bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible Mediators of Connecting Tubule Glomerular Feedback
Authors: Ren YiLin , D'Ambrosio Martin A. , Garvin Jeffrey L. , Wang Hong , Carretero Oscar A.
Published: December 2008

In the renal cortex, the connecting tubule (CNT) returns to the glomerular hilum and contacts the afferent arteriole (Af-Art). Increasing Na delivery to the CNT dilates the Af-Art by activating epithelial Na channels, a process that we call connecting tubule glomerular feedback (CTGF). However, the mediator(s) of CTGF are unknown. We tested the hypothesis that Na reabsorption by the CNT induces release of arachidonic acid metabolites that diffuse to and dilate the Af-Art. Microdissected rabbit Af-Arts and adherent CNTs were simultaneously microperfused. CTGF was measured as the increase in diameter of norepinephrine-preconstricted Af-Arts in response to switching NaCl concentration in the lumen of the CNT from 10 to 80 mmol/L. Under control conditions, CTGF was repeatable and completely reversed norepinephrine-induced vasoconstriction. In the presence of 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, CTGF was completely blocked (−0.7±0.3 versus 7.3±0.5 μm), suggesting that arachidonic acid metabolites mediate CTGF. Because both cyclooxygenase-derived prostaglandins and epoxygenase-derived epoxyeicosatrienoic acids are known vasodilatory arachidonic acid metabolites, we tested whether indomethacin or MS-PPOH (a cyclooxygenase and an epoxygenase inhibitor) could block CTGF. Both indomethacin and MS-PPOH partially blocked CTGF (2.3±0.8 versus 6.5±0.5 μm, and 2.9±0.8 versus 6.6±1.1 μm, respectively). When combined, they completely blocked CTGF (−0.4±0.3 versus 6.6±1.1 μm). We confirmed these findings by using the epoxyeicosatrienoic acid antagonist 14,15-EEZE. The combination of indomethacin plus 14,15-EEZE completely abolished CTGF (−0.3±0.2 versus 8.0±1.0 μm). We conclude that increasing Na concentrations in the CNT stimulate release of prostaglandins and epoxyeicosatrienoic acids, which mediate CTGF.
Response of Humidity and Clouds to Tropical Deep Convection
Authors: Zelinka Mark D. , Hartmann Dennis L.
Published: December 2008

Currently available satellite data can be used to track the response of clouds and humidity to intense precipitation events. A compositing technique centered in space and time on locations experiencing high rain rates is used to detail the characteristic evolution of several quantities measured from a suite of satellite instruments. Intense precipitation events in the convective tropics are preceded by an increase in low-level humidity. Optically thick cold clouds accompany the precipitation burst, which is followed by the development of spreading upper-level anvil clouds and an increase in upper-tropospheric humidity over a broader region than that occupied by the precipitation anomalies. The temporal separation between the convective event and the development of anvil clouds is about 3 h. The humidity increase at upper levels and the associated decrease in clear-sky longwave emission persist for many hours after the convective event. Large-scale vertical motions from reanalysis show a coherent evolution associated with precipitation events identified in an independent dataset: precipitation events begin with stronger upward motion anomalies in the lower troposphere, which then evolve toward stronger upward motion anomalies in the upper troposphere, in conjunction with the development of anvil clouds. Greater upper-tropospheric moistening and cloudiness are associated with larger-scale and better-organized convective systems, but even weaker, more isolated systems produce sustained upper-level humidity and clear-sky outgoing longwave radiation anomalies.
Parameter Sensitivity in LSMs: An Analysis Using Stochastic Soil Moisture Models and ELDAS Soil Parameters
Authors: Teuling Adriaan J. , Uijlenhoet Remko , van den Hurk Bart , Seneviratne Sonia I.
Published: December 2008

Integration of simulated and observed states through data assimilation as well as model evaluation requires a realistic representation of soil moisture in land surface models (LSMs). However, soil moisture in LSMs is sensitive to a range of uncertain input parameters, and intermodel differences in parameter values are often large. Here, the effect of soil parameters on soil moisture and evapotranspiration are investigated by using parameters from three different LSMs participating in the European Land Data Assimilation System (ELDAS) project. To prevent compensating effects from other than soil parameters, the effects are evaluated within a common framework of parsimonious stochastic soil moisture models. First, soil parameters are shown to affect soil moisture more strongly than the average evapotranspiration. In arid climates, the effect of soil parameters is on the variance rather than the mean, and the intermodel flux differences are smallest. Soil parameters from the ELDAS LSMs differ strongly, most notably in the available moisture content between the wilting point and the critical moisture content, which differ by a factor of 3. The ELDAS parameters can lead to differences in mean volumetric soil moisture as high as 0.10 and an average evapotranspiration of 10%–20% for the investigated parameter range. The parsimonious framework presented here can be used to investigate first-order parameter sensitivities under a range of climate conditions without using full LSM simulations. The results are consistent with many other studies using different LSMs under a more limited range of possible forcing conditions.
On the Correction of Partial Beam Blockage in Polarimetric Radar Data
Authors: Lang Timothy J. , Nesbitt Stephen W. , Carey Lawrence D.
Published: December 2008

Three methodologies for correcting the radar reflectivity factor (ZH) in the presence of partial beam blockage are implemented, compared, and evaluated using a polarimetric radar dataset from the North American Monsoon Experiment (NAME) in northwestern Mexico. One methodology uses simulated interactions between radar beams and digital terrain maps, while the other two invoke the self-consistency of polarimetric radar measurands in rainfall, and the relative insensitivity of a specific differential phase to beam blockage. While the different methodologies often agree to within 1–2 dB, significant disagreements can occur in regions of sharp azimuthal gradients in beam blockage patterns, and in areas where the terrain-caused radar clutter map is complex. These disagreements may be mitigated by the use of additional radar data to develop the polarimetric correction techniques, by a more sophisticated terrain-beam interaction model, or by a higher-resolution digital terrain map. Intercomparisons between ground radar data and Tropical Rainfall Measuring Mission satellite overpasses suggest that all of the methodologies can correct mean ZH to within the expected uncertainty of such intercomparisons (1–1.5 dB). The polarimetric correction methods showed good results even in severely blocked regions (>10 dB reduction). The results suggest the possibility that all of the techniques may be valid approaches to correcting partial beam blockage, and within that context relative advantages and disadvantages of each technique are discussed. However, none of the techniques can correct radar data when weak echoes are reduced to noise by strong blocks, thus leading to biases in corrected ZH and rainfall climatologies.
A Variational Method for Computation of Sensible Heat Flux over the Arctic Sea Ice
Authors: Cao Zuohao , Ma Jianmin
Published: December 2008

In this study, a variational approach was employed to compute surface sensible heat flux over the Arctic sea ice. Because the variational approach is able to take into account information from the Monin–Obukhov similarity theory (MOST) as well as the observed meteorological information, it is expected to improve the pure MOST-based approach in computation of sensible heat flux. Verifications using the direct eddy-correlation measurements over the Arctic sea ice during the Surface Heat Budget of the Arctic Ocean (SHEBA) experiment period of 1997/98 show that the variational method yields good agreement between the computed and the measured sensible heat fluxes. The variational method is also shown to be more accurate than the traditional MOST method in the computation of sensible heat flux over the Arctic sea ice.
A Comparison of Variational and Ensemble-Based Data Assimilation Systems for Reanalysis of Sparse Observations
Authors: Whitaker Jeffrey S. , Compo Gilbert P. , Thépaut Jean-Noël
Published: December 2008

An observing system experiment, simulating a surface-only observing network representative of the 1930s, is carried out with three- and four-dimensional variational data assimilation systems (3D-VAR and 4D-VAR) and an ensemble-based data assimilation system (EnsDA). It is found that 4D-VAR and EnsDA systems produce analyses of comparable quality and that both are much more accurate than the analyses produced by the 3D-VAR system. The EnsDA system also produces useful estimates of analysis error, which are not directly available from the variational systems.
Talking Europe — the Dilemma of Sovereignty and Modernization
Authors: Braun Mats
Published: December 2008

There is a significant amount of scholarly literature produced on the topic of the alleged legitimacy deficit of the European Union (EU). This article is based on the assumption that the legitimacy of the EU is shaped largely by the domestic discourses on European governance. Therefore the stories of the individual countries are crucial for our understanding of EU legitimacy as a whole. The article is an analysis of how the legitimacy of the EU is constructed and shaped in the Czech and Swedish political discourses. It is based on discourse analysis and the constant comparative method of grounded theory, and suggests that the discourses on European unity in the two countries are structured around the nexus of modernization and sovereignty. Based on different constellations of this nexus, three ideal types are outlined: sovereignty unchallenged, sovereignty challenged and modernization unchallenged. In conclusion, it is suggested that the EU has been legitimized primarily as an instrument for modernization. Critics, however, base their argumentation on an underlying discourse on the sovereign people and on an understanding of the EU as a hindrance to progress. The advocates thus emphasize output-oriented legitimacy, while the critics are more concerned with input-based legitimacy.
National Performance Mandates and Intergovernmental Collaboration
Authors: Stalebrink Odd J.
Published: December 2008

This exploratory research is aimed at offering insights into how intergovernmental dependencies influence Program Assessment Rating Tools (PART) ratings under circumstances when federal funds and responsibility are delegated downward in the system. The research offers formal support for the hypothesis that programs carried out under such circumstances score relatively lower on those portions of the PART instrument that are dependent on intergovernmental collaboration. The findings are important in that they draw attention to an opportunity to improve the consistency of PART ratings across programs. Specifically, they suggest that it may be necessary to revise the instrument to include questions that recognizes and gives credit to efforts of intergovernmental collaborative efforts as part of the PART scoring process.
A Community-Based Participatory Critique of Social Isolation Intervention Research for Community-Dwelling Older Adults
Authors: Sabir Myra , Wethington Elaine , Breckman Risa , Meador Rhoda , Reid M.C. , Pillemer Karl
Published: December 2008

This article examines the dialogue that occurred within the structure of a Research-to-Practice Consensus Workshop that critiqued academic research priorities regarding social isolation among community-dwelling older adults and identified practice-based suggestions for a social isolation research agenda. The investigators adapted the scientific consensus workshop model to include expert practitioners and researchers in a discussion of the current state and future directions of social isolation intervention research. The group's critique resulted in several key recommendations for future research including the need for a social isolation measure with specific capacity to identify isolated older adults during a community crisis. This study demonstrates that the Research-to-Practice Consensus Workshop model can be used successfully to identify priority areas for research that have implications for community practice, construct an evidence base more relevant for community application, strengthen existing community—researcher partnerships, and build agency and practitioner capacity to take part in community-based participatory research.
Late-Life Volunteering and Trajectories of Physical Health
Authors: Tang Fengyan
Published: December 2008

The purpose of this study was to examine the longitudinal relationship between volunteering engagement and trajectories of physical health. Using three-wave panel data from the Americans' Changing Lives survey, the author tested the association between volunteering engagement and physical health after controlling for health variables from previous waves. Volunteering engagement was measured through volunteer status and hours. Physical health was measured through self-rated health, functional dependency, and chronic conditions. Findings indicated that volunteering engagement was associated with improved self-rated health and decreased functional dependency but not with the number of chronic conditions. Volunteering is a social approach to health maintenance in the older population, and the findings of this study add to the literature suggesting that volunteering probably leads to positive outcomes, but the relationship is also related to resource, status, and network variables.
Attraction to Organizational Culture Profiles
Authors: Gardner William L. , Reithel Brian J. , Foley Richard T. , Cogliser Claudia C. , Walumbwa Fred O.
Published: December 2008

Today's organizations are challenged with attracting, developing, and retaining high-quality employees; thus, many firms seek to improve their recruitment and selection processes. One approach involves using realistic job previews (RJPs) to communicate a balanced view of the organization. The authors explored the effects of organizational culture (hierarchy, market, clan, and adhocracy), recruitment strategy (RJP vs. traditional), and personality (horizontal and vertical individualism—collectivism) on attraction to Web-based organizational profiles using a sample of 234 undergraduate students in a mixed two-factor experimental design. Results indicate that the clan culture is viewed as the most attractive. Traditional versus RJP recruitment produced higher levels of organizational attraction. Finally, predicted relationships between the personality framework of horizontal and vertical individualism— collectivism and organizational attraction were supported.
States’ Compliance with International Requirements
Authors: Avdeyeva Olga
Published: December 2008

The article explores government compliance with international pressures measured as policy adoption and institutional reform. The findings reveal that government compliance is determined by the domestic political system and depends on the configuration of political actors mobilized in support of reform. Legislative reform is facilitated by a strong women’s movement and mobilized female parliamentarians. Institutional reform depends on the strength of the women’s movement and its ability to form coalitions with political actors within government elites, most importantly governing parties. Finally, the effect of women’s movements’ actors on the institutional reform is moderated by the ideology of political parties in power.
The Relationship Between Super Users' Attitudes and Employee Experiences With Clinical Information Systems
Authors: Halbesleben Jonathon R. B. , Wakefield Douglas S. , Ward Marcia M. , Brokel Jane , Crandall Donald
Published: December 2008

The purpose of this study is to examine the manner in which Super User attitudes toward clinical information systems (CIS) are associated with employee experiences with CIS implementation. Super Users ( N = 82), selected by hospital administration to assist in implementation of the new CIS, completed a survey that assessed time spent in the Super User role as well as attitudes toward the role. These data were matched with hospital employee ( N = 325) survey data about attitudes toward CIS and its impact on work processes. Time spent in the role of Super User was associated with employee attitudes; Super Users' perceptions about qualifications also predicted employee attitudes, particularly about care outcomes and perceptions about implementation of the CIS. The study suggests that as organizations encourage more time in the Super User role and develop more positive attitudes about this role, the possibility of positive employee attitudes toward CIS increases.
Polyvictimization, Childhood Victimization, and Psychological Distress in College Women
Authors: Richmond Jessica M. , Elliott Ann N. , Pierce Thomas W. , Aspelmeier Jeffery E. , Alexander Apryl A.
Published: December 2008

Two studies examined the relationships among polyvictimization (i.e., high cumulative levels of victimization), six categories of childhood victimization (i.e., property crime, physical assault, peer/sibling, witnessed/indirect, sexual, and child maltreatment), and current psychological symptomatology in college females. Results indicated that exposure to multiple types of childhood victimization is common. Regression analyses revealed that polyvictimization accounted for a significant proportion of variability in scores for psychological distress beyond that accounted for by any victimization category alone. Moreover, the six categories separately accounted for little to no variability beyond that accounted for by polyvictimization. Finally, polyvictimization accounted for a significant proportion of variability in scores for psychological distress, beyond that already accounted for through the simultaneous entry of all six categories of victimization. Findings reiterate the importance for clinicians and researchers to comprehensively assess multiple categories of childhood victimization and polyvictimization and provide preliminary evidence that the total number of lifetime victimizations is at least as important, if not more important, than individual categories of victimization in predicting psychological distress.
Formation, exfoliation and restacking of MoS2 nanostructures
Authors: Hu K. H. , Hu X. G.
Published: December 2008

MoS2 nanostructures were prepared by heating MoS3 precursors which were synthesised by acidifying the mixed solution of Na2MoO4 and Na2S or CH3CSNH2 (TAA). The formation mechanism and exfoliation restacking behaviours of the obtained MoS2 nanostructures were investigated. The MoS3 precursor prepared from TAA was composed of hollow nanoballs while that from Na2S comprised microsized particles. Heating the obtained MoS3 hollow nanoballs under H2 at 780°C led to MoS2 hollow nanoballs. Owing to high temperatures decreased the layer space of MoS2, MoS2 nanoballs were changed into polyhedral structures at 960°C. However, calcining the prepared MoS3 microsized particles resulted in MoS2 nanoplatelets both at 780 and 960°C. The prepared MoS2 nanoballs could exfoliate only partly by the exfoliation technology because of their chemical stability. However, MoS2 nanoplatelets exfoliated completely in exfoliation treatment and formed nano-MoS2 monolayer suspension. The restacked production of the obtained nano-MoS2 monolayer suspension represented similar XRD characteristic with exfoliated nano-MoS2. This indicated that nano-MoS2 monolayers did not restack regularly along c axis.
Numerical simulation of bubble size distribution of aluminium foams in liquid state
Authors: Li K. , Xie M. Z. , Liu H.
Published: December 2008

A mathematical model for predicting the evolution of bubble size distribution in Al foams is presented, which takes into account effects of both the coarsening due to gas diffusion between bubbles and the liquid drainage. A bubble size distribution equation and a one-dimensional drainage equation are solved coupledly by a finite difference approach. Comparison with experimental results from the literature shows a general agreement. The model predictions indicate that the bubble size increases exponentially with time that is in good agreement with MacPherson's theory. Furthermore, computational results reveal that bubble size distributions are dependent strongly on the drainage behaviour, the Henry constant, gas diffusivity and surface tension of the Al foam in liquid state.
Calculation of transient nucleation rate for Pd and Zr based metallic glass alloys
Authors: Li H. Q. , Yan J. H. , Xu J. G.
Published: December 2008

In order to investigate the glass forming ability, a new method to evaluate the transient nucleation rate of glass alloys is provided in the present paper using the parameters of bulk metallic glasses, such as onset melting temperature, glass transition temperature, viscosity and the cooling rate. The transient nucleation rates of Au81Si19, Pd75Si25 and Zr–Al–Ni–Cu alloys are obtained with this method. The computing result for Au81Si19 agrees well with that of the literature. The results show that with increasing viscosity or cooling rate, the nucleation rate drops sharply. When the cooling rate reaches to 103 K s–1, the peak value of nucleation rate of Pd75Si25 falls to 104 mol–1 s–1. Under the cooling rate of 102·5 K s–1, the peak value of nucleation rate of Zr66Al9Ni9Cu16 decreases to 105 mol–1 s–1. To Zr66Al8Cu7Ni19, Zr66Al8Cu12Ni14, Zr66Al9Cu16Ni9 and Zr65Al7·5Cu17·5Ni10 alloys, with increasing content of Cu, the supercooled liquid region Δ Tx rises and the nucleation rate falls gradually.
Influence of section size on dual phase ADI microstructure and properties: Comparison with fully ferritic and fully ausferritic matrices
Authors: Basso A. , Martínez R. , Sikora J.
Published: December 2008

The present work aims to evaluate and compare the influence that section size has on the microstructure and properties of fully ferritic, fully ausferritic and dual phase ADI matrices. Samples taken from ‘Y’ blocks of 25, 50 and 75 mm thickness were used to perform metallographic studies and mechanical tests. Cooling rate differences arising from changes in section size promote different microsegregation characteristics affecting solid state transformations and, consequently, the final microstructure and properties.

When the section size increases, some properties decrease. The strongest deleterious effect was ascribed to the elongation and impact of ADI samples, where drops of nearly 40% were reached when specimens taken from the thinnest ‘Y’ blocks were compared to those taken from the thickest ones. Regarding fracture toughness, ferritic matrices exhibited the most noticeable detrimental effect. Dual phase ADI samples, on the other hand, presented the least deleterious section size effect on all the studied properties.
Transformation texture of allotriomorphic ferrite in steel
Authors: Kim D. W. , Qin R. S. , Bhadeshia H. K. D. H.
Published: December 2008

Many aspects of the crystallographic texture which develops when austenite transforms into martensite or bainite are well established because the process by which the parent lattice is transformed into that of the product is mathematically defined. This is not the case when the ferrite forms by a reconstructive mechanism. The allotriomorphic ferrite nucleates heterogeneously at austenite grain boundaries, and although a reproducible, low energy orientation relationship is expected to exist between the ferrite and one of the austenite grains with which it is in contact, there are reports that the ferrite can simultaneously adopt this orientation with more than one austenite grain. The authors examine this possibility using crystallographic theory in order to assess the probability of such events as a function of the strength of the texture within the austenite before its transformation.
Clonal analysis of deletions on chromosome 20q and JAK2-V617F in MPD suggests that del20q acts independently and is not one of the predisposing mutations for JAK2-V617F
Authors: Schaub Franz X. , Jäger Roland , Looser Renate , Hao-Shen Hui , Hermouet Sylvie , Girodon François , Tichelli Andre , Gisslinger Heinz , Kralovics Robert , Skoda Radek C.
Published: December 2008

We developed a real-time copy number polymerase chain reaction assay for deletions on chromosome 20q (del20q), screened peripheral blood granulocytes from 664 patients with myeloproliferative disorders, and identified 19 patients with del20q (2.9%), of which 14 (74%) were also positive for JAK2-V617F. To examine the temporal relationship between the occurrence of del20q and JAK2-V617F, we performed colony assays in methylcellulose, picked individual burst-forming units–erythroid (BFU-E) and colony-forming units–granulocyte (CFU-G) colonies, and genotyped each colony individually for del20q and JAK2-V617F. In 2 of 9 patients, we found that some colonies with del20q carried only wild-type JAK2, whereas other del20q colonies were JAK2-V617F positive, indicating that del20q occurred before the acquisition of JAK2-V617F. However, in colonies from 3 of 9 patients, we observed the opposite order of events. The lack of a strict temporal order of occurrence makes it doubtful that del20q represents a predisposing event for JAK2-V617F. In 2 patients with JAK2-V617F and 1 patient with MPL-W515L, microsatellite analysis revealed that del20q affected chromosomes of different parental origin and/or 9pLOH occurred at least twice. The fact that rare somatic events, such as del20q or 9pLOH, occurred more than once in subclones from the same patients suggests that the myeloproliferative disorder clone carries a predisposition to acquiring such genetic alterations.
Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress–induced cell death
Authors: Mougiakakos Dimitrios , Johansson C. Christian , Kiessling Rolf
Published: December 2008

Although the authors of several studies report elevated numbers of immunosuppressive regulatory T cells (Tregs) in hematologic and solid malignancies, the underlying mechanism is not fully clarified. Cancer is associated with oxidative stress mediated through reactive oxygen species produced by malignant cells, granulocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Oxidative stress is known to have detrimental effects on natural killer (NK) and T cells during chronic inflammatory conditions and cancer. Paradoxically, greater numbers of Tregs can be detected at tumor sites, indicating that Tregs can persist in this environment of increased oxidative stress. We demonstrate that Tregs, especially naive CD45RA+, exhibit reduced sensitivity to oxidative stress–induced cell death and maintain their suppressive function, a phenomenon that may be attributed to their observed high antioxidative capacity. This newly described characteristic could explain their enrichment in malignancies associated with increased levels of oxidative stress.
Differential diagnosis and management of focal ground-glass opacities
Authors: Infante M. , Lutman R. F. , Imparato S. , Di Rocco M. , Ceresoli G. L. , Torri V. , Morenghi E. , Minuti F. , Cavuto S. , Bottoni E. , Inzirillo F. , Cariboni U. , Errico V. , Incarbone M. A. , Ferraroli G. , Brambilla G. , Alloisio M. , Ravasi G.
Published: December 2008

Focal pulmonary ground-glass opacities (GGOs) can be associated with bronchioloalveolar carcinoma. The present retrospective study aimed to test the validity of a multistep approach to discriminate malignant from benign localised (focal) GGOs, identifies useful diagnostic features on computed tomography (CT), and suggests appropriate management guidelines.

A stepwise approach, including oral antibiotics, follow-up high-resolution CT (HRCT) 40–60 days later and CT-guided core biopsy, was used. All cases with localised GGOs detected since 2001 were reviewed. CT features were described according to a structured scheme. In total, 40 patients were evaluated. Of these, 11 patients were diagnosed with benign GGOs, 19 patients had lung cancer and 10 were undetermined.

Nonpolygonal shape, apparent radial growth and clear-cut margins were associated with a malignant histology. The specificity of CT findings was low. Diagnostic accuracy increased after oral antibiotics, follow-up HRCT and percutaneous core biopsy. Overall, 18 patients underwent surgery for lung cancer.

In conclusion, malignant ground-glass opacities have a fairly typical appearance, but some benign lesions closely mimic their malignant counterparts. The stepwise approach adopted in the present study increased the diagnostic specificity and reduced time to definitive diagnosis. Segmentectomy might be the ideal resection volume for such tumours.
Diagnostic value of interleukin-12 p40 in tuberculous pleural effusions
Authors: Valdés L. , San José E. , Álvarez Dobaño J. M. , Golpe A. , Valle J. M. , Penela P. , González Barcala F. J.
Published: December 2008

The diagnosis of tuberculous pleural effusion (TBPE) is frequently problematic. Several markers of TBPE in pleural fluid have been evaluated, with different results.

Pleural effusions from 96 patients were classified on the basis of definitive diagnosis as tuberculous (n = 39), neoplastic (n = 42) or parapneumonic (n = 15). Adenosine deaminase (ADA), ADA isoform ADA-2, interferon (IFN)-γ, CD3+/DR+T-lymphocytes and interleukin (IL)-12 p40 were determined in all 96 effusions. The efficiency of IL-12 p40 for diagnosis of TBPEs was evaluated, in comparison with those of the other parameters, by comparing the areas under their receiver operating characteristics.

With the threshold value of 550 pg·mL−1, IL-12 p40 had a sensitivity of 92.3% (36 out of 39) and specificity of 70.2% (17 false positives). The misclassification rate of IL-12 p40 was significantly greater than those of ADA-2 and ADA. Among TBPEs, ADA correlated significantly with ADA-2, and IFN-γ with ADA and IL-12 p40.

Although tuberculous pleural effusions show values of interleukin-12 p40 that are significantly higher than neoplastic and parapneumonic fluids, this parameter is less efficient than adenosine deaminase, adenosine deaminase isoform 2 and interferon-γ. Its routine determination is, accordingly, not justified.
QuantiFERON-TB Gold and the TST are both useful for latent tuberculosis infection screening in autoimmune diseases
Authors: Bartalesi F. , Vicidomini S. , Goletti D. , Fiorelli C. , Fiori G. , Melchiorre D. , Tortoli E. , Mantella A. , Benucci M. , Girardi E. , Cerinic M. M. , Bartoloni A.
Published: December 2008

Screening for active tuberculosis (TB) and latent TB infection (LTBI) is mandatory prior to the initiation of tumour necrosis factor-α inhibitor therapy. However, no agreement exists on the best strategy for detecting LTBI in this population. The aim of the present study was to analyse the performance of the tuberculin skin test (TST) and QuantiFERON®-TB Gold in-tube (QFT-GIT) on LTBI detection in subjects with immunomediated inflammatory diseases (IMID).

The TST and QFT-GIT were prospectively performed in 398 consecutive IMID subjects, 310 (78%) on immunosuppressive therapy and only 16 (4%) had been bacillus Calmette–Guérin (BCG) vaccinated.

Indeterminate results to QFT-GIT were found in five (1.2%) subjects. Overall, 74 (19%) out of 393 subjects were TST-positive and 52 (13%) were QFT-GIT-positive. Concordance between TST and QFT-GIT results was good (87.7%): 13 were QFT-GIT-positive/TST-negative and 35 QFT-GIT-negative/TST-positive. By multivariate analysis both tests were significantly associated with older age. Only the TST was associated with BCG vaccination and radiological lesions of past TB. Use of immunosuppressive drugs differently modulated QFT-GIT or TST scoring.

Use of the QuantiFERON®-TB Gold in-tube, as a screening tool for latent tuberculosis among immunomediated inflammatory disease subjects, is feasible. Until further data will elucidate discordant tuberculin skin test/QuantiFERON®-TB Gold in-tube results, a strategy of simultaneous tuberculin skin and QuantiFERON®-TB Gold in-tube testing in a low prevalence bacillus Calmette–Guérin vaccinated population, should maximise potentials of latent tuberculosis diagnosis.
Comparison of methods for estimating the nucleotide substitution matrix
Authors: Oscamou Maribeth , McDonald Daniel , Yap Von Bing , Huttley Gavin A , Lladser Manuel E , Knight Rob
Published: December 2008

Background

The nucleotide substitution rate matrix is a key parameter of molecular evolution. Several methods for inferring this parameter have been proposed, with different mathematical bases. These methods include counting sequence differences and taking the log of the resulting probability matrices, methods based on Markov triples, and maximum likelihood methods that infer the substitution probabilities that lead to the most likely model of evolution. However, the speed and accuracy of these methods has not been compared.

Results

Different methods differ in performance by orders of magnitude (ranging from 1 ms to 10 s per matrix), but differences in accuracy of rate matrix reconstruction appear to be relatively small. Encouragingly, relatively simple and fast methods can provide results at least as accurate as far more complex and computationally intensive methods, especially when the sequences to be compared are relatively short.

Conclusion

Based on the conditions tested, we recommend the use of method of Gojobori et al. (1982) for long sequences (> 600 nucleotides), and the method of Goldman et al. (1996) for shorter sequences (< 600 nucleotides). The method of Barry and Hartigan (1987) can provide somewhat more accuracy, measured as the Euclidean distance between the true and inferred matrices, on long sequences (> 2000 nucleotides) at the expense of substantially longer computation time. The availability of methods that are both fast and accurate will allow us to gain a global picture of change in the nucleotide substitution rate matrix on a genomewide scale across the tree of life.
Genomic complexity of the variable region-containing chitin-binding proteins in amphioxus
Authors: Dishaw Larry J , Mueller M Gail , Gwatney Natasha , Cannon John P , Haire Robert N , Litman Ronda T , Amemiya Chris T , Ota Tatsuya , Rowen Lee , Glusman Gustavo , Litman Gary W
Published: December 2008

Background

The variable region-containing chitin-binding proteins (VCBPs) are found in protochordates and consist of two tandem immunoglobulin variable (V)-type domains and a chitin-binding domain. We previously have shown that these polymorphic genes, which primarily are expressed in the gut, exhibit characteristics of immune genes. In this report, we describe VCBP genomic organization and characterize adjacent and intervening genetic features which may influence both their polymorphism and complex transcriptional repertoire.

Results

VCBP genes 1, 2, 4, and 5 are encoded in a single contiguous gene-rich chromosomal region and VCBP3 is encoded in a separate locus. The VCBPs exhibit extensive haplotype variation, including copy number variation (CNV), indel polymorphism and a markedly elevated variation in repeat type and density. In at least one haplotype, inverted repeats occur more frequently than elsewhere in the genome. Multi-animal cDNA screening, as well as transcriptional profilingusing a novel transfection system, suggests that haplotype-specific transcriptional variants may contribute to VCBP genetic diversity.

Conclusion

The availability of the Branchiostoma floridae genome (Joint Genome Institute, Brafl1), along with BAC and PAC screening and sequencing described here, reveal that the relatively limited number of VCBP genes present in the amphioxus genome exhibit exceptionally high haplotype variation. These VCBP haplotypes contribute a diverse pool of allelic variants, which includes gene copy number variation, pseudogenes, and other polymorphisms, while contributing secondary effects on gene transcription as well.
Probing of Actinobacillus pleuropneumoniae ApxIIIA toxin-dependent cytotoxicity towards mammalian peripheral blood mononucleated cells
Authors: Vanden Bergh Philippe GAC , Zecchinon Laurent LM , Fett Thomas , Desmecht Daniel
Published: December 2008

Background

Actinobacillus pleuropneumoniae, the causative bacterial agent of porcine pleuropneumonia, produces Apx toxins which belong to RTX toxin family and are recognized as the major virulence factors. So far, their target receptor(s) has not been identified and the disease cytopathogenesis remains poorly understood. Production of an active Apx toxin and characterization of its toxic activity constitute the premises necessary to the description of its interaction with a potential receptor. From this point of view, we produced an active recombinant ApxIIIA toxin in order to characterize its toxicity on peripheral blood mononucleated cells (PBMCs) isolated from several species.

Findings

Toxin preparation exercises a strong cytotoxic action on porcine PBMCs which is directly related to recombinant ApxIIIA since preincubation with polymyxin B does not modify the cytotoxicity rate while preincubation with a monospecific polyclonal antiserum directed against ApxIIIA does. The cell death process triggered by ApxIIIA is extremely fast, the maximum rate of toxicity being already reached after 20 minutes of incubation. Moreover, ApxIIIA cytotoxicity is species-specific because llama, human, dog, rat and mouse PBMCs are resistant. Interestingly, bovine and caprine PBMCs are slightly sensitive to ApxIIIA toxin too. Finally, ApxIIIA cytotoxicity is cell type-specific as porcine epithelial cells are resistant.

Conclusion

We have produced an active recombinant ApxIIIA toxin and characterized its specific cytotoxicity on porcine PBMCs which will allow us to get new insights on porcine pleuropneumonia pathogenesis in the future.
An artificial intelligence tool to predict fluid requirement in the intensive care unit: a proof-of-concept study
Authors: Celi Leo Anthony , Hinske Christian L , Alterovitz Gil , Szolovits Peter
Published: December 2008

Introduction

The goal of personalised medicine in the intensive care unit (ICU) is to predict which diagnostic tests, monitoring interventions and treatments translate to improved outcomes given the variation between patients. Unfortunately, processes such as gene transcription and drug metabolism are dynamic in the critically ill; that is, information obtained during static non-diseased conditions may have limited applicability. We propose an alternative way of personalising medicine in the ICU on a real-time basis using information derived from the application of artificial intelligence on a high-resolution database. Calculation of maintenance fluid requirement at the height of systemic inflammatory response was selected to investigate the feasibility of this approach.

Methods

The Multi-parameter Intelligent Monitoring for Intensive Care II (MIMIC II) is a database of patients admitted to the Beth Israel Deaconess Medical Center ICU in Boston. Patients who were on vasopressors for more than six hours during the first 24 hours of admission were identified from the database. Demographic and physiological variables that might affect fluid requirement or reflect the intravascular volume during the first 24 hours in the ICU were extracted from the database. The outcome to be predicted is the total amount of fluid given during the second 24 hours in the ICU, including all the fluid boluses administered.

Results

We represented the variables by learning a Bayesian network from the underlying data. Using 10-fold cross-validation repeated 100 times, the accuracy of the model in predicting the outcome is 77.8%. The network generated has a threshold Bayes factor of seven representing the posterior probability of the model given the observed data. This Bayes factor translates into p < 0.05 assuming a Gaussian distribution of the variables.

Conclusions

Based on the model, the probability that a patient would require a certain range of fluid on day two can be predicted. In the presence of a larger database, analysis may be limited to patients with identical clinical presentation, demographic factors, co-morbidities, current physiological data and those who did not develop complications as a result of fluid administration. By better predicting maintenance fluid requirements based on the previous day's physiological variables, one might be able to prevent hypotensive episodes requiring fluid boluses during the course of the following day.
Tumor Cavitation: Impact on Objective Response Evaluation in Trials of Angiogenesis Inhibitors in Non–Small-Cell Lung Cancer
Authors: Crabb Simon J. , Patsios Demetris , Sauerbrei Eric , Ellis Peter M. , Arnold Andrew , Goss Glenwood , Leighl Natasha B. , Shepherd Frances A. , Powers Jean , Seymour Lesley , Laurie Scott A.
Published: December 2008

Purpose

We have observed cavitation of lesions in clinical trials of an angiogenesis inhibitor combined with chemotherapy for non–small-cell lung cancer (NSCLC). We hypothesized that cavitation might alter response assessment in such clinical trials.

Patients and Methods

We performed a retrospective radiologic review of patients with NSCLC enrolled onto three National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trials of platinum-based chemotherapy with or without a small-molecule angiogenesis inhibitor (vascular endothelial growth factor receptor inhibitor [VEGFRI]). Response was assessed both by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and a novel alternate method in which the longest diameter of any cavity was subtracted from the overall longest diameter of that lesion to measure target lesions. Rates of cavitation were documented.

Results

Marked cavitation of pulmonary lesions was seen in 24% of 33 patients treated with VEGFRI combined with platinum-based chemotherapy but in none of 18 patients treated with platinum-based chemotherapy alone. Use of the alternate method for response assessment resulted in an alteration of response assessment, time to best response, duration of response, and time of disease progression in a minority of patients compared with RECIST.

Conclusion

Cavitation of target and nontarget lesions is common in NSCLC patients treated with VEGFRIs and platinum-based chemotherapy. Impact on response and time to event outcomes occurred but seems to be less common. Response assessment might be improved by incorporating cavitation into volume assessment for target lesions, potentially altering outcomes of key efficacy parameters in clinical trials. This should be prospectively assessed in clinical trials of angiogenesis inhibitors.
The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force Report
Authors: Cohn Susan L. , Pearson Andrew D.J. , London Wendy B. , Monclair Tom , Ambros Peter F. , Brodeur Garrett M. , Faldum Andreas , Hero Barbara , Iehara Tomoko , Machin David , Mosseri Veronique , Simon Thorsten , Garaventa Alberto , Castel Victoria , Matthay Katherine K.
Published: December 2008

Purpose

Because current approaches to risk classification and treatment stratification for children with neuroblastoma (NB) vary greatly throughout the world, it is difficult to directly compare risk-based clinical trials. The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification.

Patients and Methods

The statistical and clinical significance of 13 potential prognostic factors were analyzed in a cohort of 8,800 children diagnosed with NB between 1990 and 2002 from North America and Australia (Children's Oncology Group), Europe (International Society of Pediatric Oncology Europe Neuroblastoma Group and German Pediatric Oncology and Hematology Group), and Japan. Survival tree regression analyses using event-free survival (EFS) as the primary end point were performed to test the prognostic significance of the 13 factors.

Results

Stage, age, histologic category, grade of tumor differentiation, the status of the MYCN oncogene, chromosome 11q status, and DNA ploidy were the most highly statistically significant and clinically relevant factors. A new staging system (INRG Staging System) based on clinical criteria and tumor imaging was developed for the INRG Classification System. The optimal age cutoff was determined to be between 15 and 19 months, and 18 months was selected for the classification system. Sixteen pretreatment groups were defined on the basis of clinical criteria and statistically significantly different EFS of the cohort stratified by the INRG criteria. Patients with 5-year EFS more than 85%, more than 75% to ≤ 85%, ≥ 50% to ≤ 75%, or less than 50% were classified as very low risk, low risk, intermediate risk, or high risk, respectively.

Conclusion

By defining homogenous pretreatment patient cohorts, the INRG classification system will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world and the development of international collaborative studies.
Prognostic Significance of Serum S100B Protein in High-Risk Surgically Resected Melanoma Patients Participating in Intergroup Trial ECOG 1694
Authors: Tarhini Ahmad A. , Stuckert Joseph , Lee Sandra , Sander Cindy , Kirkwood John M.
Published: December 2008

Purpose

We evaluated adjuvant trial E1694 to more precisely define the prognostic significance of serum S100B in patients with high-risk resected melanoma.

Patients and Methods

Sera from 670 E1694 patients banked at baseline and three additional time points were tested for S100B protein using chemiluminescence.

Results

S100B testing results showed that the higher the S100B level is, the higher the risk of relapse and death, regardless of the cutoff value. Univariate analysis showed that baseline S100B ≥ 0.15 μg/L is significantly correlated with overall survival (OS; P = .01). Multivariate analysis was performed adjusting for significant prognostic factors (ulceration and lymph node status) and treatment. Baseline S100B was a significant prognostic factor for survival (hazard ratio = 1.39; 95% CI, 1.01 to 1.92; P = .043). S100B values measured at later time points over 1 year were also demonstrated to be significant prognostic factors for relapse-free survival (RFS) and OS. Lower S100B values at baseline and during follow-up were associated with longer survival. A changing S100B from low at baseline to high on follow-up seemed to be associated with the worst RFS and OS.

Conclusion

For patients with high-risk surgically resected melanoma, a high baseline or increasing serum S100B is an independent prognostic marker of risk for mortality that may allow us to refine the application of adjuvant therapy in the future.