bluuebunny/crossref_metadata_2025 huggingface dataset:
Political Possibility, Hypercapitalism, and the “Conservative Reeducation Machine”
Authors: Cannella Gaile S.
Published: July 2011

The education machine constructed by right wing politics and discourses has been of great concern for some time, especially during the Bush administration. However, actions by the Obama administration have further accelerated that reeducation machine by maintaining legislation like NCLB and support for educational corporations. This paper describes how this hypercapitalist conservative machine continues to use forms of signification and resource redistribution as mechanisms of power, masks cultural and intellectual diversity, co-opts identities, and corporatizes all aspects of education (including the ways we construct and understand learning) to interpret them as competition, privatization, and profiteering. Politicians from both (or all) political parties may be so attached to the tentacles of hypercaptialism that radical thought and actions are necessary to save and construct education that is socially just, equitable, and democratic.
Underlying Agreements Between Quantitative and Qualitative Research
Authors: Newman Isadore , Hitchcock John H.
Published: July 2011

A review of the methodological literature describing mixed-methods and quantitative and qualitative research paradigms suggest that though many have rejected the so-called paradigm wars there remains much focus on what is different about each research tradition. This has borne out in practice where professional organizations often have subgroups dedicated to the study of one tradition or another. Indeed, Human Resources Development Review has issued calls for manuscripts that explore this topic. This article examines the idea that there can be times when it is best to think of research as a monolithic paradigm rather than a distinct set of subparadigms. The reason for this is there are a number of common research scenarios where it is best to apply perspectives that might typically be characterized as qualitative as well as ones that are considered to be qualitative in orientation (e.g., using contextual information to make judgments about practical significance). There are other scenarios where the underlying goal of a procedure from, say the quantitative paradigm is similar to that from the qualitative realm (e.g., exploratory factor analyses and thematic analyses). There are of course real differences among the paradigms, but overemphasis on division might obfuscate how to conduct rigorous research. The article closes by encouraging readers to let their research questions dictate methodological approach, in the context of the purpose, rather than building questions around techniques that tend to align with different subparadigms.
A Unique Case of a Type II Endoleak After EVAR Caused by Patent Inferior Mesenteric and Accessory Renal Arteries
Authors: Franz Randall W. , Nguyen Thanh V.
Published: July 2011

Type II endoleaks have been viewed as the Achilles’ heel of endovascular repair of abdominal aortic aneurysms. This report describes a unique etiology to this common challenge and our approach to endovascular repair.
Use of Theoretical Frameworks as a Pragmatic Guide for Mixed Methods Studies
Authors: Evans Bronwynne C. , Coon David W. , Ume Ebere
Published: July 2011

There is a growing acceptance of the utility of mixed methods in health sciences but there is no widely accepted set of ideas with regard to use of a conceptual or theoretical framework to guide inquiry. Few mixed methods health science articles report the use of such a framework. Lack of available conceptual maps provided by theoretical frameworks, necessary intricacy of design, and the qualitative “black box” tradition all contribute to a dearth of methodological guidance in such studies. This article uses a funded National Institutes of Health study as an example to explain the utility of a theoretical framework in conceptualizing a study, making design decisions such as sampling and recruitment, collecting and analyzing data, and data interpretation.
The Influence of Guest Perceptions of Service Fairness on Lodging Loyalty in China
Authors: Kwortnik Robert J. , Han Xiaoyun
Published: July 2011

This research is motivated by an important but largely unexamined question: how do guest perceptions of service fairness influence loyalty in a lodging context? To address this question, this study presents a conceptual model of service fairness and loyalty and tests that model using data collected from 601 customers of six hotels in China. Results support a multidimensional view of service fairness that comprises three dimensions. Two of those dimensions, distributive justice (fair outcomes) and interactional justice (fair treatment by staff), have larger effects on customer loyalty than does the third dimension, procedural justice (fair processes and procedures). A key implication is that hotel managers should train their employees to understand that guests’ evaluation of a service (and subsequent trust and loyalty) depends not only on specific service outcomes, but also on how guests feel they have been treated by employees.
Stock Performance of Firms Acquiring Listed and Unlisted Lodging Assets
Authors: Ma Qingzhong , Zhang Wei , Chowdhury Namir
Published: July 2011

Examining a large sample of acquisitions involving both listed (publicly traded) and unlisted (privately held firms or subsidiaries) lodging assets, this article reports that acquirers earn significant positive abnormal returns in both cases. However, these positive abnormal returns are primarily realized in deals involving unlisted targets. This remains true even after controlling for many deal and firm characteristics. Within the subset of acquisitions of unlisted targets, acquirer abnormal returns are significantly higher when relative size is greater, when at least some stock is tendered for the acquisition, and when the acquirer has not been active in acquisition in prior years.
Using Service Blueprinting to Analyze Restaurant Service Efficiency
Authors: Hummel Emily , Murphy Kevin S.
Published: July 2011

A time and motion study of 152 transactions at six restaurants operated by a full-service casual chain in Florida illustrates the use of service blueprinting as a method for analyzing service process efficiency. At management’s request, the researchers conducted the time and motion study to observe the extent to which individual servers followed company-mandated policies and procedures, and how well those procedures worked. Although this is a case study only and the observations cannot be generalized, the researchers noted a mixed picture with regard to policy observance and service efficiency. The restaurant chain uses a wine presentation process as a suggestive selling technique on greeting guests, but in this study the wine presentation resulted in a smaller than anticipated number of glasses sold. Moreover, unlike most suggestive selling, the wine presentation was a separate process that did not mesh with the meal order and delivery. In addition, rather than follow policy and drop checks when they check back on entrées, servers were waiting until the end of the meal to present the check, often when guests requested it. This policy omission may have added time to the table occupancy and reduced table turns. One procedure that was regularly observed—and worked successfully—was the “food ready” policy, in which any server would carry food to any table when that food was ready (instead of having the food stand until the “official” server could get it). These examples demonstrate how a comparison of actual performance to the service blueprint can show areas of inefficiency, both in terms of failure to follow policy and in terms of policies that are not as effective as expected.
Acute Exertional Rhabdomyolysis and Triceps Compartment Syndrome During a High School Football Camp
Authors: Oh John Y. , Laidler Matthew , Fiala Steven C. , Hedberg Katrina
Published: July 2011

Background: Acute exertional rhabdomyolysis has been infrequently reported among adolescents. In August 2010, several high school football players from one team developed rhabdomyolysis and triceps compartment syndrome following an upper arm exercise held in a non-air-conditioned wrestling room.

Purpose: To confirm the diagnoses, characterize the spectrum of illnesses, and determine the factors contributing to rhabdomyolysis and triceps compartment syndromes.

Study Design: Descriptive epidemiology study.

Methods: The authors reviewed hospital medical records and interviewed players, coaches, school administrators, and hospital staff, using a standardized questionnaire that assessed symptoms, exposures, and activities.

Results: Among 43 players, 22 (51%) experienced rhabdomyolysis (peak creatine kinase range, 2434-42 000 U/L): 22 patients had upper arm myalgia; 12 were hospitalized; 3 experienced triceps compartment syndrome; none experienced renal failure. Illnesses started 1 to 3 days after the triceps exercise. Forty players (93%) completed questionnaires. Among 19 players receiving at least 1 vote from a teammate as 1 of the 3 hardest working players, 13 (68%) experienced rhabdomyolysis versus 7 (33%) of 21 not considered hardest working (relative risk, 2.1; 95% confidence interval, 1.04-4.0). Of 40 players, 10 (25%) reported creatine supplement use, which was not associated with rhabdomyolysis. No player acknowledged use of alcohol, illicit drugs, or performance-enhancing drugs; results of performance-enhancing drug tests on the 4 players tested were negative. Environmental investigation did not identify additional factors contributing to illness.

Conclusions: The upper arm exercise, possibly exacerbated by heat, led to rhabdomyolysis and compartment syndrome. Greater awareness of specific exercise hazards and prevention strategies can minimize risk for clinically significant muscle injury.
An 8-Stage Model for Evaluating the Tennis Serve
Authors: Kovacs Mark , Ellenbecker Todd
Published: July 2011

Background: The tennis serve is a complex stroke characterized by a series of segmental rotations involving the entire kinetic chain. Many overhead athletes use a basic 6-stage throwing model; however, the tennis serve does provide some differences.

Evidence Acquisition: To support the present 8-stage descriptive model, data were gathered from PubMed and SPORTDiscus databases using keywords tennis and serve for publications between 1980 and 2010.

Results: An 8-stage model of analysis for the tennis serve that includes 3 distinct phases—preparation, acceleration, and follow-through—provides a more tennis-specific analysis than that previously presented in the clinical tennis literature. When a serve is evaluated, the total body perspective is just as important as the individual segments alone.

Conclusion: The 8-stage model provides a more in-depth analysis that should be utilized in all tennis players to help better understand areas of weakness, potential areas of injury, as well as components that can be improved for greater performance.
Structural variants of IFNα preferentially promote antiviral functions
Authors: Vázquez Nancy , Schmeisser Hana , Dolan Michael A. , Bekisz Joseph , Zoon Kathryn C. , Wahl Sharon M.
Published: July 2011

IFNα, a cytokine with multiple functions in innate and adaptive immunity and a potent inhibitor of HIV, exerts antiviral activity, in part, by enhancing apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 (APOBEC3) family members. Although IFNα therapy is associated with reduced viral burden, this cytokine also mediates immune dysfunction and toxicities. Through detailed mapping of IFNα receptor binding sites, we generated IFNα hybrids and mutants and determined that structural changes in the C-helix alter the ability of IFN to limit retroviral activity. Selective IFNα constructs differentially block HIV replication and their directional magnitude of inhibition correlates with APOBEC3 levels. Importantly, certain mutants exhibited reduced toxicity as reflected by induced indoleamine 2,3-dioxygenase (IDO), suggesting discreet and shared intracellular signaling pathways. Defining IFN structure and function relative to APOBEC and other antiviral genes may enable design of novel IFN-related molecules preserving beneficial antiviral roles while minimizing negative effects.
NK cell education after allogeneic transplantation: dissociation between recovery of cytokine-producing and cytotoxic functions
Authors: Foley Bree , Cooley Sarah , Verneris Michael R. , Curtsinger Julie , Luo Xianghua , Waller Edmund K. , Weisdorf Daniel J. , Miller Jeffrey S.
Published: July 2011

Natural killer (NK) cells mediate GVL effects after allogeneic hematopoietic cell transplantation (allo-HCT) by the production of inflammatory cytokines and by direct target lysis. The acquisition of both functions was presumed to be developmentally linked, but this linkage remained unstudied after allo-HCT. We tested the cytokine production and degranulation of reconstituting NK cells after adult unrelated donor or umbilical cord blood grafting. Recipients of T cell–depleted transplants, receiving no immune suppression, showed diminished NK cell degranulation. In contrast, degranulation was normal or increased after T-cell replete transplants given with immune suppression. Strikingly, target cell-induced IFNγ production was markedly diminished in all transplant settings, especially with T cell–depleted or naive T cell–containing umbilical cord blood grafts, suggesting a role for T cells in NK education. Although degranulation was similar in the KIR+ and KIR− populations that coexpressed NKG2A, target cell-induced IFNγ production was limited to the subset of NK cells expressing KIR inhibited by self-ligands. Thus, cytokine production and cytotoxic function do not consistently coexist in NK cells reconstituting after allo-HCT. Exposure to IL-15 rapidly increased target-inducible IFNγ production, indicative of IL-15's potential as a therapeutic tool to enhance NK cell function to protect against infection and relapse after allo-HCT.
IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques
Authors: Lugli Enrico , Mueller Yvonne M. , Lewis Mark G. , Villinger Francois , Katsikis Peter D. , Roederer Mario
Published: July 2011

Human immunodeficiency virus (HIV) infection is characterized by a progressive loss of memory CD4+ T cells in multiple tissues, especially at mucosal surfaces where most of these cells reside. Although antiretroviral therapy (ART) suppresses viral replication and promotes the recovery of peripheral CD4+ T cells, HIV-infected patients fail to fully reconstitute the CD4+ T-cell pool at mucosal sites. IL-15 has been shown to preferentially expand memory-phenotype T cells and promote their migration to nonlymphoid tissues. Here we examined IL-15 treatment in combination with highly active ART in chronically SIV-infected rhesus macaques and found that IL-15 delayed viral suppression and failed to enhance ART-induced total and antigen-specific CD4+ T-cell reconstitution at mucosal and lymphoid sites. IL-15 was able to induce the transient proliferation of SIV-specific, CMV-specific, and total memory CD8+ T cells, but not of SIV-specific or total CD4+ T cells. Moreover, upon treatment interruption, macaques receiving combined IL-15+ART lost CD4+ T cells faster than those receiving ART alone. These results suggest that the combination of IL-15 with highly active ART is not more efficient than ART alone in promoting CD4+ T-cell recovery in HIV-infected individuals and may accelerate CD4+ T-cell loss after treatment interruption.
Pathogenesis and treatment of xanthomatosis associated with monoclonal gammopathy
Authors: Szalat Raphael , Arnulf Bertrand , Karlin Lionel , Rybojad Michel , Asli Bouchra , Malphettes Marion , Galicier Lionel , Vignon-Pennamen Marie-Dominique , Harel Stéphanie , Cordoliani Florence , Fuzibet Jean Gabriel , Oksenhendler Eric , Clauvel Jean-Pierre , Brouet Jean-Claude , Fermand Jean-Paul
Published: July 2011

Xanthomas are a common manifestation of lipid metabolism disorders. They include hyperlipemic xanthoma, normolipemic xanthoma, and a related condition, necrobiotic xanthogranuloma (NXG). All 3 forms can be associated with monoclonal immunoglobulin (MIg). In an attempt to improve diagnosis, understanding, and treatment of this association, we retrospectively analyzed a personal series of 24 patients (2 hyperlipemic xanthoma, 11 normolipemic xanthoma, and 11 NXG) and 230 well-documented reports from the literature. With the exception of the nodules and plaques featured in NXG, the clinical presentation of xanthomatous lesions usually resembled that seen in common hyperlipidemic forms and could not be used to suspect MIg-associated xanthomas. Extracutaneous sites were not rare. The MIg was an IgG in 80% of cases. Myeloma was diagnosed in 35%. Hypocomplementemia with low C4 fraction was present in 80% of studied patients. Low C1 inhibitor serum levels were found in 53%. Cryoglobulinemia was detected in 27%. These abnormalities suggest immune complex formation because of interactions between the MIg and lipoproteins and argue in favor of a causal link between MIg and xanthomas. Monoclonal gammopathy therapy could thus be an option. Indeed, among the patients who received chemotherapy, hematologic remission was accompanied by improvement in xanthoma lesions in several cases.
Reproductive capacity in iron overloaded women with thalassemia major
Authors: Singer Sylvia T. , Vichinsky Elliott P. , Gildengorin Ginny , van Disseldorp Jereon , Rosen Mitchell , Cedars Marcelle I.
Published: July 2011

The pathophysiology of iron-induced compromised fertility in women with thalassemia major (TM) was evaluated in 26 adult TM females. Low gonadotropin secretion resulted in reduced ovarian antral follicle count and ovarian volume, but levels of anti-müllerian hormone (AMH), a sensitive marker for ovarian reserve independent of gonadotropin effect, were mostly normal. AMH correlated with non–transferrin-bound iron (NTBI), suggesting a role of labile iron in the pathogenesis of decreased reproductive capacity, possibly occurring in parallel to cardiac iron toxicity, as cardiac iron was associated with the presence of amenorrhea and with NTBI levels. AMH emerges as an important biomarker for assessment of reproductive capacity in TM, demonstrating that fertility is preserved in the majority of those younger than 30 to 35 years. AMH can be useful in future studies aiming at improved chelation for fertility preservation, whereas NTBI and labile plasma iron may be valuable for monitoring iron effect on the reproductive system.
The long-term consequences of hybridization between the two Daphnia species, D. galeata and D. dentifera, in mature habitats
Authors: Ishida Seiji , Takahashi Akiko , Matsushima Noe , Yokoyama Jun , Makino Wataru , Urabe Jotaro , Kawata Masakado
Published: July 2011

Background

Ecological specializations such as antipredator defense can reinforce morphological and distributional divergence within hybridizing species. Two hybridizing species ofDaphnia(D. galeataandD. dentifera) are distributed in both Japan and North America; however, these populations have a longer history in Japan than in North America due to the differing impact of the last glaciation on these two regions. We tested the hypothesis that this longer coexistence in Japan would lead to extensive genetic admixture in nuclear and mitochondrial DNA whilst the distinct morphological traits and distributional patterns would be maintained.

Results

The high level of correspondence among morphological traits, distribution, and mitochondrial and nuclear DNA types for the specimens withD. dentiferamtDNA indicated that the species distinction has been maintained. However, a discordance between mtDNA and nuclear ITS-1 types was observed for most specimens that hadD. galeatamtDNA, consistent with the pattern seen between the two species in North America. This observation suggests nuclear introgression fromD. dentiferaintoD. galeatawithout mitochondrial introgression.

Conclusions

The separation of morphological traits and distribution ranges of the two hybridizing species in Japan, as well as in North America, has been maintained, despite large differences in climatic and geographical histories of these two regions. Variations in environmental factors, such as predation pressure, might affect maintenance of the distribution, although the further studies are needed to confirm this.
Integration of Genome-Wide Computation DRE Search, AhR ChIP-chip and Gene Expression Analyses of TCDD-Elicited Responses in the Mouse Liver
Authors: Dere Edward , Lo Raymond , Celius Trine , Matthews Jason , Zacharewski Timothy R
Published: July 2011

Background

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor (TF) that mediates responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Integration of TCDD-induced genome-wide AhR enrichment, differential gene expression and computational dioxin response element (DRE) analyses further elucidate the hepatic AhR regulatory network.

Results

Global ChIP-chip and gene expression analyses were performed on hepatic tissue from immature ovariectomized mice orally gavaged with 30 μg/kg TCDD. ChIP-chip analysis identified 14,446 and 974 AhR enriched regions (1% false discovery rate) at 2 and 24 hrs, respectively. Enrichment density was greatest in the proximal promoter, and more specifically, within ± 1.5 kb of a transcriptional start site (TSS). AhR enrichment also occurred distal to a TSS (e.g. intergenic DNA and 3' UTR), extending the potential gene expression regulatory roles of the AhR. Although TF binding site analyses identified over-represented DRE sequences within enriched regions, approximately 50% of all AhR enriched regions lacked a DRE core (5'-GCGTG-3'). Microarray analysis identified 1,896 number of TCDD-responsive genes (|fold change| ≥ 1.5, P1(t) > 0.999). Integrating this gene expression data with our ChIP-chip and DRE analyses only identified 625 differentially expressed genes that involved an AhR interaction at a DRE. Functional annotation analysis of differentially regulated genes associated with AhR enrichment identified overrepresented processes related to fatty acid and lipid metabolism and transport, and xenobiotic metabolism, which are consistent with TCDD-elicited steatosis in the mouse liver.

Conclusions

Details of the AhR regulatory network have been expanded to include AhR-DNA interactions within intragenic and intergenic genomic regions. Moreover, the AhR can interact with DNA independent of a DRE core suggesting there are alternative mechanisms of AhR-mediated gene regulation.
To compare the efficacy of two kinds of Zhizhu pills in the treatment of functional dyspepsia of spleen-deficiency and qi-stagnation syndrome:a randomized group sequential comparative trial
Authors: Wu Hongli , Jing Zhiwei , Tang Xudong , Wang Xinyue , Zhang Shengsheng , Yu Yanan , Wang Zhong , Cao Hongxin , Huang Luqi , Yu Youhua , Wang Yongyan
Published: July 2011

Background

In Traditional Chinese Medicine (TCM) theory, functional dyspepsia (FD) can be divided into different syndromes according to different clinical symptoms and signs, and the most common one is spleen-deficiency and qi-stagnation syndrome that can be treated by Chinese traditional patent medicine ---- two kinds of Zhizhu pills, between which the primary difference in ingredients is that one contains immature orange fruit of Citrus aurantium L.(IFCA) and the other contains that of Citrus sinensis Osbeck (IFCS). The trial's objective was to compare the efficacy of two kinds of Zhizhu pills on symptom changes in patients with FD of spleen-deficiency and qi-stagnation syndrome.

Methods

A randomized, group sequential, double-blinded, multicenter trial was conducted in patients with FD of spleen-deficiency and qi-stagnation syndrome at 3 hospitals in Beijing between June 2003 and May 2005. Participants were randomly allocated into two groups (IFCA group and IFCS group) in a 1:1 ratio, and respectively took one of the two kinds of Zhizhu pills orally, 6 g each time, 3 times a day, for 4 weeks. Statistical analysis was performed with use of a group sequential method, the triangular test (TT).

Results

A total of 163 patients were randomized, and 3 patients were excluded from analysis because of early dropouts, leaving 160 patients (IFCA group: n = 82; IFCS group: n = 78) for statistical analysis. Three interim analyses were done after 62, 116, and 160 patients had completed their 4-week treatment, respectively. At the third interim analysis, the sample path crossed the upper boundary and the trial was stopped, the cure-markedly effective rates were 45% for IFCS group and 67% for IFCA group, respectively, the one-sided p-value was 0.0036, the median unbiased estimate of the odds ratio (OR) for the benefit of IFCA relative to IFCS was 2.91 with 95%CI: 1.40 to 6.06.

No adverse events were observed in the two groups.

Conclusions

Zhizhu pills containing IFCA was superior to Zhizhu pills containing IFCS in the treatment of FD of spleen-deficiency and qi-stagnation syndrome. The application of group sequential analysis in clinical trials of TCM may offer some financial and ethical benefits.

Trial Registration

Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC-00000485
Asthma control in patients receiving inhaled corticosteroid and long-acting beta2-agonist fixed combinations. A real-life study comparing dry powder inhalers and a pressurized metered dose inhaler extrafine formulation
Authors: Müller Veronika , Gálffy Gabriella , Eszes Noemi , Losonczy György , Bizzi Andrea , Nicolini Gabriele , Chrystyn Henry , Tamási Lilla
Published: July 2011

Background

Although patients have more problems using metered dose inhalers, clinical comparisons suggest they provide similar control to dry powder inhalers. Using real-life situations this study was designed to evaluate asthma control in outpatients with moderate to severe persistent asthma and to compare efficacy of fixed combinations of inhaled corticosteroids (ICS) and long acting beta-agonists (LABA).

Methods

This real-life study had a cross-sectional design. Patients using fixed combinations of ICS and LABA had their asthma control and spirometry assessed during regular visits.

Results

111 patients were analyzed: 53 (47.7%) received maintenance therapy of extrafine beclomethasone-formoterol (BDP/F) pressurized metered dose inhaler (pMDI), 25 (22.5%) fluticasone-salmeterol (FP/S) dry powder inhaler (DPI), and 33 (29.7%) budesonide-formoterol (BUD/F) DPI. Severity of asthma at time of diagnosis, assessed by the treating physician, was comparable among groups. Asthma control was achieved by 45.9% of patients; 38.7% were partially controlled and 15.3% were uncontrolled. In the extrafine BDF/F group, asthma control total score, daytime symptom score and rescue medication use score were significantly better than those using fixed DPI combinations (5.8 ± 6.2 vs. 8.5 ± 6.8; 1.4 ± 1.8 vs. 2.3 ± 2.1; 1.8 ± 2.2 vs. 2.6 ± 2.2; p = 0.0160; p = 0.012 and p = 0.025, respectively) and the mean daily ICS dose were significantly lower.

Conclusions

pMDI extrafine BDP/F combination demonstrated better asthma control compared to DPIs formulated with larger particles. This could be due to the improved lung deposition of the dose or less reliance on the optimal inhalation technique or both.
Complement component C5a Promotes Expression of IL-22 and IL-17 from Human T cells and its Implication in Age-related Macular Degeneration
Authors: Liu Baoying , Wei Lai , Meyerle Catherine , Tuo Jingsheng , Sen H Nida , Li Zhiyu , Chakrabarty Sagarika , Agron Elvira , Chan Chi-Chao , Klein Michael L , Chew Emily , Ferris Frederick , Nussenblatt Robert B
Published: July 2011

Background

Age related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly populations worldwide. Inflammation, among many factors, has been suggested to play an important role in AMD pathogenesis. Recent studies have demonstrated a strong genetic association between AMD and complement factor H (CFH), the down-regulatory factor of complement activation. Elevated levels of complement activating molecules including complement component 5a (C5a) have been found in the serum of AMD patients. Our aim is to study whether C5a can impact human T cells and its implication in AMD.

Methods

Human peripheral blood mononuclear cells (PBMCs) were isolated from the blood of exudative form of AMD patients using a Ficoll gradient centrifugation protocol. Intracellular staining and enzyme-linked immunosorbent assays were used to measure protein expression. Apoptotic cells were detected by staining of cells with the annexin-V and TUNEL technology and analyzed by a FACS Caliber flow cytometer. SNP genotyping was analyzed by TaqMan genotyping assay using the Real-time PCR system 7500.

Results

We show that C5a promotes interleukin (IL)-22 and IL-17 expression by human CD4+ T cells. This effect is dependent on B7, IL-1β and IL-6 expression from monocytes. We have also found that C5a could protect human CD4+ cells from undergoing apoptosis. Importantly, consistent with a role of C5a in promoting IL-22 and IL-17 expression, significant elevation in IL-22 and IL-17 levels was found in AMD patients as compared to non-AMD controls.

Conclusions

Our results support the notion that C5a may be one of the factors contributing to the elevated serum IL-22 and IL-17 levels in AMD patients. The possible involvement of IL-22 and IL-17 in the inflammation that contributes to AMD may herald a new approach to treat AMD.
Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells
Authors: Metz Stefan W , Geertsema Corinne , Martina Byron E , Andrade Paulina , Heldens Jacco G , van Oers Monique M , Goldbach Rob W , Vlak Just M , Pijlman Gorben P
Published: July 2011

Background

Chikungunya virus (CHIKV) is a mosquito-borne, arthrogenic Alphavirus that causes large epidemics in Africa, South-East Asia and India. Recently, CHIKV has been transmitted to humans in Southern Europe by invading and now established Asian tiger mosquitoes. To study the processing of envelope proteins E1 and E2 and to develop a CHIKV subunit vaccine, C-terminally his-tagged E1 and E2 envelope glycoproteins were produced at high levels in insect cells with baculovirus vectors using their native signal peptides located in CHIKV 6K and E3, respectively.

Results

Expression in the presence of either tunicamycin or furin inhibitor showed that a substantial portion of recombinant intracellular E1 and precursor E3E2 was glycosylated, but that a smaller fraction of E3E2 was processed by furin into mature E3 and E2. Deletion of the C-terminal transmembrane domains of E1 and E2 enabled secretion of furin-cleaved, fully processed E1 and E2 subunits, which could then be efficiently purified from cell culture fluid via metal affinity chromatography. Confocal laser scanning microscopy on living baculovirus-infected Sf 21 cells revealed that full-length E1 and E2 translocated to the plasma membrane, suggesting similar posttranslational processing of E1 and E2, as in a natural CHIKV infection. Baculovirus-directed expression of E1 displayed fusogenic activity as concluded from syncytia formation. CHIKV-E2 was able to induce neutralizing antibodies in rabbits.

Conclusions

Chikungunya virus glycoproteins could be functionally expressed at high levels in insect cells and are properly glycosylated and cleaved by furin. The ability of purified, secreted CHIKV-E2 to induce neutralizing antibodies in rabbits underscores the potential use of E2 in a subunit vaccine to prevent CHIKV infections.
An Integrated Mathematical Model of Thrombin-, Histamine-and VEGF-Mediated Signalling in Endothelial Permeability
Authors: Wei XN , Han BC , Zhang JX , Liu XH , Tan CY , Jiang YY , Low BC , Tidor B , Chen YZ
Published: July 2011

Background

Endothelial permeability is involved in injury, inflammation, diabetes and cancer. It is partly regulated by the thrombin-, histamine-, and VEGF-mediated myosin-light-chain (MLC) activation pathways. While these pathways have been investigated, questions such as temporal effects and the dynamics of multi-mediator regulation remain to be fully studied. Mathematical modeling of these pathways facilitates such studies. Based on the published ordinary differential equation models of the pathway components, we developed an integrated model of thrombin-, histamine-, and VEGF-mediated MLC activation pathways.

Results

Our model was validated against experimental data for calcium release and thrombin-, histamine-, and VEGF-mediated MLC activation. The simulated effects of PAR-1, Rho GTPase, ROCK, VEGF and VEGFR2 over-expression on MLC activation, and the collective modulation by thrombin and histamine are consistent with experimental findings. Our model was used to predict enhanced MLC activation by CPI-17 over-expression and by synergistic action of thrombin and VEGF at low mediator levels. These may have impact in endothelial permeability and metastasis in cancer patients with blood coagulation.

Conclusion

Our model was validated against a number of experimental findings and the observed synergistic effects of low concentrations of thrombin and histamine in mediating the activation of MLC. It can be used to predict the effects of altered pathway components, collective actions of multiple mediators and the potential impact to various diseases. Similar to the published models of other pathways, our model can potentially be used to identify important disease genes through sensitivity analysis of signalling components.
Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis
Authors: Vélez de Mendizábal Nieves , Carneiro Jorge , Solé Ricard V , Goñi Joaquín , Bragard Jean , Martinez-Forero Ivan , Martinez-Pasamar Sara , Sepulcre Jorge , Torrealdea Javier , Bagnato Francesca , Garcia-Ojalvo Jordi , Villoslada Pablo
Published: July 2011

Background

The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS). Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e.g. failure in central tolerance, activation by pathogens) that are able to trigger the immune system.

Results

The model represents five concepts: central tolerance (T-cell generation by the thymus), T-cell activation, T-cell memory, cross-regulation (negative feedback) between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system.

Conclusion

The relapsing dynamic in MS derives from the emergent properties of the immune system operating in a pathological state, a fact that has implications for predicting disease course and developing new therapies for MS.
Multi-locus sequence typing of Ehrlichia ruminantium strains from geographically diverse origins and collected in Amblyomma variegatum from Uganda
Authors: Nakao Ryo , Magona Joseph W , Zhou Lijia , Jongejan Frans , Sugimoto Chihiro
Published: July 2011

Background

The rickettsial bacterium Ehrlichia ruminantium is the causative agent of heartwater in ruminants. A better understanding of the population genetics of its different strains is, however, needed for the development of novel diagnostic tools, therapeutics and prevention strategies. Specifically, the development of effective vaccination policies relies on the proper genotyping and characterisation of field isolates. Although multi-locus sequence typing (MLST) has been recently developed, only strains from geographically restricted collections have been analysed so far. The expansion of the MLST database to include global strains with different geographic origins is therefore essential. In this study, we used a panel of reference strains from geographically diverse origins and field samples of E. ruminantium detected from its vector, Amblyomma variegatum, in heartwater-endemic areas in Uganda.

Results

A total of 31 novel alleles (six, four, six, three, two, five, three, and two for gltA, groEL, lepA, lipA, lipB, secY, sodB, and sucA loci, respectively) and 19 novel sequence types (STs) were identified. Both neighbour-joining and minimum spanning tree analyses indicated a high degree of genetic heterogeneity among these strains. No association was observed between genotypes and geographic origins, except for four STs from West African countries. When we performed six different tests for recombination (GeneConv, Bootscan, MaxChi, Chimaera, SiScan, and 3Seq) on concatenated sequences, four possible recombination events were identified in six different STs. All the recombination breakpoints were located near gene borders, indicating the occurrence of intergenic recombination. All four STs that localized to a distinct group in clustering analysis showed evidence of identical recombination events, suggesting that recombination may play a significant role in the diversification of E. ruminantium.

Conclusions

The compilation of MLST data set across the African continent will be particularly valuable for the understanding of the existing genetic diversity of field isolates in African countries. Comprehensive information on the degree of cross-protection between strains and further understanding of possible relationships between genotypes and phenotypes such as vaccine efficacy are expected to lead to the development of region-specific vaccination strategies.
C-reactive protein, an early marker of community-acquired sepsis resolution: a multi-center prospective observational study
Authors: Póvoa Pedro , Teixeira-Pinto Armando M , Carneiro António H ,   the Portuguese Community-Acquired Sepsis Study Group (SACiUCI)
Published: July 2011

Introduction

C-reactive protein (CRP) has been shown to be a valuable marker in the diagnosis of infection and in monitoring its response to antibiotics. Our objective was to evaluate serial CRP measurements after prescription of antibiotics to describe the clinical course of Community-Acquired Sepsis admitted to intensive care units (ICU).

Methods

During a 12-month period a multi-center, prospective, observational study was conducted, segregating adults with Community-Acquired Sepsis. Patients were followed-up during the first five ICU days, day of ICU discharge or death and hospital outcome. CRP-ratio was calculated in relation to Day 1 CRP concentration. Patients were classified according to the pattern of CRP-ratio response to antibiotics: fast response if Day 5 CRP-ratio was < 0.4, slow response if Day 5 CRP-ratio was between 0.4 and 0.8, and no response if Day 5 CRP-ratio was > 0.8. Comparison between survivors and non-survivors was performed.

Results

A total of 891 patients (age 60 ± 17 yrs, hospital mortality 38%) were studied. There were no significant differences between the CRP of survivors and non-survivors until Day 2 of antibiotic therapy. On the following three days, CRP of survivors was significantly lower (P < 0.001). After adjusting for the Simplified Acute Physiology Score II and severity of sepsis, the CRP course was significantly associated with mortality (ORCRP-ratio = 1.03, confidence interval 95%= (1.02, 1.04), P < 0.001). The hospital mortality of patients with fast response, slow response and no response patterns was 23%, 30% and 41%, respectively (P = 0.001). No responders had a significant increase on the odds of death (OR = 2.5, CI95% = (1.6, 4.0), P < 0.001) when compared with fast responders.

Conclusions

Daily CRP measurements after antibiotic prescription were useful as early as Day 3 in identification of Community-Acquired Sepsis patients with poor outcome. The rate of CRP decline during the first five ICU days was markedly associated with prognosis. The identification of the pattern of CRP-ratio response was useful in the recognition of the individual clinical course.
Natural Language Processing and the Oncologic History: Is There a Match?
Authors: Warner Jeremy L. , Anick Peter , Hong Pengyu , Xue Nianwen
Published: July 2011

The widespread adoption of electronic health records within the oncology community is creating rich databases that contain details of the cancer care continuum. Large portions of this information are locked up in free text, but several efforts are underway to address this.
Integrated Information Systems for Electronic Chemotherapy Medication Administration
Authors: Levy Mia A. , Giuse Dario A. , Eck Carol , Holder Gwen , Lippard Giles , Cartwright Julia , Rudge Nancy K.
Published: July 2011

Paper-based approaches to medication administration have several disadvantages and do not provide any decision support for patient safety checks. Electronic medication administration may provide additional safety checks and enable consistent documentation structure.
Effect of an Electronic Health Record on the Culture of an Outpatient Medical Oncology Practice in a Four-Hospital Integrated Health Care System: 5-Year Experience
Authors: Brockstein Bruce , Hensing Thomas , Carro George W. , Obel Jennifer , Khandekar Janardan , Kaminer Lynne , Van De Wege Christine , de Wilton Marsh Robert
Published: July 2011

Five years after implementation of a full paperless electronic health record within a four-hospital care system, the system's oncology practice is experiencing significant improvements in safety, efficiency, and research productivity in both inpatient and outpatient settings.
Electronic Chemotherapy Order Entry: A Major Cancer Center's Implementation
Authors: Sklarin Nancy T. , Granovsky Svetlana , O'Reilly Eileen M. , Zelenetz Andrew D.
Published: July 2011

Implementation of computerized provider order entry for complex chemotherapy regimens supported Memorial Sloan-Kettering Cancer Center's strategic plan to successfully establish a distributive, networked health care delivery system.
Creating a Process to Standardize Regimen Order Sets Within an Electronic Health Record
Authors: Busby Leslie T. , Sheth Sheetal , Garey Jody , Ginsburg Aimee , Flynn Thomas , Willen Michael A. , Kruger Scott , Neubauer Marcus A. , Kolodziej Michael , Chang David , Palmer Eric Scott , McGuinness Margaret , Egerton Nancy J. , Merriman Jan , Herbeck Eileen B. , Fetter Alison , Frisk Linda , Sitarik Mark , Anderson Roger , Beveridge Roy
Published: July 2011

Electronic health records systems, such as iKnowMed, can provide standardized order sets for a large oncology network, but the regimens must be evaluated routinely using standardized procedures to ensure accuracy.
Patient-Physician E-Mail Communication: The Kaiser Permanente Experience
Authors: Baer David
Published: July 2011

The American Medical Association and American Medical Informatics Association guidelines provide excellent advice to those seeking to incorporate physician-patient e-mail communication into their practices.
Oncologist-Hospital Alignment Models Built to Compensate Oncologists Fairly
Authors: Barkley Ronald R. , Guidi Teri U.
Published: July 2011

What can oncologists entering into alignment relationships with hospitals and academic medical centers expect to be paid for their professional contribution?
Computerized Provider Order Entry in Pediatric Oncology: Design, Implementation, and Outcomes
Authors: Chen Allen R. , Lehmann Christoph U.
Published: July 2011

Implementation of computerized provider order entry required extensive customization but improved patient safety in a highly complex pediatric oncology environment.
A New Look at Informed Consent for Cancer Clinical Trials
Authors: Baer Allison R. , Good Marge , Schapira Lidia
Published: July 2011

Informed consent is fundamental to the conduct of clinical trials. Prospective participants need to be adequately informed and given the opportunity to ask questions and consult with relatives or friends without feeling pressured or rushed.
Harmonin (Ush1c) is required in zebrafish Müller glial cells for photoreceptor synaptic development and function
Authors: Phillips Jennifer B. , Blanco-Sanchez Bernardo , Lentz Jennifer J. , Tallafuss Alexandra , Khanobdee Kornnika , Sampath Srirangan , Jacobs Zachary G. , Han Philip F. , Mishra Monalisa , Titus Tom A. , Williams David S. , Keats Bronya J. , Washbourne Philip , Westerfield Monte
Published: July 2011

Usher syndrome is the most prevalent cause of hereditary deaf-blindness, characterized by congenital sensorineural hearing impairment and progressive photoreceptor degeneration beginning in childhood or adolescence. Diagnosis and management of this disease are complex, and the molecular changes underlying sensory cell impairment remain poorly understood. Here we characterize two zebrafish models for a severe form of Usher syndrome, Usher syndrome type 1C (USH1C): one model is a mutant with a newly identified ush1c nonsense mutation, and the other is a morpholino knockdown of ush1c. Both have defects in hearing, balance and visual function from the first week of life. Histological analyses reveal specific defects in sensory cell structure that are consistent with these behavioral phenotypes and could implicate Müller glia in the retinal pathology of Usher syndrome. This study shows that visual defects associated with loss of ush1c function in zebrafish can be detected from the onset of vision, and thus could be applicable to early diagnosis for USH1C patients.
Simulation of digital scan conversion for ultrasound systems using a digital signal processor
Authors: Bera Deep , Agarwal Leeladhar , Banerjee Swapna
Published: July 2011

B-mode ultrasound systems use digital scan conversion (DSC) to display data in a Cartesian coordinate system acquired in a polar coordinate format. Image quality depends on the quality of the interpolation algorithm applied to the unsampled pixels to avoid artefacts. In this paper, a warped distance-based adaptive bilinear interpolation technique with selective sampling is proposed and has been successfully simulated using a Texas Instruments (TI) digital signal processor series TMS320C64x+ cycle accurate simulator. The algorithm enhances both the detail in the different regions as well as preserving the smooth regions within the image, yielding better image quality with less computational complexity. Optimized implementation of the algorithm supports software pipelining. Additionally, the approach speeds up the computation by utilizing the ability of very long instruction word processor to perform multiple operations in parallel. The experimental results show that the DSC is capable of supporting 83 frames per second without sacrificing the image quality for a raw input image of size, 512 × 256 scanned with an angle of 58° and output video graphics array (640 × 480) display.