bluuebunny/crossref_metadata_2025 huggingface dataset:
Fairness Perceptions and Organizational Misbehavior: An Empirical Study
Authors: De Schrijver Annelies , Delbeke Karlien , Maesschalck Jeroen , Pleysier Stefaan
Published: October 2010

Employees evaluate the fairness or justice of their workplace: Does one get what one deserves at work? Organizational scholars consider perceived workplace fairness to be a relevant factor in predicting and explaining organizational misbehavior. For instance, Treviño and Weaver found in their study that the more employees perceive that their organization is just, the less they perceive their colleagues to be engaged in behavior that harms the organization. This hypothesis was retested with an alternative measure of organizational misbehavior in 19 Flemish governmental organizations, and confirmation was found. Moreover, the effect holds when controlling for integrity policy, leadership, tenure, and gender.
Marketing Myths and Marketing Realities: A Commentary on the Consumer as Voter, Judge and Jury
Authors: Shaw Eric H.
Published: October 2010

Offering a counterpoint to ‘‘The Consumer as Voter, Judge and Jury,’’ this commentary compares the ‘‘modern origins’’ of the ‘‘marketing myths’’ in the article with an alternative view; contrasts the ‘‘new agora’’ analogy with the old Agora; and assesses the apocalyptic vision in the article with an analogous ‘‘triptych.’’ Further, this commentary evaluates the article’s ‘‘political legitimacy’’ argument for marketing practice versus the economic efficiency argument, and it considers the long-term survival and growth of socialist versus market economies. Finally, the commentary questions whether the analogies between ‘‘citizen and consumer voting’’ and between ‘‘citizen and consumer sovereignty’’ are marketing myths or realities.
Prophylaxis of hemicrania continua: Three cases effectively treated with acemethacin
Authors: Nicpoń Krzysztof J , Nicpoń Krzysztof W , Jaroszuk-Nicpoń Joanna
Published: October 2010

Hemicrania continua is a daily headache disorder that is characterized by unilateral, constant pain with exacerbations of intensity accompanied by autonomic symptoms. Response to indomethacin is the diagnostic criterion for hemicrania continua, but efficacy of indomethacin in therapy is restricted because of gastrointestinal adverse events. Therefore, many patients are disqualified from treatment with indomethacin, creating a need to search for alternative therapy. In comparison with indomethacin, acemethacin seems to have a better therapeutic profile. It is associated with fewer gastrointestinal adverse events while having a good therapeutic effect. We present three patients effectively treated with acemethacin without adverse events of the gastrointestinal tract.
Brainstem changes in 5-HT1A receptor availability during migraine attack
Authors: Demarquay G , Lothe A , Royet JP , Costes N , Mick G , Mauguière F , Ryvlin P
Published: October 2010

Background: Among serotonin receptors, 5-HT1A receptors are implicated in the regulation of central serotoninergic tone and could be involved in the abnormal brain 5-HT turnover suspected in migraineurs. The aim of this study was to investigate 5-HT1A receptors’ availability during migraine attacks.

Methods: Ten patients suffering from odor-triggered migraine attacks and 10 control subjects were investigated using positron emission tomography (PET) and [18F]MPPF PET tracer, a selective 5-HT1A antagonist. All subjects underwent calibrated olfactory stimulations prior to the PET study.

Results: Four patients developed a migraine attack during the PET study. In these patients, statistical parametrical mapping and region of interest analyses showed an increased [18F]MPPF binding potential (BPND) in the pontine raphe when compared to headache-free migraineurs and control subjects. This ictal change was confirmed at the individual level in each of the four affected patients. In comparison with the headache-free migraineurs, patients with a migraine attack also showed significantly increased [18F]MPPF BPND in the left orbitofrontal cortex, precentral gyrus and temporal pole. No significant change in [18F]MPPF BPND was observed between headache-free migraineurs and controls.

Conclusions: Our results emphasize the role of 5HT1A receptors in the pontine raphe nuclei during the early stage of migraine attacks.
Factors Affecting Healing Rates after Arthroscopic Double-Row Rotator Cuff Repair
Authors: Tashjian Robert Z. , Hollins Anthony M. , Kim Hyun-Min , Teefey Sharlene A. , Middleton William D. , Steger-May Karen , Galatz Leesa M. , Yamaguchi Ken
Published: October 2010

Background

Double-row arthroscopic rotator cuff repairs were developed to improve initial biomechanical strength of repairs to improve healing rates. Despite biomechanical improvements, failure of healing remains a clinical problem.

Purpose

To evaluate the anatomical results after double-row arthroscopic rotator cuff repair with ultrasound to determine postoperative repair integrity and the effect of various factors on tendon healing.

Study Design

Case series; Level of evidence, 4.

Methods

Forty-eight patients (49 shoulders) who had a complete arthroscopic rotator cuff repair (double-row technique) were evaluated with ultrasound at a minimum of 6 months after surgery. Outcome was evaluated at a minimum of 1-year follow-up with standardized history and physical examination, visual analog scale for pain, active forward elevation, and preoperative and postoperative shoulder scores according to the system of the American Shoulder and Elbow Surgeons and the Simple Shoulder Test. Quantitative strength was measured postoperatively.

Results

Ultrasound and physical examinations were performed at a minimum of 6 months after surgery (mean, 16 months; range, 6 to 36 months) and outcome questionnaire evaluations at a minimum of 12 months after surgery (mean, 29 months; range, 12 to 55 months). Of 49 repairs, 25 (51%) were healed. Healing rates were 67% in single-tendon tears (16 of 24 shoulders) and 36% in multitendon tears (9 of 25 shoulders). Older age and longer duration of follow-up were correlated with poorer tendon healing (P < .03). Visual analog scale for pain, active forward elevation, American Shoulder and Elbow Surgeons scores, and Simple Shoulder Test scores all had significant improvement from baseline after repair (P < .0001).

Conclusion

Increased age and longer duration of follow-up were associated with lower healing rates after double-row rotator cuff repair. The biological limitation at the repair site, as reflected by the effects of age on healing, appears to be the most important factor influencing tendon healing, even after maximizing repair biomechanical strength with a double-row construct.
Change and Continuity
Authors: Bjelde Kristine E. , Sanders Gregory F.
Published: October 2010

This qualitative study examined lifestyles of older adults who migrate south in the winter. Interviews were conducted with 25 older adults (aged 60+) from the upper Midwest. Analyses revealed the following themes, including (a) snowbirds were flexible and adaptable to change, (b) there was continuity in personality, activity, and lifestyle, (c) friendships were established and maintained, (d) lifestyles were diverse, (e) health and safety considerations affected lifestyle, (f) internal and external forces shaped the snowbird experience, and (g) seasonal migration was developmental. Seasonal migration had a major impact in promoting quality of life and providing added meaning to the lives of these older adults. This study lent support for the concept of seasonal migration as an alternative to permanent migration (e.g., Smith & House, 2006), as well as McHugh and Mings’ (1996) circular life-course trajectory and place attachment. The snowbird experience can be explained as involving developmental change and continuity, family resiliency and connectedness, and successful aging.
DMS cyclone separation processes for optimization of plastic wastes recycling and their implications
Authors: Gent Malcolm Richard , Menendez Mario , Toraño Javier , Torno Susana
Published: October 2010

It is demonstrated that substantial reductions in plastics presently disposed of in landfills can be achieved by cyclone density media separation (DMS). In comparison with the size fraction of plastics presently processed by industrial density separations (generally 6.4 to 9.5 mm), cyclone DMS methods are demonstrated to effectively process a substantially greater range of particle sizes (from 0.5 up to 120 mm). The purities of plastic products and recoveries obtained with a single stage separation using a cylindrical cyclone are shown to attain virtually 100% purity and recoveries >99% for high-density fractions and >98% purity and recoveries were obtained for low-density products. Four alternative schemas of multi-stage separations are presented and analyzed as proposed methods to obtain total low- and high-density plastics fraction recoveries while maintaining near 100% purities. The results of preliminary tests of two of these show that the potential for processing product purities and recoveries >99.98% of both density fractions are indicated. A preliminary economic comparison of capital costs of DMS systems suggests cyclone DMS methods to be comparable with other DMS processes even if the high volume capacity for recycling operations of these is not optimized.
Long term monitoring of leachate flux into drainage pipes of MSW landfills
Authors: Münnich Kai , Bauer Jan , Fricke Klaus
Published: October 2010

The measurement of leachate quality and quantity is an essential part of the monitoring of landfills in the different phases during their lifespan. These measurements allow the evaluation of the decomposition processes in the landfill and the efficiency of technical installations for the reduction of the leachate generation. Normally the measurements are made at the outlet of larger sections of the landfill or at the overall landfill. An identification of smaller parts with different biological or hydraulic behaviour within the landfill section is not possible in that case. In the framework of a long-term research project concerning the monitoring of landfills, different devices for small-scale identification of the leachate discharge were developed at the Technical University of Braunschweig. The device allows a measurement of the leachate discharge inside a single drainage pipe having a length up to 375 m. The measurements showed the influence of changes in operation. It was found that the discharge in the pipes and the efficiency of the drainage system was strongly influenced by deformations and torsion of the high-density polyethylene pipes and unequal settlements of the subsoil. The discharge of leachate in the drainage system was, as expected, very non-uniform and in parts the leachate was not flowing inside the pipes, but rather in the surrounding gravel layer. Furthermore, large differences in leachate quality may occur, whereas the differences in discharge volume are small. With the developed system it is possible to control the efficiency and the functioning of top cover systems for landfills.
Assessing Social Participation of Students With Special Needs in Inclusive Education: Validation of the Social Participation Questionnaire
Authors: Koster Marloes , Minnaert Alexander E. M. G. , Nakken Han , Jan Pijl Sip , van Houten Els J.
Published: October 2010

This study addresses the convergent validity of a new teacher questionnaire to assess the social participation of students with special needs in regular primary schools. The Social Participation Questionnaire (SPQ) consists of four subscales representing four key themes of social participation: friendships/relationships, contacts/interactions, student’s social self-perception, and acceptance by classmates. The study took place in Grades 1 to 3 of regular Dutch primary schools that had at least one student with an official special-needs statement. A confirmatory factor analysis using the LISREL program provided evidence for the SPQ’s convergent validity. The outcomes support the model of social participation distinguishing four key themes. The fit indexes suggest that our model is theoretically viable for Grades 1 and 2 but only partly viable for Grade 3.
Revisiting the golden era of MacLehose and the dynamics of social reforms
Authors: Yep Ray , Lui Tai-Lok
Published: October 2010

The so-called “MacLehose era” has been fondly remembered as a period marking the turning point in colonial rule in Hong Kong and its socioeconomic development in the postwar decades. This article, however, argues that it was London’s initiatives summarized in the document Hong Kong Planning Paper that accounted for the acceleration of social reforms in the 1970s. Contrary to popular perception, MacLehose, who was beholden to local constraints, appeared to be a reluctant reformer. His inclination to defend his vision of the colony’s interests brought him into heated exchanges and debates with British officials who were driven by different political calculations and strategic concerns back home. The altercations uncovered in this article reveal that the colony’s perimeter for action is certainly defined by the position of the sovereign; yet, the outcome of the process was hardly preordained. Beneath the facade of subservience and accommodation, colonial administrators had stubbornly defended their vision of local interests and tried to implement the reforms at their own pace. They appeared not to be swayed by the asymmetry of power in constitutional terms.
Understanding the autonomy of Hong Kong from historical and comparative perspectives
Authors: Yep Ray
Published: October 2010

The exercise of autonomy is a product of the political process of mutual learning by the center and the periphery. Propriety of action and response from both sides is not judged simply on the basis of formal legal permissibility, but is also deciphered with reference to experience in previous encounters. Earlier exchanges and responses to interactions create institutional memory, protocols for action, and limits to legitimate expectations. For both the Hong Kong Special Administrative Region and the central people’s government, the new framework, through mutual adjustment and adaptation, is still in the process of being made. Their parallel experience in handling the central and local relationship can serve as a good basis for their exchanges. The articles included in this issue provide comparisons in temporal and spatial terms that are crucial for understanding the autonomy of Hong Kong after 1997. These contributions do not simply reconfirm the disposition of local players to defend and assert their interests vis-a-vis the center; the discussion here also identifies factors shaping the manifestation of autonomy in the case of Hong Kong. Trust, reciprocity, agenda of the sovereign power, and resolution of conflict appear to be significant in shaping the outcome of centre—periphery interaction.
Managing and Educating Outside: A Cree Hunter’s Perspective on Management Education
Authors: Jolly Freddy , Whiteman Gail , Atkinson Miriam , Radu Ioana
Published: October 2010

Educational approaches addressing environmental sustainability are of growing interest to management educators. The James Bay Cree in Canada offer a novel and ecologically embedded approach to management education as an inspiring template for integrating a deep sense-of-place within management education. The authors describe the Cree approach as “managing outside”; literally managing out of doors on (and with) the land. They develop their ideas collaboratively with FJ, a Cree tallyman (a senior hunter and leader of his family’s hunting territory). FJ challenges modern managers and students interested in sustainability to learn how to manage and educate outside, to relocate and relate their management education to specific local places by working collaboratively with Indigenous Peoples in a participatory manner.
Review. Sulfur-containing Volatile Compounds in Seafood: Occurrence, Odorant Properties and Mechanisms of Formation
Authors: Varlet V. , Fernandez X.
Published: October 2010

An inventory of the most part of sulfur-containing volatile compounds (SCVCs) present in seafood was carried out. These molecules constitute key compounds to understand and improve seafood quality. According to their nature, concentration and environmental parameters (temperature), they can move the overall seafood odor from desirable to rotten. Sulfury odors can also indicate problems in sanitary quality. Thus, it is essential to monitor the generation of these compounds to better control the organoleptic and sanitary quality of seafood. SCVC were divided in two categories: aliphatic compounds and cyclic compounds. Among cyclic SCVC, several families of compounds can be distinguished as thiophenes, thiazoles and their respective derivatives. The main pathways of formation of SCVC in seafood are investigated in order to better understand their presence in seafood aroma. Microbial mediated enzymatic reactions are mainly implied in the generation of aliphatic SCVC whereas Maillard reactions are involved in the generation of cyclic SCVC. A small part of SCVC could also derive from the environment by direct bioaccumulation of S-containing molecules or precursors. Then, the occurrence of SCVC in seafood is discussed according to the extraction methods, analysis methods — sometimes olfactometric methods and the species — the state and the average biochemical composition of the seafood matrix in which they were recovered. Finally, among the identified SCVC, the odorant properties of odor-active volatile compounds were investigated. Aromatic notes and odorant thresholds for odorant SCVC of seafood aroma are listed. Both pathways of formation and lists of SCVC linked to their odorant properties constitute important indicators to optimise seafood quality from an organoleptic and sanitary point of view.
Grain Hardness: A Major Determinant of Wheat Quality
Authors: Pasha I. , Anjum F.M. , Morris C.F.
Published: October 2010

Wheat quality, a complex term, depends upon intentional use for unambiguous products. The foremost determinants of wheat quality are endosperm texture (grain hardness), protein content and gluten strength. Endosperm texture in wheat is the single most important and defining quality characteristic, as it facilitates wheat classification and affects milling, baking and end-use quality. Various techniques used for grain hardness measurement are classified into diverse groups according to grinding, crushing and abrasion. The most extensively used methods for texture measurement are PSI, NIR hardness, SKCS, pearling index, SDS-PAGE and PCR markers. Friabilin is a 15 kDa endosperm specific protein associated with starch granules of wheat grain and is unswervingly related to grain softness. Chemically, it is a concoction of different polypeptides, primarily puroindolines; Pin a and Pin b. Hardness (Ha) locus of chromosome 5DS makes the distinction between soft and hard classes of wheat. Some additional modifying genes are also present which contribute to the disparity within wheat classes. Numerous allelic mutations in Pin have been reported and their relation to end product quality has been established. This treatise elaborates the consequence of grain hardness in wheat eminence.
Urban Air Pollution Targets the Dorsal Vagal Complex and Dark Chocolate Offers Neuroprotection
Authors: Villarreal-Calderon Rafael , Torres-Jardón Ricardo , Palacios-Moreno Juan , Osnaya Norma , Pérez-Guillé Beatriz , Maronpot Robert R. , Reed William , Zhu Hongtu , Calderón-Garcidueñas Lilian
Published: October 2010

Mexico City (MC) residents exposed to fine particulate matter and endotoxin exhibit inflammation of the olfactory bulb, substantia nigra, and vagus nerve. The goal of this study was to model these endpoints in mice and examine the neuroprotective effects of chocolate. Mice exposed to MC air received no treatment or oral dark chocolate and were compared to clean-air mice either untreated or treated intraperitoneally with endotoxin. Cyclooxygenase-2 (COX-2), interleukin 1 beta (IL-1β), and CD14 messenger RNA (mRNA) were quantified after 4, 8, and 16 months of exposure in target brain regions. After 16 months of exposure, the dorsal vagal complex (DVC) exhibited significant inflammation in endotoxin-treated and MC mice (COX-2 and IL-1β P < .001). Mexico City mice had olfactory bulb upregulation of CD14 ( P = .002) and significant DVC imbalance in genes for antioxidant defenses, apoptosis, and neurodegeneration. These findings demonstrate sustained DVC inflammation in mice exposed to MC air, which is mitigated by chocolate administration.
Blunt Trauma of the Anterior Tibial Artery in Professional Footballers
Authors: Shalhoub Joseph , English Bryan , Byard Matt , Franklin Ian J.
Published: October 2010

Three cases of blunt trauma to the anterior tibial artery in professional footballers are described. Each case was managed conservatively, allowing the players to promptly return to competitive fixtures. We hope the outcomes of the cases described might be helpful for teams facing the challenge of managing similar injuries.
Politics without Citizens? Public Opinion, Television News, the President, and Real-World Factors in Chile, 2000-2005
Authors: Valenzuela Sebastián , Arriagada Arturo
Published: October 2010

This study tests the generalizability of agenda-setting theory in less developed democracies by analyzing data on public opinion, television news coverage, presidential policy, and real-world indicators from Chile between 2000 and 2005. After tracking attention to five different issues—crime, unemployment, health, poverty, and education—we estimate both average and issue-specific agenda-setting effects using time-series, cross-sectional ordinary least squares (OLS) regressions. The results show that there are multidirectional influences between the public, television news, and the president. Both the public and the president appeared responsive to prior news coverage, and while news coverage was not influenced by public attention, it was affected by presidential rhetoric. While these processes differed from one issue to another, overall there was a top-down pattern of agenda adoption: Policy preferences are “negotiated” between the president and the news media, with no noticeable input from the public. From a comparative perspective, the evidence shows that television news in Chile are considerably powerful and that citizens’ priorities are basically ignored by the elites, although their maneuvering is still constrained by objective conditions.
Endothelial LSP1 is involved in endothelial dome formation, minimizing vascular permeability changes during neutrophil transmigration in vivo
Authors: Petri Björn , Kaur Jaswinder , Long Elizabeth M. , Li Hang , Parsons Sean A. , Butz Stefan , Phillipson Mia , Vestweber Dietmar , Patel Kamala D. , Robbins Stephen M. , Kubes Paul
Published: October 2010

The endothelium actively participates in neutrophil migration out of the vasculature via dynamic, cytoskeleton-dependent rearrangements leading to the formation of transmigratory cups in vitro, and to domes that completely surround the leukocyte in vivo. Leukocyte-specific protein 1 (LSP1), an F-actin–binding protein recently shown to be in the endothelium, is critical for effective transmigration, although the mechanism has remained elusive. Herein we show that endothelial LSP1 is expressed in the nucleus and cytosol of resting endothelial cells and associates with the cytoskeleton upon endothelial activation. Two-photon microscopy revealed that endothelial LSP1 was crucial for the formation of endothelial domes in vivo in response to neutrophil chemokine keratinocyte-derived chemokine (KC) as well as in response to endogenously produced chemokines stimulated by cytokines (tumor necrosis factor α [TNFα] or interleukin-1β [IL-1β]). Endothelial domes were significantly reduced in Lsp1−/− compared with wild-type (WT) mice. Lsp1−/− animals not only showed impaired neutrophil emigration after KC and TNFα stimulation, but also had disproportionate increases in vascular permeability. We demonstrate that endothelial LSP1 is recruited to the cytoskeleton in inflammation and plays an important role in forming endothelial domes thereby regulating neutrophil transendothelial migration. The permeability data may underscore the physiologic relevance of domes and the role for LSP1 in endothelial barrier integrity.
Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma
Authors: Rosenblatt Jacalyn , Vasir Baldev , Uhl Lynne , Blotta Simona , MacNamara Claire , Somaiya Poorvi , Wu Zekui , Joyce Robin , Levine James D. , Dombagoda Dilani , Yuan Yan Emily , Francoeur Karen , Fitzgerald Donna , Richardson Paul , Weller Edie , Anderson Kenneth , Kufe Donald , Munshi Nikhil , Avigan David
Published: October 2010

We have developed a tumor vaccine in which patient-derived myeloma cells are chemically fused with autologous dendritic cells (DCs) such that a broad spectrum of myeloma-associated antigens are presented in the context of DC-mediated costimulation. We have completed a phase 1 study in which patients with multiple myeloma underwent serial vaccination with the DC/multiple myeloma fusions in conjunction with granulocyte-macrophage colony-stimulating factor. DCs were generated from adherent mononuclear cells cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-α and fused with myeloma cells obtained from marrow aspirates. Vaccine generation was successful in 17 of 18 patients. Successive cohorts were treated with 1 × 106, 2 × 106, and 4 × 106 fusion cells, respectively, with 10 patients treated at the highest dose level. Vaccination was well tolerated, without evidence of dose-limiting toxicity. Vaccination resulted in the expansion of circulating CD4 and CD8 lymphocytes reactive with autologous myeloma cells in 11 of 15 evaluable patients. Humoral responses were documented by SEREX (Serologic Analysis of Recombinant cDNA Expression Libraries) analysis. A majority of patients with advanced disease demonstrated disease stabilization, with 3 patients showing ongoing stable disease at 12, 25, and 41 months, respectively. Vaccination with DC/multiple myeloma fusions was feasible and well tolerated and resulted in antitumor immune responses and disease stabilization in a majority of patients.
Ewing sarcoma gene Ews regulates hematopoietic stem cell senescence
Authors: Cho Joonseok , Shen Hongmei , Yu Hui , Li Hongjie , Cheng Tao , Lee Sean Bong , Lee Byeong Chel
Published: October 2010

The longevity of organisms is maintained by stem cells. If an organism loses the ability to maintain a balance between quiescence and differentiation in the stem/progenitor cell compartment due to aging and/or stress, this may result in death or age-associated diseases, including cancer. Ewing sarcoma is the most lethal bone tumor in young patients and arises from primitive stem cells. Here, we demonstrated that endogenous Ewing sarcoma gene (Ews) is indispensable for stem cell quiescence, and that the ablation of Ews promotes the early onset of senescence in hematopoietic stem progenitor cells. The phenotypic and functional changes in Ews-deficient stem cells were accompanied by an increase in senescence-associated β-galactosidase staining and a marked induction of p16INK4a compared with wild-type counterparts. With its relevance to cancer and possibly aging, EWS is likely to play a significant role in maintaining the functional capacity of stem cells and may provide further insight into the complexity of Ewing sarcoma in the context of stem cells.
Active Rac1 improves pathologic VEGF neovessel architecture and reduces vascular leak: mechanistic similarities with angiopoietin-1
Authors: Hoang Mien V. , Nagy Janice A. , Senger Donald R.
Published: October 2010

Architecturally defective, leaky blood vessels typify pathologic angiogenesis induced by vascular endothelial growth factor-A (VEGF-A). Such neovascular defects aggravate disease pathology and seriously compromise the therapeutic utility of VEGF. Endothelial cell (EC) transduction with active L61Rac1 strongly improved VEGF-driven angiogenesis in vivo as measured by increased neovascular density, enhanced lumen formation, and reduced vessel leakiness. Conversely, transduction with dominant-negative N17Rac1 strongly inhibited neovascularization. In vitro, active L61Rac1 promoted organization of cortical actin filaments and vascular cords and improved EC-EC junctions, indicating that improved cytoskeletal dynamics are important to the mechanism by which active L61Rac1 rectifies VEGF-driven angiogenesis. SEW2871, a sphingosine 1-phosphate receptor-1 agonist that activates Rac1 in ECs, improved cord formation and EC-EC junctions in vitro similarly to active L61Rac. Moreover, SEW2871 administration in vivo markedly improved VEGF neovessel architecture and reduced neovascular leak. Angiopoietin-1, a cytokine that “normalizes” VEGF neovessels in vivo, activated Rac1 and improved cord formation and EC-EC junctions in vitro comparably to active L61Rac1, and a specific Rac1 inhibitor blocked these effects. These studies distinguish augmentation of Rac1 activity as a means to rectify the pathologic angioarchitecture and dysfunctionality of VEGF neovessels, and they identify a rational pharmacologic strategy for improving VEGF angiogenesis.
Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma
Authors: Rapoport Aaron P. , Aqui Nicole A. , Stadtmauer Edward A. , Vogl Dan T. , Fang Hong-Bin , Cai Ling , Janofsky Stephen , Chew Anne , Storek Jan , Akpek Gorgun , Badros Ashraf , Yanovich Saul , Tan Ming T. , Veloso Elizabeth , Pasetti Marcela F. , Cross Alan , Philip Sunita , Murphy Heather , Bhagat Rita , Zheng Zhaohui , Milliron Todd , Cotte Julio , Cannon Andrea , Levine Bruce L. , Vonderheide Robert H. , June Carl H.
Published: October 2010

In a phase 1/2 two-arm trial, 54 patients with myeloma received autografts followed by ex vivo anti-CD3/anti-CD28 costimulated autologous T cells at day 2 after transplantation. Study patients positive for human leukocyte antigen A2 (arm A, n = 28) also received pneumococcal conjugate vaccine immunizations before and after transplantation and a multipeptide tumor antigen vaccine derived from the human telomerase reverse transcriptase and the antiapoptotic protein survivin. Patients negative for human leukocyte antigen A2 (arm B, n = 26) received the pneumococcal conjugate vaccine only. Patients exhibited robust T-cell recoveries by day 14 with supraphysiologic T-cell counts accompanied by a sustained reduction in regulatory T cells. The median event-free survival (EFS) for all patients is 20 months (95% confidence interval, 14.6-24.7 months); the projected 3-year overall survival is 83%. A subset of patients in arm A (36%) developed immune responses to the tumor antigen vaccine by tetramer assays, but this cohort did not exhibit better EFS. Higher posttransplantation CD4+ T-cell counts and a lower percentage of FOXP3+ T cells were associated with improved EFS. Patients exhibited accelerated polyclonal immunoglobulin recovery compared with patients without T-cell transfers. Adoptive transfer of tumor antigen vaccine-primed and costimulated T cells leads to augmented and accelerated cellular and humoral immune reconstitution, including antitumor immunity, after autologous stem cell transplantation for myeloma. This study was registered at www.clinicaltrials.gov as NCT00499577.
Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity?
Authors: Falini Brunangelo , Martelli Maria Paola , Bolli Niccolò , Sportoletti Paolo , Liso Arcangelo , Tiacci Enrico , Haferlach Torsten
Published: October 2010

After the discovery of NPM1-mutated acute myeloid leukemia (AML) in 2005 and its subsequent inclusion as a provisional entity in the 2008 World Health Organization classification of myeloid neoplasms, several controversial issues remained to be clarified. It was unclear whether the NPM1 mutation was a primary genetic lesion and whether additional chromosomal aberrations and multilineage dysplasia had any impact on the biologic and prognostic features of NPM1-mutated AML. Moreover, it was uncertain how to classify AML patients who were double-mutated for NPM1 and CEBPA. Recent studies have shown that: (1) the NPM1 mutant perturbs hemopoiesis in experimental models; (2) leukemic stem cells from NPM1-mutated AML patients carry the mutation; and (3) the NPM1 mutation is usually mutually exclusive of biallelic CEPBA mutations. Moreover, the biologic and clinical features of NPM1-mutated AML do not seem to be significantly influenced by concomitant chromosomal aberrations or multilineage dysplasia. Altogether, these pieces of evidence point to NPM1-mutated AML as a founder genetic event that defines a distinct leukemia entity accounting for approximately one-third of all AML.
Increased epithelial permeability in pulmonary fibrosis in relation to disease progression
Authors: Goh N.S.L. , Desai S.R. , Anagnostopoulos C. , Hansell D.M. , Hoyles R.K. , Sato H. , Denton C.P. , Black C.M. , du Bois R.M. , Wells A.U.
Published: October 2010

Epithelial injury contributes to pathogenesis in idiopathic pulmonary fibrosis (IPF) but its role in the interstitial lung disease (ILD) of systemic sclerosis (SSc) is uncertain. We quantified the prognostic significance of inhaled technetium-99m (99mTc)-labelled diethylene triamine pentacetate (DTPA) pulmonary clearance, a marker of the extent of epithelial injury, in both diseases.

Baseline99mTc-DTPA pulmonary clearance was evaluated retrospectively in patients with SSc-ILD (n = 168) and IPF (n = 97) against mortality and disease progression.

In SSc-ILD, the rapidity of total clearance (hazard ratio (HR) 1.02, 95% CI 1.01–1.03; p = 0.001) and the presence of abnormally rapid clearance (HR 2.10; 95% CI 1.25–3.53; p = 0.005) predicted a shorter time to forced vital capcity (FVC) decline, independent of disease severity. These associations were robust in both mild and severe disease. By contrast, in IPF, delayed clearance of the slow component, an expected consequence of honeycomb change, was an independent predictor of a shorter time to FVC decline (HR 1.01, 95% CI 1.00–1.02; p<0.01).

Epithelial injury should be incorporated in pathogenetic models in SSc-ILD. By contrast, outcome is not linked to the overall extent of epithelial injury in IPF, apart from abnormalities ascribable to honeycombing, suggesting that core pathogenetic events may be more spatially focal in that disease.
Exposure to combustion of solid fuel and tuberculosis: a matched case–control study
Authors: Gninafon M. , Ade G. , Aït-Khaled N. , Enarson D.A. , Chiang C-Y.
Published: October 2010

The present study was conducted in Benin to ascertain the association between exposure to combustion of solid fuel (coal and biomass) and tuberculosis.

Cases were consecutive, sputum smear-positive tuberculosis patients never previously treated for tuberculosis for as long as 1 month. Two controls were selected from the neighbourhood of each case, matched by age and sex by a predefined procedure.

A total of 200 new smear-positive cases and 400 neighbourhood controls were enrolled. In univariate analysis, using solid fuel for cooking (OR 1.7, 95% CI 1.1–2.8), ever smoking (OR 5.5, 95% CI 3.1–9.8), male sex (OR 10.5, 95% CI 1.6–71.1), daily use of alcoholic beverages (OR 2.3, 95% CI 1.2–4.2) and having a family member with tuberculosis in the previous 5 yrs (OR 30.5, 95% CI 10.8–85.8) were all significantly associated with tuberculosis cases. When all significant variables were entered into a multivariate conditional logistic regression model, the association between using solid fuel for cooking and tuberculosis cases was no longer statistically significant (adjusted OR 1.4, 95% CI 0.7–2.7).

In conclusion, the association between exposure to combustion of solid fuel and tuberculosis was relatively weak and not statistically significant.
Interferon-γ release assays for the diagnosis of latentMycobacterium tuberculosisinfection: a systematic review and meta-analysis
Authors: Diel R. , Goletti D. , Ferrara G. , Bothamley G. , Cirillo D. , Kampmann B. , Lange C. , Losi M. , Markova R. , Migliori G.B. , Nienhaus A. , Ruhwald M. , Wagner D. , Zellweger J.P. , Huitric E. , Sandgren A. , Manissero D.
Published: October 2010

We conducted a systematic review and meta-analysis to compare the accuracy of the QuantiFERON-TB® Gold In-Tube (QFT-G-IT) and the T-SPOT®.TBassays with the tuberculin skin test (TST) for the diagnosis of latentMycobacterium tuberculosisinfection (LTBI).

The Medline, Embase and Cochrane databases were explored for relevant articles in November 2009. Specificities, and negative (NPV) and positive (PPV) predictive values of interferon-γ release assays (IGRAs) and the TST, and the exposure gradient influences on test results among bacille Calmette–Guérin (BCG) vaccinees were evaluated.

Specificity of IGRAs varied 98–100%. In immunocompetent adults, NPV for progression to tuberculosis within 2 yrs were 97.8% for T-SPOT®.TBand 99.8% for QFT-G-IT. When test performance of an immunodiagnostic test was not restricted to prior positivity of another test, progression rates to tuberculosis among IGRA-positive individuals followed for 19–24 months varied 8–15%, exceeding those reported for the TST (2–3%). In multivariate analyses, the odd ratios for TST positivity following BCG vaccination varied 3–25, whereas IGRA results remained uninfluenced and IGRA positivity was clearly associated with exposure to contagious tuberculosis cases.

IGRAs may have a relative advantage over the TST in detecting LTBI and allow the exclusion ofM. tuberculosisinfection with higher reliability.
Influence of hay and animal feed exposure on respiratory status: a longitudinal study
Authors: Thaon I. , Thiebaut A. , Jochault L. , Lefebvre A. , Laplante J.J. , Dalphin J.C.
Published: October 2010

Our aim was to study respiratory symptoms and lung function decline in farmers, with particular attention to the influence of handling hay, straw and animal feed.

From a cohort recruited in 1993–1994, 219 (82.6%) dairy farmers, 130 (62.5%) nondairy agricultural workers and 99 (66.4%) controls were re-evaluated in 2006. They answered medical and occupational questionnaires, underwent spirometric tests at both evaluations and pulse oximetry in 2006.

Dairy and nondairy agricultural workers showed an increased risk for usual morning phlegm (adjusted OR 4.27 (95% CI 1.41–12.95) and 3.59 (95% CI 1.16–11.10), respectively). Animal feed handling was associated with increased risks of wheezing (p = 0.01) and usual morning phlegm (p = 0.04); hay or straw handling was associated with increased risk of wheezing (p = 0.008). Adjusting for smoking, age, height, sex and altitude, dairy farmers had greater declines in forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio (p = 0.01) than controls. An increased decline in FEV1for all agricultural workers was associated with animal feed handling, both measured as a categorical (currentlyversusnever handling; p = 0.05) or quantitative value (years of exposure during the survey period; p = 0.03).

Hay, straw or animal feed handling represents a risk factor of bronchial symptoms and, for animal feed only, of accelerated decline in expiratory flows.
Genetic profiling and epidermal growth factor receptor-directed therapy in nonsmall cell lung cancer
Authors: Cadranel J. , Zalcman G. , Sequist L.
Published: October 2010

The principle of preferentially selecting patients most likely to benefit from therapy according to their genetic profile has led to substantial clinical benefit in some tumour types, and has potential to considerably refine treatment in advanced nonsmall cell lung cancer (NSCLC). Effective, reliable use of molecular biomarkers to inform clinical practice requires the standardisation of testing methods and careful assessment of biomarkers’ predictive and prognostic value.

Although a number of studies have shown that patients with activating mutations in exons 18–21 of the epidermal growth factor receptor (EGFR) gene respond particularly well to gefitinib and erlotinib, a prospective, randomised study was needed to differentiate between the prognostic and predictive value ofEGFRmutations. From one such study, it appeared that mutational testing should become standard at diagnosis, at least for adenocarcinoma patients with a never or low smoking history, as clinical predictors are insufficient to optimise treatment.

However, outstanding questions remain: what are the treatment options for patients with tumours resistant to erlotinib/gefitinib? What conclusions about treatment can we draw fromEGFRcopy number orKRASmutation status? What role should anti-EGFR antibodies play in NSCLC treatment, and in which patients?

This review considers current evidence linking biomarker profile to efficacy of EGFR-targeted therapy in NSCLC, and clinical implications of recent findings.
Contrasting population genetic patterns within the white-throated sparrow genome (Zonotrichia albicollis)
Authors: Huynh Lynn Y , Maney Donna L , Thomas James W
Published: October 2010

Background

The level of nucleotide diversity observed across the genome is positively correlated with the local rate of recombination. Avian karyotypes are typified by large variation in chromosome size and the rate of recombination in birds has been shown to be negatively correlated with chromosome size. It has thus been predicted that nucleotide diversity is negatively correlated with chromosome size in aves. However, there is limited empirical evidence to support this prediction.

Results

Here we sequenced 27 autosomal and 12 sex chromosome-linked loci in the white-throated sparrow (Zonotrichia albicollis) to quantify and compare patterns of recombination, linkage disequilibrium (LD), and genetic diversity across the genome of this North American songbird. Genetic diversity on the autosomes varied up to 8-fold, with the lowest diversity observed on the macrochromosomes and the highest diversity on the microchromosomes. Genetic diversity on the sex chromosomes was reduced compared to the autosomes, the most extreme difference being a ~300-fold difference between the W chromosome and the microchromosomes. LD and population structure associated with a common inversion polymorphism (ZAL2/2m) in this species were found to be atypical compared to other macrochromosomes, and nucleotide diversity within this inversion on the two chromosome arrangements was more similar to that observed on the Z chromosome.

Conclusions

A negative correlation between nucleotide diversity and autosome size was observed in the white-throated sparrow genome, as well as low levels of diversity on the sex chromosomes comparable to those reported in other birds. The population structure and extended LD associated with the ZAL2/2m chromosomal polymorphism are exceptional compared to the rest of the white-throated sparrow genome.
Rhomboid homologs in mycobacteria: insights from phylogeny and genomic analysis
Authors: Kateete David P , Okee Moses , Katabazi Fred A , Okeng Alfred , Asiimwe Jeniffer , Boom Henry W , Eisenach Kathleen D , Joloba Moses L
Published: October 2010

Background

Rhomboids are ubiquitous proteins with diverse functions in all life kingdoms, and are emerging as important factors in the biology of some pathogenic apicomplexa andProvidencia stuartii. Although prokaryotic genomes contain one rhomboid, actinobacteria can have two or more copies whose sequences have not been analyzed for the presence putative rhomboid catalytic signatures. We report detailed phylogenetic and genomic analyses devoted to prokaryotic rhomboids of an important genus,Mycobacterium.

Results

Many mycobacterial genomes contained two phylogenetically distinct active rhomboids orthologous to Rv0110 (rhomboid protease 1) and Rv1337 (rhomboid protease 2) ofMycobacterium tuberculosisH37Rv, which were acquired independently. There was a genome-wide conservation and organization of the orthologs of Rv1337 arranged in proximity with glutamate racemase (mur1), while the orthologs of Rv0110 appeared evolutionary unstable and were lost inMycobacterium lepraeand theMycobacterium aviumcomplex. The orthologs of Rv0110 clustered with eukaryotic rhomboids and contained eukaryotic motifs, suggesting a possible common lineage. A novel nonsense mutation at the Trp73 codon split the rhomboid ofMycobacterium aviumsubsp.Paratuberculosisinto two hypothetical proteins (MAP2425c and MAP2426c) that are identical to MAV_1554 ofMycobacterium avium. Mycobacterial rhomboids contain putative rhomboid catalytic signatures, with the protease active site stabilized by Phenylalanine. The topology and transmembrane helices of the Rv0110 orthologs were similar to those of eukaryotic secretase rhomboids, while those of Rv1337 orthologs were unique. Transcription assays indicated that both mycobacterial rhomboids are possibly expressed.

Conclusions

Mycobacterial rhomboids are active rhomboid proteases with different evolutionary history. The Rv0110 (rhomboid protease 1) orthologs represent prokaryotic rhomboids whose progenitor may be the ancestors of eukaryotic rhomboids. The Rv1337 (rhomboid protease 2) orthologs appear more stable and are conserved nearly in all mycobacteria, possibly alluding to their importance in mycobacteria. MAP2425c and MAP2426c provide the first evidence for a split homologous rhomboid, contrasting whole orthologs of genetically related species. Although valuable insights to the roles of rhomboids are provided, the data herein only lays a foundation for future investigations for the roles of rhomboids in mycobacteria.
Plasma concentrations of osteopontin, but not thrombin-cleaved osteopontin, are associated with the presence and severity of nephropathy and coronary artery disease in patients with type 2 diabetes mellitus
Authors: Yan Xiaoxiang , Sano Motoaki , Lu Lin , Wang Wei , Zhang Qi , Zhang Ruiyan , Wang Lingjie , Chen Qiujing , Fukuda Keiichi , Shen Weifeng
Published: October 2010

Background

The aim of the present cross-sectional study was to assess possible associations between osteopontin (OPN), and thrombin-cleaved (N-half) OPN, and nephropathy and coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM).

Methods

Plasma levels of OPN, N-half OPN, and high-sensitivity C-reactive protein (hsCRP) were determined in 301 diabetic patients with (n = 226) or without (n = 75) angiographically documented CAD (luminal diameter narrowing >50%), as well as in 75 non-diabetic controls with normal angiography. The estimated glomerular filtration rate (eGFR) was calculated in all patients.

Results

Plasma levels of OPN and hsCRP were significantly higher in patients with T2DM compared with controls. In addition, there was a higher occurrence of moderate renal insufficiency and lower eGFR in patients with T2DM (all P < 0.01). T2DM patients in whom OPN levels were greater than the median value had higher serum creatinine levels, a greater prevalence of mild or moderate renal insufficiency, a higher incidence of CAD, and lower eGFR (all P < 0.05) than T2DM patients in whom OPN levels were the same as or lower than the median value. However, there were no differences in these parameters when patients were stratified according to plasma N-half OPN levels. Furthermore, there was a significant correlation between OPN, but not N-half OPN, and the severity of nephropathy and CAD in diabetes. After adjustment for potential confounders and treatments, multiple linear regression analysis demonstrated an independent association between OPN, but not N-half OPN, and eGFR. Multivariate logistic regression revealed that higher OPN levels conferred a fourfold greater risk of renal insufficiency and CAD in patients with T2DM.

Conclusions

The results of the present study demonstrate that there is an independent association between plasma levels of OPN, but not N-half OPN, and the presence and severity of nephropathy and CAD in diabetes.