical extents of the plume as a function of the distance from source. Examples are shown where the cross-sectional area of the plume remained constant at a given distance from source even though its shape was highly variable. Also, boundary layer height, wind speed and direction of the plume can be extracted from the RASCAL data under certain conditions. These data are valuable for comparison with model predictions as well as providing initialization input for long range dispersion models.
In Vivo Migration: A Germ Cell Perspective
Authors: Kunwar Prabhat S. , Siekhaus Daria E. , Lehmann Ruth
Published: June 2006

The basic concepts of the molecular machinery that mediates cell migration have been gleaned from cell culture systems. However, the three-dimensional environment within an organism presents migrating cells with a much greater challenge. They must move between and among other cells while interpreting multiple attractive and repulsive cues to choose their proper path. They must coordinate their cell adhesion with their surroundings and know when to start and stop moving. New insights into the control of these remaining mysteries have emerged from genetic dissection and live imaging of germ cell migration in Drosophila, zebrafish, and mouse embryos. In this review, we first describe germ cell migration in cellular and mechanistic detail in these different model systems. We then compare these systems to highlight the emerging principles. Finally, we contrast the migration of germ cells with that of immune and cancer cells to outline the conserved and different mechanisms.
Anodic Oxide Growth on Tantalum with AC + DC Fields: II . Modeling and Theory
Authors: Young Lawrence , Yang Ta‐Ming , Backhouse Christopher
Published: June 2006

The small signal ac response of the ionic conductivity process, investigated in Part I , with its inductive phase relation between ionic current and field, is a manifestation of the dependence of the ionic current density on the previous history of the film. This history dependence is probably caused by structural changes in the oxide. Equations previously formulated to predict the ionic current density for all situations were modified to account for the observed behavior by introducing a distribution of relaxation times. The type of distribution found is consistent with structural changes in a glassy oxide. The relaxation times involved in the adjustment of the structure to a new field are expected to be a function of the field, temperature, and the state of the oxide. For the present experiments, since the state of the oxide corresponded to steady state (growth at constant current and field for long enough),

τ

m

could be fitted by a function of field and temperature alone. The implications of the fact that

τ

 

m

was close to inversely proportional to the ionic current density independent of temperature are discussed.
Temperature‐Dependent Methanol Electro‐Oxidation on Well‐Characterized Pt‐Ru Alloys
Authors: Gasteiger Hubert A. , Marković Nenad , Ross Philip N. , Cairns Elton J.
Published: June 2006

The kinetics of methanol electro‐oxidation on well‐characterized Pt‐Ru alloy surfaces were measured in sulfuric acid solution as a function of temperature. The alloy surfaces were prepared in ultrahigh vacuum with the surface composition determined by low energy ion scattering. It was found that the activity of Ru towards the dissociative adsorption of methanol is a strong function of temperature. This change in the adsorptive nature of the Ru sites with temperature produced a variation in the optimum surface composition with temperature. The optimum surface had an Ru content which increased with increasing temperature, from close to ≈10 atomic percent (a/o) Ru at 25°C to a value in the vicinity of ≈30 a/o at 60°C. The shift in optimum composition with temperature was attributed to a shift in the rate‐determining step from methanol adsorption/dehydrogenation at low temperature to the surface reaction between the dehydrogenated intermediate and surface oxygen at high temperature. The apparent activation energies were consistent with this change in the rate‐determining step.
Electrochemical Heaters Utilizing Aluminum Alloy and Magnesium Anodes
Authors: Gilman S. , Bramhall P.
Published: June 2006

A short‐circuited electrochemical cell made with a saline electrolyte, an aluminum alloy or magnesium anode, and a manganese dioxide cathode may be used as a rather efficient short‐term portable heater. The use of a magnesium anode provides somewhat higher heat content but results in the production of considerable hydrogen gas. Certain aluminum‐zinc alloys are almost as energetic as magnesium and produce little hydrogen.
Cyclical Mastalgia and Breast Cancer Risk: Results of A French Cohort Study
Authors: Plu-Bureau Geneviève , Lê Monique G. , Sitruk-Ware Regine , Thalabard Jean-Christophe
Published: June 2006

Cyclical mastalgia is a common complaint, with a potentially important relationship to breast cancer risk. In the last decade, case-control studies have reported that cyclical mastalgia could be considered as an independent risk factor for breast cancer. The subjectivity of a retrospectively collected symptom questioned the validity of this finding. We have examined the association between cyclical mastalgia and breast cancer risk in the French cohort study of women with benign breast disease diagnosed in two breast clinics between 1976 and 1979 and followed-up until 1997. The present study was restricted to the women free of any hormonal treatment (n = 247). The mean follow-up was 16 ± 5 years, and a total of 22 breast cancers occurred during the follow-up. Using a Cox model with duration of cyclical mastalgia as a time-varying variable, the adjusted relative risk of breast cancer increased with the duration of cyclical mastalgia (P = 0.006). The corresponding relative risk for 37 months of cyclical mastalgia was 5.31 (95% confidence interval, 1.92-14.72). We show here that the conclusion still holds when the symptom cyclical mastalgia was collected prospectively in a cohort study, bringing additional evidence that cyclical mastalgia may represent an independent and useful clinical marker of increased breast cancer risk. It might be a confounding factor when assessing the effects of hormonal treatments on breast cancer risk such as hormonal replacement therapy or oral contraceptives. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1229–31)
Circulating Insulin-Like Growth Factor-I and Binding Protein-3 and Risk of Prostate Cancer
Authors: Severi Gianluca , Morris Howard A. , MacInnis Robert J. , English Dallas R. , Tilley Wayne D. , Hopper John L. , Boyle Peter , Giles Graham G.
Published: June 2006

Some recent epidemiologic studies have failed to confirm positive associations between insulin-like growth factor-I (IGF-I) and the risk of prostate cancer observed in earlier studies but have reported suggestive evidence for a positive association between IGF-binding protein-3 (IGFBP-3) and prostate cancer risk, a result contradicting the earlier assumption that high levels of IGFBP-3 would be protective against prostate cancer. We tested the association between IGF-I and IGFBP-3 and prostate cancer risk by measuring the two peptides in plasma samples collected at baseline in a prospective cohort study of 17,049 men. We used a case-cohort design, including 524 cases diagnosed during a mean of 8.7 years follow-up and a randomly sampled subcohort of 1,826 men. The association between each peptide level and prostate cancer risk was tested using Cox models adjusted for country of birth and alcohol consumption. The risk of prostate cancer was not associated with baseline levels of IGF-I or the molar ratio IGF-I/IGFBP-3 (all odds ratios are between 0.82 and 1.08; Ptrend ≥ 0.2), whereas the risk increased with baseline levels of IGFBP-3 (Ptrend = 0.008), the hazard ratio (HR) associated with a doubling of the concentration of IGFBP-3 being 1.70 (95% confidence interval, 1.15-2.52). The HR for quartile 4 relative to quartile 1 of IGFBP-3 was 1.49 (95% confidence interval, 1.11-2.00). The HRs did not differ by tumor aggressiveness or age at onset (all Ps ≥ 0.4). In our study, high levels of IGFBP-3 but not IGF-I were associated with an increased risk of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1137–41)
Population-Based Case-Control Study of VEGF Gene Polymorphisms and Breast Cancer Risk among Chinese Women
Authors: Kataoka Nobuhiko , Cai Qiuyin , Wen Wanqing , Shu Xiao-Ou , Jin Fan , Gao Yu-Tang , Zheng Wei
Published: June 2006

Vascular endothelial growth factor (VEGF) is a major angiogenic factor involved in a number of pathologic processes, including neovascularization, a crucial step in the development of solid malignancies. Using data and specimens collected in the Shanghai Breast Cancer Study, a population-based case-control study conducted in urban Shanghai, China from 1996 to 1998, we evaluated the association of VEGF gene polymorphisms with breast cancer risk. Included in this study were 1,093 cases and 1,184 age-matched controls who had completed an in-person interview and donated a blood sample to the study. Polymorphisms in the promoter region (T−460C), 5′ untranslated region (C+405G), and 3′untranslated region (C936T) were genotyped using the Taqman allelic discrimination assay. No statistically significant case-control difference was found for the C+405G and T−460C polymorphisms. However, the C936T polymorphism was associated with a reduced risk of breast cancer. Compared with CC genotype carriers, women who had the TT genotype showed a decreased risk [odds ratio (OR), 0.65; 95% confidence interval (95% CI) 0.41-1.02], and the inverse association was restricted to premenopausal women (OR, 0.45; 95% CI, 0.25-0.79). Six common haplotypes were identified. Compared with the most common haplotype (−460T/405C/936C), the −460T/405G/936T haplotype was associated with a reduced risk of breast cancer (OR, 0.67; 95% CI, 0.43-1.04), particularly in premenopausal women (OR, 0.47; 95% CI, 0.27-0.81). Our study suggests that the VEGF C936T polymorphism might be a susceptibility factor for breast cancer among Chinese women. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1148–52)
Barriers to Full Colon Evaluation for a Positive Fecal Occult Blood Test
Authors: Fisher Deborah A. , Jeffreys Amy , Coffman Cynthia J. , Fasanella Kenneth
Published: June 2006

Background: Failure to appropriately evaluate a positive cancer screening test may negate the value of doing that test. The primary aim of this study was to explore the factors associated with undergoing a full colon evaluation for a positive fecal occult blood test (FOBT) in a single Veterans Affairs center.

Methods: Medical records of consecutive patients ages ≥50 years, who had a positive screening FOBT from March 2000 to February 2001, were abstracted. Patient demographics, dates of ordering and doing follow-up test(s), and adherence with scheduled procedures were collected. The primary outcome, full colon evaluation, was defined as having a colonoscopy or double-contrast barium enema plus flexible sigmoidoscopy completed within 12 months.

Results: The sample (N = 538) was 98% men (58% Caucasian, 29% African-American, and 13% unknown race). Approximately 77% of the patients were referred to gastroenterology. Ultimately, only 44% underwent full colon evaluation within 12 months. Approximately 20% of the patients failed to attend a scheduled procedure. Referral to gastroenterology and adherence to follow-up appointments were associated with full colon evaluation. There was no association between African-American versus Caucasian race and full colon evaluation.

Conclusions: Less than half of the patients with a positive FOBT had a full colon evaluation within 12 months. Multiple failures were identified, including lack of referral for further testing and patient nonadherence. Although the overall performance in evaluating a positive colorectal cancer screening test was poor, no racial disparity was observed. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1232–5)
Smoking and Smokeless Tobacco-Associated Human Buccal Cell Mutations and Their Association with Oral Cancer—A Review
Authors: Proia Nicole K. , Paszkiewicz Geraldine M. , Sullivan Nasca Maureen A. , Franke Gail E. , Pauly John L.
Published: June 2006

Reported herein are the results of a structured literature review that was undertaken to (a) determine if human buccal (mouth) cell changes are associated with smoking and smokeless (“chewing”) tobacco, (b) tabulate different buccal cell alterations that have been reported, (c) delineate buccal cell assays that have been used successfully, (d) determine whether buccal cell changes correlate with oral cancer as defined in clinicopathologic investigations, and (e) assess the feasibility of developing a high-throughput buccal cell assay for screening smokers for the early detection of oral cancer. The results of the studies reported herein have established that diverse buccal cell changes are associated with smoking and smokeless tobacco. This review documents also that buccal cells have been collected in a noninvasive manner, and repetitively for serial studies, from different sites of the mouth (e.g., cheek, gum, and tongue) and from normal tissue, preneoplastic lesions (leukoplakia), and malignant tumors. Tobacco-associated genetic mutations and nongenetic changes have been reported; a partial listing includes (a) micronuclei, (b) bacterial adherence, (c) genetic mutations, (d) DNA polymorphisms, (d) carcinogen-DNA adducts, and (e) chromosomal abnormalities. Clinical studies have correlated buccal cell changes with malignant tumors, and some oral oncologists have reported that the buccal cell changes are practical biomarkers. Summarily, the literature has established that buccal cells are useful not only for characterizing the molecular mechanisms underlying tobacco-associated oral cancers but also as exfoliative cells that express diverse changes that offer promise as candidate biomarkers for the early detection of oral cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1061-77)
Serum Cotinine Level as Predictor of Lung Cancer Risk
Authors: Boffetta Paolo , Clark Sarah , Shen Min , Gislefoss Randi , Peto Richard , Andersen Aage
Published: June 2006

Background: No prospective studies are available on serum cotinine level as a marker of lung cancer risk.

Methods: We analyzed serum cotinine level among 1,741 individuals enrolled since the 1970s in a prospective study of Norwegian volunteers who developed lung cancer during the follow-up and 1,741 matched controls free from lung cancer. Serum cotinine was measured with a competitive immunoassay. Regression dilution was corrected for based on repeated measures on samples from 747 subjects.

Results: Mean serum cotinine level was higher in cases than in controls. Compared with subjects with a cotinine level of ≤5 ng/mL, the odds ratio of lung cancer was increasing linearly, reaching 55.1 (95% confidence interval, 35.7-85.0) among individuals with a serum cotinine level of >378 ng/mL. There was no clear suggestion of a plateau in risk at high exposure levels. Odds ratios were very similar in men and women. We found no association between serum cotinine level (range, 0.1-9.9 ng/mL) and lung cancer risk among self-reported nonsmokers and long-term quitters (79 cases and 350 controls).

Discussion: The association between tobacco smoking and lung cancer risk might be stronger than is estimated from questionnaire-based studies. Serum cotinine level is a predictor of risk of lung cancer among smokers. The reported plateau in risk at high doses is likely due mainly to artifacts. There is no difference between men and women in the carcinogenicity of tobacco smoking. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1184–8)
Inflammation-Related Gene Polymorphisms and Colorectal Adenoma
Authors: Gunter Marc J. , Canzian Federico , Landi Stefano , Chanock Stephen J. , Sinha Rashmi , Rothman Nathaniel
Published: June 2006

Chronic inflammation has been reported to be a risk factor for colorectal neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with colorectal adenoma, a precursor of colorectal cancer. We investigated the association of colorectal adenoma with 19 single nucleotide polymorphisms in a range of important proinflammatory (IL1B, IL6, IL8, TNF, and LTA) and anti-inflammatory (IL4, IL10, and IL13) cytokines and other inflammation-related genes (PTGS2 and PPARG) in a case-control study of risk factors for colorectal polyps in which all participants (ages 18-74 years) had undergone colonoscopy or sigmoidoscopy. The study sample comprised 244 cases of colorectal adenoma and 231 polyp-free controls. Compared with being homozygous for the common allele, heterozygosity at the IL1B −31 (C>T) locus was associated with an odds ratio (OR) for colorectal adenoma of 1.8 [95% confidence interval (95% CI), 1.2-2.9]. Homozygous carriers of the IL8 −251-A allele were at 2.7-fold increased risk of adenoma (95% CI, 1.5-4.9) compared with homozygosity for the common T allele, whereas carriage of at least one IL8 −251-A allele conferred a 1.5 increased odds of disease (95% CI, 1.0-2.4). Among non–nonsteroidal anti-inflammatory drug users, there was a statistically significant association between the IL10 −819-T/T genotype and adenoma compared with the common IL10 −819-C/C genotype (OR, 3.9; 95% CI, 1.1-13.6), which was not evident among nonsteroidal anti-inflammatory drug users (OR, 0.7; 95% CI, 0.3-1.5; Pinteraction = 0.01). These exploratory data provide evidence that polymorphic variation in genes that regulate inflammation could alter risk for colorectal adenoma. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1126–31)
Macrophage Inhibitory Cytokine-1 H6D Polymorphism, Prostate Cancer Risk, and Survival
Authors: Hayes Vanessa M. , Severi Gianluca , Southey Melissa C. , Padilla Emma J.D. , English Dallas R. , Hopper John L. , Giles Graham G. , Sutherland Robert L.
Published: June 2006

Macrophage inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor-β superfamily, is important in regulating inflammation. Inflammation of the prostate has been suggested to favor tumor development. A recent study (JNCI 2004, 96:1248-1254) found marginal evidence of an association between the presence of the mature MIC-1 protein nonsynonymous polymorphism H6D C-to-G (rs1058587) with reduced prostate cancer risk [odds ratio, 0.83; 95% confidence interval (95% CI), 0.69-0.99]. We tested this in a population-based study of 819 cases and 731 controls from Australia and found a similar, yet not significant, odds ratio of 0.85 (95% CI, 0.7-1.04; P = 0.11). We also tested the potential association between the H6D variant and disease-specific survival in 640 cases followed-up for an average of 8.2 years. We found that cases carrying the H6D G allele had an increased risk of death from prostate cancer than cases carrying two copies of the C allele (hazard ratio, 1.72; 95% CI, 1.06-2.78; P = 0.03). Our data suggest that the H6D variant in MIC-1 might play a role in prostate cancer, but it is difficult to explain how a variant can be associated with lower risk of developing prostate cancer but more aggressive growth if cancer develops. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1223–5)
A Survey of Thromboprophylaxis Management in Patients with Major Trauma
Authors: Imberti Davide , Ageno Walter
Published: June 2006

Background: Venous thromboembolism (VTE) is a common life-threatening complication of major trauma. Although clinical guidelines clearly suggest routine VTE prevention with low-molecular-weight heparin (LMWH) in this specific group of patients, there is still a lack of strong recommendations regarding the timing and the modality of heparin administration and the role of mechanical prophylaxis. We tested the hypothesis that there is significant practice variation in thromboprophylaxis management of patients with major trauma among intensive care unit (ICU) specialists. Methods: Two hundred Italian ICU specialists, representing 200 ICU throughout the country, were contacted by telephone and were asked (1) whether they routinely prescribe pharmacological antithrombotic prophylaxis in patients with major trauma, whether prophylaxis is prescribed to all patients or to selected patients, and the type of prophylaxis and the timing of administration and (2) whether they recommend physical prevention, whether this is prescribed to all patients or to selected patients, and the type of physical prophylaxis. Results: In patients with major trauma, 85% of the interviewed ICU specialists answered that they prescribe pharmacological prophylaxis for VTE. 37.6% of them prescribe prophylaxis only to selected patients based on the level of risk, 87.7% prescribe low-molecular-weight heparin, and 42.4% start prophylaxis immediately after hospitalization. Only 61% of the interviewed specialists prescribe physical prophylaxis; 82.8% of them use elastic stockings, 9.8% intermittent pneumatic compression, and 7.4% other mechanical devices. Physical prophylaxis is prescribed to all patients by 41%, and by 59% only in case of contraindication to pharmacological prevention. Inferior vena cava (IVC) filter insertion is considered by 47% when anticoagulation is contraindicated; 91.4% of them recommend the IVC filter only if deep vein thrombosis (DVT) has been diagnosed. Conclusions: Even when there are clinical guidelines, prescription of VTE prevention in patients with major trauma is underused and timing and modality of prophylaxis are rather heterogeneous. When anticoagulation is contraindicated, IVC filters are commonly recommended only in the presence of DVT.
Combinations of Low Doses of Unfractionated Heparin and of Low-Molecular-Weight Heparin Prevent Experimental Venous Thrombosis
Authors: Carelli Guareide , Maffei Francisco H.A. , Mattar Luci , Ferrari Iracema C. , Thomazini-Santos Izolete A. , de Carvalho Lídia R.
Published: June 2006

Synergism between low-molecular-weight heparin and low doses of unfractionated heparin (UH) enhancing anti-factor Xa activity and the release of tissue factor pathway inhibitor was observed. The aim of this study was to verify whether this association is effective in preventing experimental venous thrombosis. Seventy rats were allocated into 7 groups: the control group treated with distilled water, the H350 group treated with UH 350 IU/kg, the E2 group treated with enoxaparin 2 mg/kg, the H175 group treated with UH 175 IU/kg, the E1 group treated with enoxaparin 1 mg/kg, the H175 + E1 group treated with UH 175 IU/kg plus enoxaparin 1 mg/kg, and the H100 + E0.5 group treated with UH 100 IU/kg plus enoxaparin 0.5 mg/kg. Forty minutes after subcutaneous injection, thrombosis was induced in vena cava. Three hours later, if present, thrombi were withdrawn and weighed. Bleeding time, activated partial thromboplastin time, thrombin time (TT), and anti-factor Xa were measured at the beginning and end of the experiment. Forty-eight other animals were treated, but without inducing thrombus, and tests were performed 40 min after injection. Thrombus developed in 90.9% of control animals, 20% of the H350 group, 22.2% of the E2 group, 10% of the H175 + E1 group, and 30% of the H100 + E0.5 group; there was a difference between group C and the other groups. Only in the H350 and H175 + E1 groups were TT and activated partial thromboplastin time prolonged in relation to control at the end of the experiment. Forty minutes after injection, TT was prolonged in the H350 and H175 + E1 groups. In conclusion, combinations of low doses of low-molecular-weight heparin and low doses of UH were as effective as high doses of each one used alone in preventing thrombus development in rat vena cava.
Evaluation of Platelet Indexes in Patients with Aortic Aneurysm
Authors: Ihara Akihiro , Matsumoto Kengo , Kawamoto Toshiharu , Shouno Saburou , Kawamoto Jun , Katayama Akira , Yoshitatsu Masao , Izutani Hironori
Published: June 2006

The purpose of this study was to investigate whether platelet indexes [platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR), and platelet distribution width (PDW)] could serve as diagnostic tools to evaluate the potential significance of platelet heterogeneity on thrombus formation. Blood samples were obtained from 54 patients with aortic aneurysm (AA; mean age 73 years; 40 males, 14 females), from 120 age-matched controls (AC; mean age 74 years; 61 males, 59 females), and from 38 young controls (YC; mean age 30 years; 20 males, 18 females). We measured the blood platelet indexes using an automated counter, as well as plasma D-dimer and thrombin-antithrombin III complex (TAT) using ELISA. The AA patients were divided into two groups, group A (platelet count more than 150 × 109/l, n = 36) and group B (platelet count below 150 × 109/l, n = 18). There was no difference in the platelet count between AC and YC. However, P-LCR was significantly higher (p = 0.0113) in AC. MPV and PDW were also higher, but not significantly so. The platelet count was not different between group A and AC. MPV (p = 0.0024 and <0.0001, respectively), P-LCR (p < 0.0012 and <0.0001, respectively) and PDW (p = 0.0006 and 0.0005, respectively) were significantly lower in group A than in group B and AC. The platelet indexes were significantly lower in the 54 AA patients than in the AC. There were significant inverse relationships between the platelet count and other indexes in the AC and 54 AA patients; however, no relationships were observed in group A, B and YC. The D-dimer and TAT levels were significantly higher in group B than in groups A and YC. In conclusion, these findings suggest that large platelets decrease rather than increase in patients with AA.
Enalapril Reduces the Expression of Nuclear Factor-κB and c-Jun N-Terminal Kinase in the Renal Cortices of Five-Sixths-Nephrectomized Rats
Authors: Costa Joana C.S.R. , Costa Roberto S. , Silva Cleonice G.A. , Coimbra Terezila M.
Published: June 2006

Background/Aim: Five-sixths-nephrectomized rats present renal functional and histological abnormalities which are attenuated by enalapril treatment. c-Jun N-terminal kinase (JNK), a mitogen-activated protein kinase, and nuclear factor-ĸB (NF-ĸB) pathways can be activated by angiotensin II which has been implicated in renal injury. The aim of this study was to investigate the effect of enalapril on the expression of NF-ĸB and JNK in renal cortices of five-sixths-nephrectomized rats. Methods: Of the 65 rats studied, 25 underwent five-sixths nephrectomy and received no treatment, 15 underwent five-sixths nephrectomy and received enalapril, 15 were sham operated and received no treatment, and 10 were sham operated and received enalapril. On postoperative days 15 and 90, systolic blood pressure, glomerular filtration rate, and albumin excretion were determined. The rats were then killed and the kidneys removed for histology and immunohistochemistry. Results: In five-sixths-nephrectomized rats, we observed functional and structural renal alterations, as well as greater NF-ĸB/JNK expression and higher macrophage counts. Enalapril treatment reduced all of these changes. Conclusion: The protective effect of enalapril on the kidney of five-sixths-nephrec tomized rats might be related to the inhibition of NF-ĸB and JNK activation.
‘We shed tears, but there is no one there to wipe them up for us’: narratives of (mis)trust in a materially deprived community
Authors: Ward Paul , Coates Anna
Published: June 2006

This article reports on a qualitative study in a materially deprived locality in northern England, which originally aimed to explore local residents’ views of proposed changes to local health care provision. However, participants also quickly moved the research agenda onto widespread discussions of (mis)trust. Unlike much sociological literature that defines trust as operating on two levels (inter-personal and system-based), their narratives of trust were constructed on several inter-connected levels. We explore mistrust in local general practitioners (GPs) as a factor of mistrust of a number of local and national organizations and social systems, rather than solely related to the medical system. Widespread mistrust of ‘authority’ was narrated through a shared history of disinvestment and loss of services in the locality and ‘broken promises’ by a range of institutions, which precipitated feelings of social exclusion and disembeddedness
Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia
Authors: Scott Linda M. , Scott Mike A. , Campbell Peter J. , Green Anthony R.
Published: June 2006

An acquired V617F JAK2 mutation occurs in patients with polycythemia vera (PV) or essential thrombocythemia (ET). In a proportion of V617F-positive patients, mitotic recombination produces mutation-homozygous cells that come to predominate with time. However, the prevalence of homozygosity is unclear, as previous reports studied mixed populations of wild-type, V617F-heterozygous, and V617F-homozygous mutant cells. We therefore analyzed 1766 individual hematopoietic colonies from 34 patients with PV or ET in whom granulocyte sequencing demonstrated that the mutant peak did not predominate. V617F-positive erythroid burst-forming units (BFU-Es) were more frequent in patients with PV compared with patients with ET (P = .022) and, strikingly, V617F-homozygous BFU-Es were detected in all 17 patients with PV, but in none of the patients with ET (P < .001). Moreover, mutation-homozygous cells were present in 2 patients with ET after polycythemic transformation. These results demonstrate that V617F-homozygous erythroid progenitors are present in most patients with PV but occur rarely in those with ET.
High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6-deregulating mutations, in gastric lymphoma
Authors: Chen Yun-Wen , Hu Xiao-Tong , Liang Anthony C. , Au Wing-Yan , So Chi-Chiu , Wong Michelle L. , Shen Lijun , Tao Qian , Chu Kent-Man , Kwong Yok-Lam , Liang Raymond H. , Srivastava Gopesh
Published: June 2006

To investigate the role of BCL6 in the pathogenesis of gastric lymphoma, we analyzed the BCL6 promoter region for BCL6 translocations, somatic hypermutations, and deregulating mutations in 43 gastric lymphomas, including 4 extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas), 33 diffuse large B-cell lymphomas (DLBCLs), and 6 composite DLBCLs with residual MALT lymphoma (DLCLMLs). BCL6 promoter substitutions by immunoglobulin (Ig) and non-Ig translocation partners, resulting in its deregulation, were frequently involved in DLBCL (36.4%) and DLCLML (50%). Two novel BCL6 translocation partner genes, 28S rRNA and DMRT1, and a new BCL6 translocation breakpoint in intron 2 were also identified. Deregulating mutations were found only in DLBCL (24.2%), which correlated significantly with high BCL6 protein expression. Significantly, high BCL6 expression correlated strongly with longer overall survival (OS), independent of mechanism in gastric DLBCL and DLCLML. Gastric DLBCLs were further subclassified into germinal center B-cell–like (GCB) and non-GCB subgroups immunohistochemically. High BCL6 expression was detected in all GCB cases, irrespective of BCL6 genetic alterations. In the non-GCB subgroup, BCL6-deregulating mutations correlated significantly with high BCL6 expression level. No significant correlation was found between the BCL6 expression level and OS in the non-GCB subgroup, which had significantly poorer prognosis than the GCB subgroup.
Src family kinases are important negative regulators of G-CSF-dependent granulopoiesis
Authors: Mermel Craig H. , McLemore Morgan L. , Liu Fulu , Pereira Shalini , Woloszynek Jill , Lowell Clifford A. , Link Daniel C.
Published: June 2006

Granulocyte colony-stimulating factor (G-CSF) is the principal cytokine regulating granulopoiesis. Truncation mutations of the G-CSF receptor (G-CSFR) are associated with the development of acute myeloid leukemia in patients with severe congenital neutropenia. Although increased proliferative signaling by a representative G-CSFR truncation mutation (termed d715) has been documented, the molecular basis for this hyperproliferative phenotype has not been fully characterized. Given the accumulating evidence implicating Src family kinases in the transduction of cytokine receptor signals, the role of these kinases in the regulation of G-CSF signaling was examined. We show that Hck and Lyn, Src family kinases expressed in myeloid cells, are negative regulators of granulopoiesis that act at distinct stages of granulocytic differentiation. Whereas Hck regulates the G-CSF-induced proliferation of granulocytic precursors, Lyn regulates the production of myeloid progenitors. Interestingly, d715 G-CSFR myeloid progenitors were resistant to the growth-stimulating effect of treatment with a Src kinase inhibitor. Together, these data establish Lyn and Hck as key negative regulators of granulopoiesis and raise the possibility that loss of Src family kinase activation by the d715 G-CSFR may contribute to its hyperproliferative phenotype.
Genome Annotation Transfer Utility (GATU): rapid annotation of viral genomes using a closely related reference genome
Authors: Tcherepanov Vasily , Ehlers Angelika , Upton Chris
Published: June 2006

Background

Since DNA sequencing has become easier and cheaper, an increasing number of closely related viral genomes have been sequenced. However, many of these have been deposited in GenBank without annotations, severely limiting their value to researchers. While maintaining comprehensive genomic databases for a set of virus families at the Viral Bioinformatics Resource Center http://www.biovirus.org and Viral Bioinformatics – Canada http://www.virology.ca, we found that researchers were unnecessarily spending time annotating viral genomes that were close relatives of already annotated viruses. We have therefore designed and implemented a novel tool, Genome Annotation Transfer Utility (GATU), to transfer annotations from a previously annotated reference genome to a new target genome, thereby greatly reducing this laborious task.

Results

GATU transfers annotations from a reference genome to a closely related target genome, while still giving the user final control over which annotations should be included. GATU also detects open reading frames present in the target but not the reference genome and provides the user with a variety of bioinformatics tools to quickly determine if these ORFs should also be included in the annotation. After this process is complete, GATU saves the newly annotated genome as a GenBank, EMBL or XML-format file. The software is coded in Java and runs on a variety of computer platforms. Its user-friendly Graphical User Interface is specifically designed for users trained in the biological sciences.

Conclusion

GATU greatly simplifies the initial stages of genome annotation by using a closely related genome as a reference. It is not intended to be a gene prediction tool or a "complete" annotation system, but we have found that it significantly reduces the time required for annotation of genes and mature peptides as well as helping to standardize gene names between related organisms by transferring reference genome annotations to the target genome.

The program is freely available under the General Public License and can be accessed along with documentation and tutorial from http://www.virology.ca/gatu.
Painful rib hump: a new clinical sign for detecting intraspinal rib displacement in scoliosis due to neurofibromatosis
Authors: Gkiokas Andreas , Hadzimichalis Socratis , Vasiliadis Elias , Katsalouli Marina , Kannas Georgios
Published: June 2006

Background

Spinal cord compression and associate neurological impairment is rare in patients with scoliosis and neurofibromatosis. Common reasons are vertebral subluxation, dislocation, angulation and tumorous lesions around the spinal canal. Only twelve cases of intraspinal rib dislocation have been reported in the literature. The aim of this report is to present a case of rib penetration through neural foramen at the apex of a scoliotic curve in neurofibromatosis and to introduce a new clinical sign for its detection.

Methods

A 13-year-old girl was evaluated for progressive left thoracic kyphoscoliotic curve due to a type I neurofibromatosis. Clinical examination revealed multiple large thoracic and abdominal "cafe-au-lait" spots, neurological impairment of the lower limbs and the presence of a thoracic gibbous that was painful to pressure at the level of the left eighth rib (Painful Rib Hump). CT-scan showed detachment and translocation of the cephalic end of the left eighth rib into the adjacent enlarged neural foramen. The M.R.I. examination of the spine showed neither cord abnormality nor neurogenic tumor.

Results

The patient underwent resection of the intraspinal mobile eighth rib head and posterior spinal instrumentation and was neurologically fully recovered six months postoperatively.

Conclusion

Spine surgeons should be aware of intraspinal rib displacement in scoliotic curves in neurofibromatosis. Painful rib hump is a valuable diagnostic tool for this rare clinical entity.
Handling dropout and clustering in longitudinal multicentre clinical trials
Authors: Del Bianco P , Borgoni R
Published: June 2006

Many clinical trials enrol patients from different medical centres. Multi-centre studies are particularly helpful in cancer research as they allow researchers to evaluate the efficacy of a therapy in a variety of patients and settings, making it possible to investigate the effect of treatments in those cases when it is difficult, or even impossible, for a single centre to recruit the required number of patients. It is often argued, however, that despite agreement among different centres to follow common standardized protocols, variation may occur in both baseline characteristics of the recruited patients and in treatment effects. This heterogeneity should be detected and, if present, accounted for in the data analysis. Furthermore, the longitudinal nature of these types of experimental studies raises the problem of attrition, that is, patients may dropout of the study for a number of reasons mainly death or disease progression. In this paper, we consider the health related quality of life of advanced melanoma patients in a longitudinal multi-centre randomized clinical trial comparing two different anti-tumoural treatments. We propose a Heckman type model to account for the possibility that patients dropout according to a non-ignorable mechanism. The model is extended to a multilevel setting to account both for the longitudinal nature and the multi-centre structure of the design. We found a strong variation across centres in the quality of life evaluation. The effect of centres on the dropout was not found to be relevant in the considered data although dropout does depend on patient′s characteristics.
Synergistic effects of CoCl2 and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells
Authors: Pacary Emilie , Legros Hélène , Valable Samuel , Duchatelle Pascal , Lecocq Myriam , Petit Edwige , Nicole Olivier , Bernaudin Myriam
Published: June 2006

Bone-marrow-derived mesenchymal stem cells (MSCs) constitute an interesting cellular source to promote brain regeneration after neurodegenerative diseases. Recently, several studies suggested that oxygen-dependent gene expression is of crucial importance in governing the essential steps of neurogenesis such as cell proliferation, survival and differentiation. In this context, we analysed the effect of the HIF-1 (hypoxia inducible factor-1) activation-mimicking agent CoCl2 on MSCs. CoCl2 treatment increased the expression of the anti-proliferative gene BTG2/PC3 and decreased cyclin D1 expression. Expression of HIF-1α and its target genes EPO, VEGF and p21 was also upregulated. These changes were followed by inhibition of cell proliferation and morphological changes resulting in neuron-like cells, which had increased neuronal marker expression and responded to neurotransmitters. Echinomycin, a molecule inhibiting HIF-1 DNA-binding activity, blocked the CoCl2 effect on MSCs. Additionally, by using Y-27632, we demonstrated that Rho kinase (ROCK) inhibition potentiated CoCl2-induced MSC differentiation in particular into dopaminergic neuron-like cells as attested by its effect on tyrosine hydroxylase expression. Altogether, these results support the ability of MSCs to differentiate into neuron-like cells in response to CoCl2, an effect that might act, in part, through HIF-1 activation and cell-cycle arrest, and which is potentiated by inhibition of ROCK.
Some aspects of rat femorotibial joint microanatomy as demonstrated by high-resolution magnetic resonance imaging
Authors: Wang Y-X J , Bradley D P , Kuribayashi H , Westwood F R
Published: June 2006

High-resolution magnetic resonance images (MRI) of the right femorotibial joint of normal Han:Wistar rats were acquired using a 4.7 Tesla magnet and a single-turn solenoid radio frequency coil (built in-house). Some anatomical findings of the rat femorotibial joint, which have not been reported previously using MRI, are described. The separation of patellar ligament and crural fascia was feasible on MRI. This separation would not be seen on images of lower resolution and its presence on high-resolution images could be mistaken for artefact due to the magic angle effect. Band-like fibrous structures exist in the infra-patellar fat pad, which might be mistaken as ligaments within the femorotibial joint. On sagittal MRI a vessel was seen inserted on the central part of the caudal surface of the patellar ligament. Subcutaneous fascia/cutaneous muscles (panniculus carnosus) could also be demonstrated with MRI in the femorotibial joint area.
Endogena korupcija
Authors: Milovanovic Milic
Published: June 2006

The paper deals with a new form of corruption developed with the privatization process in transition economies. Prerequisites for this form of corruption are dispersed ownership claims, underdeveloped capital markets, feeble product competition, and managerial class willing to behave opportunistically. In all transition economies labor has a strong incentive to unionize in order to avoid restructuring and consequent loss of jobs. Managers, on their part, realize that under the stated conditions unionized labor may protect their position in the eventual confrontation with outside owners, so they promote friendly union leaders. Both sides find cooperative strategy strongly dominating the other possible ways of conduct. Consequently, managers give special privileges to union leaders, who turn their blind eye to managers' misconduct. Mutual benefits are financed at the expense of outside owners who are clear losers in this game. Starting with the public choice definition of corruption - as selling of ownership rights by an agent to a third party - this process is labeled as endogenous corruption. The endogenous corruption is clearly harmful since the combined gain by the parties involved is less than the loss in consumers' and producers' surpluses. The endogenous corruption deal remains unopposed due to the Olson's paradox, i.e. gains are concentrated and losses are broadly dissipated and consequently no countervailing action is taken. As usual anti-corruption strategies do not help, final section of the paper discuses potential remedies. .
Konzistentnost izbora metoda viseatributivne analize
Authors: Pavlicic Dubravka
Published: June 2006

In this paper we analyze the consistency of the results of Multi-Attribute Decision Making (MADM) methods. Two conditions of consistent choice are defined, due to change in units used for measuring different attributes, and due to framing of attributes (whether they are defined as benefit or as cost attributes, when both forms are possible and are normatively equivalent). It is shown by several examples that two popular MADM methods (SAW and TOPSIS) violate both conditions. We conclude that the main causes for inconsistent choices are: 1) normalization of data, conducted in the first step of the observed methods, and 2) the usage of Likert scales for measuring qualitative attributes. Finally, these conclusions are generalized to all MADM methods which are based on normalized ratings and which treat Likert scales as interval scales. .
Glasanje i drustveni izbor
Authors: Azdejkovic Dragan
Published: June 2006

The choice of a voting rule is one of the major ethical question with far-reaching implications on the behavior of the political and other institutions. In this paper we search for a practical voting rule that can be recommended from a certain theoretical aspect. We will study the properties of various voting rules from an axiomatic angle. When only two candidates are at stake, simple majority voting is unambiguously the fairest method. This principle is a benchmark for democratic decision making. We analyze voting for three or more candidates. What voting rule would properly extend majority voting among pairs? .
Visekriterijumska optimizacija izbora izvodjaca projekta
Authors: Vuleta Jovo
Published: June 2006

The selection of the best (multicriterial optimal) contractors for project realization is analised in this paper. This problem is one of the most important problems that occurs during the realization of every project, especially the complex one. First we point the problem importance and past experiences and results in its solving. As a conclusion, we state that the problem of selection project realization contractors has been solved by discovering any possible solution, not necessary the optimal one. We have tried to solve one real problem using the model of integer multicriterial optimization type 0-1. The problem was presented by the appropriate mathematical model whose solving leads to multicriterial optimal solution. The special attention was paid to technique and procedure for solving the given model of integer multicriterial optimization. In order to minimize the efforts, the model has been transformed in corresponding network model whose further solving is based on the theory of graphs. The presented procedure decreases the number of mathematical operations and is more simply than most of the usual methods for solving the integer multicriterial type 0-1 optimization problems. At the end, the recommended procedure has been illustrated by a numerical example.