bluuebunny/crossref_metadata_2025 huggingface dataset:
The aging mouse partially models the aging human spine: lumbar and coccygeal disc height, composition, mechanical properties, and Wnt signaling in young and old mice
Authors: Holguin Nilsson , Aguilar Rhiannon , Harland Robin A. , Bomar Bradley A. , Silva Matthew J.
Published: May 2014

Murine lumbar and coccygeal (tail) regions of spines are commonly used to study cellular signaling of age-related disc diseases, but the tissue-level changes of aging intervertebral discs and vertebrae of each spinal region remain unclear. Furthermore, the impact of aging lumbar and coccygeal discs on Wnt/β-catenin signaling, which is putatively involved in the catabolism of intervertebral discs, is also unclear. We compared disc/vertebrae morphology and mechanics and biochemical composition of intervertebral discs from lumbar and coccygeal regions between young (4–5 mo) and old (20–22 mo) female C57BL/6 mice. Center intervertebral disc height from both regions was greater in old discs than young discs. Compared with young, old lumbar discs had a lower early viscous coefficient (a measure of stiffness) by 40%, while conversely old coccygeal discs were stiffer by 53%. Biochemically, old mice had double the collagen content in lumbar and coccygeal discs of young discs, greater glycosaminoglycan in lumbar discs by 37%, but less glycosaminoglycan in coccygeal discs by 32%. Next, we compared Wnt activity of lumbar and coccygeal discs of 4- to 5-mo and 12- to 14-mo TOPGAL mice. Despite the disc-specific changes, aging decreased Wnt signaling in the nucleus pulposus from both spinal regions by ≥64%. Compared with young, trabecular bone volume/tissue volume and ultimate force were less in old lumbar vertebrae, but greater in old coccygeal vertebrae. Thus intervertebral discs and vertebrae age in a spinal region-dependent manner, but these differential age-related changes may be uncoupled from Wnt signaling. Overall, lumbar and coccygeal regions are not interchangeable in modeling human aging.
Age-related structural alterations in human skeletal muscle fibers and mitochondria are sex specific: relationship to single-fiber function
Authors: Callahan Damien M. , Bedrin Nicholas G. , Subramanian Meenakumari , Berking James , Ades Philip A. , Toth Michael J. , Miller Mark S.
Published: May 2014

Age-related loss of skeletal muscle mass and function is implicated in the development of disease and physical disability. However, little is known about how age affects skeletal muscle structure at the cellular and ultrastructural levels or how such alterations impact function. Thus we examined skeletal muscle structure at the tissue, cellular, and myofibrillar levels in young (21–35 yr) and older (65–75 yr) male and female volunteers, matched for habitual physical activity level. Older adults had smaller whole muscle tissue cross-sectional areas (CSAs) and mass. At the cellular level, older adults had reduced CSAs in myosin heavy chain II (MHC II) fibers, with no differences in MHC I fibers. In MHC II fibers, older men tended to have fewer fibers with large CSAs, while older women showed reduced fiber size across the CSA range. Older adults showed a decrease in intermyofibrillar mitochondrial size; however, the age effect was driven primarily by women (i.e., age by sex interaction effect). Mitochondrial size was inversely and directly related to isometric tension and myosin-actin cross-bridge kinetics, respectively. Notably, there were no intermyofibrillar or subsarcolemmal mitochondrial fractional content or myofilament ultrastructural differences in the activity-matched young and older adults. Collectively, our results indicate age-related reductions in whole muscle size do not vary by sex. However, age-related structural alterations at the cellular and subcellular levels are different between the sexes and may contribute to different functional phenotypes in ways that modulate sex-specific reductions in physical capacity with age.
Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone
Authors: Shelton Elaine L. , Ector Gerren , Galindo Cristi L. , Hooper Christopher W. , Brown Naoko , Wilkerson Irene , Pfaltzgraff Elise R. , Paria Bibhash C. , Cotton Robert B. , Stoller Jason Z. , Reese Jeff
Published: May 2014

Failure of the ductus arteriosus (DA) to close at birth can lead to serious complications. Conversely, certain profound congenital cardiac malformations require the DA to be patent until corrective surgery can be performed. In each instance, clinicians have a very limited repertoire of therapeutic options at their disposal - indomethacin or ibuprofen to close a patent DA (PDA) and prostaglandin E1 to maintain patency of the DA. Neither treatment is specific to the DA and both may have deleterious off-target effects. Therefore, more therapeutic options specifically targeted to the DA should be considered. We hypothesized the DA possesses a unique genetic signature that would set it apart from other vessels. A microarray was used to compare the genetic profiles of the murine DA and ascending aorta (AO). Over 4,000 genes were differentially expressed between these vessels including a subset of ion channel-related genes. Specifically, the alpha and beta subunits of large-conductance calcium-activated potassium (BKCa) channels are enriched in the DA. Gain- and loss-of-function studies showed inhibition of BKCachannels caused the DA to constrict, while activation caused DA relaxation even in the presence of O2. This study identifies subsets of genes that are enriched in the DA that may be used to develop DA-specific drugs. Ion channels that regulate DA tone, including BKCachannels, are promising targets. Specifically, BKCachannel agonists like NS1619 maintain DA patency even in the presence of O2and may be clinically useful.
Complement C5a Receptor Facilitates Cancer Metastasis by Altering T-Cell Responses in the Metastatic Niche
Authors: Vadrevu Surya Kumari , Chintala Navin K. , Sharma Sharad K. , Sharma Priya , Cleveland Clayton , Riediger Linley , Manne Sasikanth , Fairlie David P. , Gorczyca Wojciech , Almanza Othon , Karbowniczek Magdalena , Markiewski Maciej M.
Published: May 2014

The impact of complement on cancer metastasis has not been well studied. In this report, we demonstrate in a preclinical mouse model of breast cancer that the complement anaphylatoxin C5a receptor (C5aR) facilitates metastasis by suppressing effector CD8+ and CD4+ T-cell responses in the lungs. Mechanisms of this suppression involve recruitment of immature myeloid cells to the lungs and regulation of TGFβ and IL10 production in these cells. TGFβ and IL10 favored generation of T regulatory cells (Treg) and Th2-oriented responses that rendered CD8+ T cells dysfunctional. Importantly, pharmacologic blockade of C5aR or its genetic ablation in C5aR-deficient mice were sufficient to reduce lung metastases. Depletion of CD8+ T cells abolished this beneficial effect, suggesting that CD8+ T cells were responsible for the effects of C5aR inhibition. In contrast to previous findings, we observed that C5aR signaling promoted Treg generation and suppressed T-cell responses in organs where metastases arose. Overall, our findings indicated that the immunomodulatory functions of C5aR are highly context dependent. Furthermore, they offered proof-of-concept for complement-based immunotherapies to prevent or reduce cancer metastasis. Cancer Res; 74(13); 3454–65. ©2014 AACR.
Paths of Resistance to EGFR Inhibitors: Is NF Enough?
Authors: Maertens Ophélia , Cichowski Karen
Published: May 2014

Summary: Although the majority of patients with EGFR-mutant lung cancer respond well to EGF receptor (EGFR) tyrosine kinase inhibitors (TKI), all patients eventually develop resistance. The mechanism of acquired resistance is still unknown for a considerable subset of cases. This study reveals the NF1 tumor suppressor gene as a new mediator of resistance to EGFR TKIs and provides a mechanistic rationale for developing combination therapies. Cancer Discov; 4(5); 519–21. ©2014 AACR.

See related article by de Bruin et al., p. 606
Affinity Enhancement of Antibodies: How Low-Affinity Antibodies Produced Early in Immune Responses Are Followed by High-Affinity Antibodies Later and in Memory B-Cell Responses
Authors: Eisen Herman N.
Published: May 2014

The antibodies produced initially in response to most antigens are high molecular weight (MW) immunoglobulins (IgM) with low affinity for the antigen, while the antibodies produced later are lower MW classes (e.g., IgG and IgA) with, on average, orders of magnitude higher affinity for that antigen. These changes, often termed affinity maturation, take place largely in small B-cell clusters (germinal center; GC) in lymphoid tissues in which proliferating antigen-stimulated B cells express the highly mutagenic cytidine deaminase that mediates immunoglobulin class-switching and sequence diversification of the immunoglobulin variable domains of antigen-binding receptors on B cells (BCR). Of the large library of BCR-mutated B cells thus rapidly generated, a small minority with affinity-enhancing mutations are selected to survive and differentiate into long-lived antibody-secreting plasma cells and memory B cells. BCRs are also endocytic receptors; they internalize and cleave BCR-bound antigen, yielding peptide–MHC complexes that are recognized by follicular helper T cells. Imperfect correlation between BCR affinity for antigen and cognate T-cell engagement may account for the increasing affinity heterogeneity that accompanies the increasing average affinity of antibodies. Conservation of mechanisms underlying mutation and selection of high-affinity antibodies over the ≈200 million years of evolution separating bird and mammal lineages points to the crucial role of antibody affinity enhancement in adaptive immunity. Cancer Immunol Res; 2(5); 381–92. ©2014 AACR.
Pharmacological Activation of the Melanocortin System Limits Plaque Inflammation and Ameliorates Vascular Dysfunction in Atherosclerotic Mice
Authors: Rinne Petteri , Silvola Johanna M.U. , Hellberg Sanna , Ståhle Mia , Liljenbäck Heidi , Salomäki Henriikka , Koskinen Emilia , Nuutinen Salla , Saukko Pekka , Knuuti Juhani , Saraste Antti , Roivainen Anne , Savontaus Eriika
Published: May 2014

Objective—

Melanocortin peptides have been shown to elicit anti-inflammatory actions and to promote vascular endothelial function by activating type 1 and 3 melanocortin receptors. Here, we addressed whether these favorable properties of melanocortins could reduce atherosclerotic plaque inflammation and improve vasoreactivity in atherosclerotic mice.

Approach and Results—

Low-density lipoprotein receptor–deficient mice expressing only apolipoprotein B100 were fed a high-fat diet for 8 or 16 weeks and treated with either vehicle or a stable melanocortin analog, melanotan II (MT-II, 0.3 mg/kg per day, 4 weeks). We determined plaque uptake of fluorine-18–labeled fluorodeoxyglucose as a surrogate marker for atherosclerotic plaque inflammation and vascular function of the aorta by ex vivo analyses. MT-II had no effect on body weight or composition, or plasma cholesterol levels in atherosclerotic mice. Without attenuating atherosclerotic lesion size or lesional macrophage accumulation, MT-II treatment reduced fluorine-18–labeled fluorodeoxyglucose uptake in the atherosclerotic plaques. Resident macrophages in the lesions of MT-II–treated mice were polarized toward the anti-inflammatory M2 phenotype. Systemic inflammation was also attenuated by MT-II intervention as evidenced by decreased plasma levels of proinflammatory cytokines. In terms of aortic vasoreactivity, MT-II–treated mice showed enhanced endothelium-dependent relaxations, as well as promotion of vascular sensitivity to nitric oxide–mediated vasodilation, which were markedly impaired in control mice after prolonged duration of diet exposure.

Conclusions—

The present study demonstrates that pharmacological activation of the melanocortin system has therapeutic benefits in pre-established atherosclerosis by limiting plaque inflammation and promoting vascular endothelial function, which may provide a novel therapeutic approach for atherosclerosis.
von Willebrand Factor Directly Interacts With DNA From Neutrophil Extracellular Traps
Authors: Grässle Sandra , Huck Volker , Pappelbaum Karin I. , Gorzelanny Christian , Aponte-Santamaría Camilo , Baldauf Carsten , Gräter Frauke , Schneppenheim Reinhard , Obser Tobias , Schneider Stefan W.
Published: May 2014

Objective—

Inflammatory conditions provoke essential processes in the human vascular system. It leads to the formation of ultralarge von Willebrand factor (VWF) fibers, which are immobilized on the endothelial cell surface and transform to highly adhesive strings under shear conditions. Furthermore, leukocytes release a meshwork of DNA (neutrophil extracellular traps) during the process of the recently discovered cell death program NETosis. In the present study, we characterized the interaction between VWF and DNA and possible binding sites to underline the role of VWF in thrombosis and inflammation besides its function in platelet adhesion.

Approach and Results—

Both functionalized surfaces and intact cell layers of human umbilical vein endothelial cells were perfused with isolated, protein-free DNA or leukocytes from whole blood at distinct shear rates. DNA–VWF interaction was monitored using fluorescence microscopy, ELISA-based assays, molecular dynamics simulations, and electrostatic potential calculations. Isolated DNA, as well as DNA released by stimulated leukocytes, was able to bind to shear-activated, but not inactivated, VWF. However, DNA–VWF binding does not alter VWF degradation by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13. Moreover, DNA–VWF interaction can be blocked using unfractionated and low-molecular-weight heparin, and DNA–VWF complexes attenuate platelet binding to VWF. These findings were supported using molecular dynamics simulations and electrostatic calculations of the A1- and A2-domains.

Conclusions—

Our findings suggest that VWF directly binds and immobilizes extracellular DNA released from leukocytes. Therefore, we hypothesize that VWF might act as a linker for leukocyte adhesion to endothelial cells, supporting leukocyte extravasation and inflammation.
Oxidative Modification of Fibrinogen Is Associated With Altered Function and Structure in the Subacute Phase of Myocardial Infarction
Authors: Becatti Matteo , Marcucci Rossella , Bruschi Giulia , Taddei Niccolò , Bani Daniele , Gori Anna Maria , Giusti Betti , Gensini Gian Franco , Abbate Rosanna , Fiorillo Claudia
Published: May 2014

Objective—

Among plasma proteins, fibrinogen represents a major target of oxidative modifications. In patients with post–acute myocardial infarction (6 months after the acute event), fibrinogen oxidation-induced carbonyls and fibrinogen function were estimated using in vitro and ex vivo approaches. Fibrinogen structural features and clot architecture were also explored.

Approach and Results—

In 39 patients with post–acute myocardial infarction and 28 age-, sex-, and risk factor-matched controls, oxidative stress markers (in plasma and in purified fibrinogen fractions), thrombin-catalyzed fibrin polymerization, and plasmin-induced fibrin lysis were estimated. Circular dichroism spectra of purified fibrinogen extracts, electron microscopy, and differential interference contrast microscopy analyses of fibrin clots were also performed. Marked signs of oxidative stress in plasma (
P
<0.01 versus controls) and, correspondingly, an increased extent of fibrinogen carbonylation (3.5-fold over control values;
P
<0.01 versus controls) were observed in patients. Furthermore, fibrinogen fractions purified from patients exhibited significantly reduced clotting ability and decreased susceptibility to plasmin-induced lysis (
P
<0.01 versus controls). Alterations in fibrinogen secondary structure, as suggested by circular dichroism spectroscopy, and in fibrin clot architecture, as analyzed by electron and differential interference contrast microscopy, were also identified.

Conclusions—

Here, we report for the first time that patients with post–acute myocardial infarction present with an overall imbalance in redox status and marked fibrinogen carbonylation associated with altered fibrinogen function, thus suggesting a role for carbonylation as a direct mechanism of fibrinogen function. The observed features occur along with modifications in protein structure and in clot architecture.
Catheter Ablation of Ventricular Arrhythmia in Nonischemic Cardiomyopathy
Authors: Oloriz Teresa , Silberbauer John , Maccabelli Giuseppe , Mizuno Hiroya , Baratto Francesca , Kirubakaran Senthil , Vergara Pasquale , Bisceglia Caterina , Santagostino Giulia , Marzi Alessandra , Sora Nicoleta , Roque Carla , Guarracini Fabrizio , Tsiachris Dimitris , Radinovic Andrea , Cireddu Manuela , Sala Simone , Gulletta Simone , Paglino Gabriele , Mazzone Patrizio , Trevisi Nicola , Bella Paolo Della
Published: May 2014

Background—

The aim was to relate distinct scar distributions found in nonischemic cardiomyopathy with ventricular tachycardia (VT) morphology, late potential distribution, ablation strategy, and outcome.

Methods and Results—

Eighty-seven patients underwent catheter ablation for drug-refractory VT. Based on endocardial unipolar voltage, 44 were classified as predominantly anteroseptal and 43 as inferolateral. Anteroseptal patients more frequently fulfilled diagnostic criteria for dilated cardiomyopathy (64% versus 36%), associated with more extensive endocardial unipolar scar (41 [22–83] versus 9 [1–29] cm
2
;
P
<0.001). Left inferior VT axis was predictive of anteroseptal scar (positive predictive value, 100%) and right superior axis for inferolateral (positive predictive value, 89%). Late potentials were infrequent in the anteroseptal group (11% versus 74%;
P
<0.001). Epicardial late potentials were common in the inferolateral group (81% versus 4%;
P
<0.001) and correlated with VT termination sites (κ=0.667;
P
=0.014), whereas no anteroseptal patient had an epicardial VT termination (
P
<0.001). VT recurred in 44 patients (51%) during a median follow-up of 1.5 years. Anteroseptal scar was associated with higher VT recurrence (74% versus 25%; log-rank
P
<0.001) and redo procedure rates (59% versus 7%; log-rank
P
<0.001). After multivariable analysis, clinical predictors of VT recurrence were electrical storm (hazard ratio, 3.211;
P
=0.001) and New York Heart Association class (hazard ratio, 1.608;
P
=0.018); the only procedural predictor of VT recurrence was anteroseptal scar pattern (hazard ratio, 5.547;
P
<0.001).

Conclusions—

Unipolar low-voltage distribution in nonischemic cardiomyopathy allows categorization of scar pattern as inferolateral, often requiring epicardial ablation mainly based on late potentials, and anteroseptal, which frequently involves an intramural septal substrate, leading to a higher VT recurrence.
Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack
Authors: Kernan Walter N. , Ovbiagele Bruce , Black Henry R. , Bravata Dawn M. , Chimowitz Marc I. , Ezekowitz Michael D. , Fang Margaret C. , Fisher Marc , Furie Karen L. , Heck Donald V. , Johnston S. Claiborne (Clay) , Kasner Scott E. , Kittner Steven J. , Mitchell Pamela H. , Rich Michael W. , Richardson DeJuran , Schwamm Lee H. , Wilson John A.
Published: May 2014

The aim of this updated guideline is to provide comprehensive and timely evidence-based recommendations on the prevention of future stroke among survivors of ischemic stroke or transient ischemic attack. The guideline is addressed to all clinicians who manage secondary prevention for these patients. Evidence-based recommendations are provided for control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke. Recommendations are also provided for the prevention of recurrent stroke in a variety of specific circumstances, including aortic arch atherosclerosis, arterial dissection, patent foramen ovale, hyperhomocysteinemia, hypercoagulable states, antiphospholipid antibody syndrome, sickle cell disease, cerebral venous sinus thrombosis, and pregnancy. Special sections address use of antithrombotic and anticoagulation therapy after an intracranial hemorrhage and implementation of guidelines.
Remote or Extraischemic Intracerebral Hemorrhage—An Uncommon Complication of Stroke Thrombolysis
Authors: Mazya Michael V. , Ahmed Niaz , Ford Gary A. , Hobohm Carsten , Mikulik Robert , Nunes A. Paiva , Wahlgren Nils ,   Scientific Committee of SITS International, Wahlgren Nils , Dávalos Antoni , Ford Gary A. , Grond Martin , Hacke Werner , Hennerici Michael , Kaste Markku , Lees Kennedy R. , Roine Risto , Tatlisumak Turgut , Toni Danilo , Wang K.S. ,   Scientific Committee of Fighting Stroke (Uppdrag Besegra Stroke), Wahlgren Nils , Ahmed Niaz , Castrén Maaret , Eriksson Ulf , Frisén Jonas , Hedin Ulf , Holmin Staffan , Sjöholm Åke , Svensson Mikael , von Euler Mia
Published: May 2014

Background and Purpose—

Intracerebral hemorrhage after treatment with intravenous recombinant tissue-type plasminogen activator for ischemic stroke can occur in local relation to the infarct, as well as in brain areas remote from infarcted tissue. We aimed to describe risk factors, 3-month mortality, and functional outcome in patients with the poorly understood complication of remote intracerebral hemorrhage, as well as local intracerebral hemorrhage.

Methods—

In this study, 43 494 patients treated with intravenous recombinant tissue-type plasminogen activator, with complete imaging data, were enrolled in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) during 2002 to 2011. Baseline data were compared among 970 patients (2.2%) with remote parenchymal hemorrhage (PHr), 2325 (5.3%) with PH, 438 (1.0%) with both PH and PHr, and 39 761 (91.4%) without PH or PHr. Independent risk factors for all hemorrhage types were obtained by multivariate logistic regression.

Results—

Previous stroke (
P
=0.023) and higher age (
P
<0.001) were independently associated with PHr, but not with PH. Atrial fibrillation, computed tomographic hyperdense cerebral artery sign, and elevated blood glucose were associated with PH, but not with PHr. Female sex had a stronger association with PHr than with PH. Functional independence at 3 months was more common in PHr than in PH (34% versus 24%;
P
<0.001), whereas 3-month mortality was lower (34% versus 39%;
P
<0.001).

Conclusions—

Differences between risk factor profiles indicate an influence of previous vascular pathology in PHr and acute large-vessel occlusion in PH. Additional research is needed on the effect of pre-existing cerebrovascular disease on complications of recanalization therapy in acute ischemic stroke.
Long-Term Risk and Predictors of Recurrent Stroke Beyond the Acute Phase
Authors: Pennlert Johanna , Eriksson Marie , Carlberg Bo , Wiklund Per-Gunnar
Published: May 2014

Background and Purpose—

Previous studies have shown heterogeneous results on predictors and rates of stroke recurrence. This study set out to investigate the long-term risk and predictors of recurrent stroke in Northern Sweden 1995 to 2008.

Methods—

In the population-based Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) stroke incidence registry, stroke survivors of either ischemic stroke or intracerebral hemorrhage were followed for recurrent stroke or death. Cox regression was used to identify predictors of stroke recurrence.

Results—

The study comprised 6700 patients and 26 597 person-years. During follow-up, 928 (13.9%) patients had a recurrent stroke. Comparison between the first time period (1995–1998) and the last (2004–2008) showed declined risk of stroke recurrence (hazard ratio, 0.64 [95% confidence interval, 0.52–0.78]). Previous myocardial infarction was less prevalent in the most recent cohort (
P
<0.001). Predictors of stroke recurrence were age (hazard ratio, 1.03 [95% confidence interval, 1.02–1.04]) and diabetes mellitus (hazard ratio, 1.34 [95% confidence interval, 1.15–1.57]). After an index intracerebral hemorrhage (n=815), a major part of recurrent events were ischemic (63%), and compared with the ischemic stroke group (n=5885), a tendency toward lower risk of recurrence was observed.

Conclusions—

Despite declining recurrence rates in this relatively young stroke population, almost one third are either dead or have experienced a second stroke in 5 years.
Varying Correlation Between
18
F-Fluorodeoxyglucose Positron Emission Tomography and Dynamic Contrast-Enhanced MRI in Carotid Atherosclerosis
Authors: Wang Juan , Liu Hongbin , Sun Jie , Xue Hao , Xie Leixing , Yu Shengyuan , Liang Changzai , Han Xu , Guan Zhiwei , Wei Liqun , Yuan Chun , Zhao Xihai , Chen Huijun
Published: May 2014

Background and Purpose—

18
F-fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced MRI have been proposed to quantitatively assess plaque inflammation by probing macrophages and neovessels, respectively. We examined their correlation to study the in vivo relationship between macrophage and neovessel activities in atherogenesis.

Methods—

Forty-one patients (34 men; aged 65±12 years) with a total of 68 carotid plaques (thickness ≥2 mm on ultrasound; 20 symptomatic) were assessed by both
18
F-fluorodeoxyglucose positron emission tomography/computed tomography and dynamic contrast-enhanced MRI within 2 weeks, measured as target-to-background ratio and transfer constant (
K
trans
), respectively.

Results—

Overall, the correlation between target-to-background ratio and
K
trans
was weak and marginal (
r
=0.22;
P
=0.068). They were correlated in the symptomatic plaques (
r
=0.59;
P
=0.006) but not in the asymptomatic plaques (
r
=0.07;
P
=0.625;
P
=0.033 for difference in
r
). Neither target-to-background ratio nor
K
trans
was significantly higher in the symptomatic plaques, but both showed an inverse relationship with time since last neurological event (
r
=−0.94 and −0.69 for target-to-background ratio and
K
trans
, respectively).

Conclusions—

The correlation between
18
F-fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced MRI measurements varied with clinical conditions, pointing to a complex interplay between macrophages and neovessels under different pathophysiological conditions. The moderate correlation shown only in symptomatic plaques indicates the presence of acute plaque inflammation with increased metabolic activity and cytokine production by inflammatory cells.
Information Management professionals working for intelligence organizations: ethics and deontology implications
Authors: Bonilla Diego Navarro
Published: May 2014

Archive and information management experts trained in library science programs are ideal candidates for jobs in intelligence organizations. Their skills, abilities and knowledge are frequently required in at least two well-defined areas: open source information gathering and records management/archival organisation. Under the general overview of the debate between “big data vs. big narrative” this article focuses on the ethical challenges that affect this community of information professionals. As a key component of the so-called “intelligence culture”, it will be also underlined the need for intensifying from our university classrooms the ethical dimension of information exploitation for security and defence purposes. The role played by these information profiles involved in multiple phases of the intelligence production process must be based not only on efficiency and efficacy criteria but also on deontology principles whose benefits are the fortification of democratic practice by intelligence services working in strong legal frameworks designed to guarantee fundamental rights.
Assessing the success of EU-OSCE cooperation: a case of mutualism?
Authors: Paunov Dimitar
Published: May 2014

This paper examines the relationship between the European Union (EU) and the Organization for Security and Co-operation in Europe (OSCE), with a particular focus on the restart in cooperation occurring at the turn of the century. This was due to the rediscovery of the organisations’ common past, shared values, similar goals, the drawing of identical security strategies and an increased field presence in the same regions. The EU-OSCE relationship has not been without its shortcomings, but the successes of the cooperation have outnumbered the various hurdles. Furthermore, the relationship can be classified as a case of mutualism, as both partners have benefited therefrom.
The OSCE and the Moldova-Transdniestria Conflict: Lessons in Mediation and Conflict Management
Authors: Hill William H.
Published: May 2014

The OSCE has been involved in attempts to resolve the Transdniestrian conflict since 1992, even before the conference became a formal organization. As is the case with other conflicts, the OSCE has often been criticized in Moldova for failure to resolve the conflict. Such criticism, however, often glosses over the positive impact OSCE missions have had on mediation processes, the Moldova-Transdniestria conflict in particular.
“Is Hizmet Liberal?” Mediations and Disciplines of Islam and Liberalism among Gülen Organizations in Istanbul
Authors: Walton Jeremy F.
Published: May 2014

Is Hizmet liberal? The question is intractable both for Hizmet actors and for the Turkish public sphere more broadly. In this essay, I marshal ethnographic research carried out over several years among Hizmet institutions in Istanbul to shed light on the politics of this question. I examine several characteristic Hizmet institutions in order to argue that Hizmet forges a synthesis between Islamic and liberal discourses and practices. This synthesis unravels dichotomous images of Islam and liberalism as necessarily opposed. In particular, I analyze ethical values such as “positive action” (müspet hareket), “service” (hizmet), and piety (taqwa), as well as initiatives, such as interreligious dialogue (dinler arası diyalog), carried out by Hizmet-affiliated charitable foundations/pious endowments (vakıflar). By way of conclusion, I reevaluate the title question of the article to unpack the dialectical tension embedded between liberal political projects and liberalism as a disciplining power.
The Netherlands and the Gülen movement
Authors: van Bruinessen Martin
Published: May 2014

The Gülen movement has been active among immigrant workers from Turkey in the Netherlands since the 1980s. Its first institutions—educational centers, boarding houses, schools, business associations—were established when a (partly) Dutch-educated second generation came to adulthood in the mid-1990s. Ağabeyler (“older brothers”) dispatched from Turkey remained in the background, while students and graduates of Dutch universities and colleges built up support networks in Dutch civil society and municipal administrations, finding official endorsement as well as subsidies for some of their initiatives. They encountered increasing opposition from a coalition of Kemalist and former leftist Turks and anti-Muslim Dutch politicians and journalists, reflecting changing attitudes towards Islam in Dutch popular discourse as well as power struggles in Turkey. Activities that had previously been praised and supported by Dutch counterparts, such as homework assistance centers, dormitories, and (secular) schools came under suspicion when public opinion was alerted that these were the initiatives of a non-transparent Muslim piety movement. In response to negative publicity that accused these schools of brainwashing and Islamic indoctrination, and to prove that it made positive contributions to social integration, the movement closed its dormitories for secondary school students. This was followed by intensified efforts to show success in secular ventures. The result turned the Gülen movement into arguably the most successfully integrated immigrant-based organization in the country.
Said Nursi’s Notion of ‘Sacred Science’: Its Function and Application in Hizmet High School Education
Authors: Tee Caroline , Shankland David
Published: May 2014

This paper explores the teaching of natural science subjects in high schools associated with the Gülen-Hizmet movement in Turkey. It focuses on the apparent reconciliation of scientific learning in a pervasive, albeit unofficial, Sunni Islamic religious culture. The framework for such an accommodation is found in the teachings of Fethullah Gülen and his predecessor, Said Nursi. Following Nursi, Gülen encourages scientific pursuit, and intellectual knowledge in general, as a pious and spiritually meritorious act. Drawing on fieldwork conducted at two Hizmet-affiliated high schools in Turkey, this article explores the “sanctification” of science and learning in the Gülen Movement by highlighting the principle of fedakarlık (self-sacrifice), as the primary motivation of the teaching staff. Focusing also on the schools’ highly disciplined and competitive learning environments (as exemplified in preparations for the prestigious International Science Olympiads), the article suggests that although teacher commitment and prestigious competitive awards bolster the Hizmet schools’ market competitiveness, they fail in actually producing students who pursue careers in natural science fields. By contrast, this article concludes that the movement’s engagement with science, at least at present, is less interested in furthering scientific inquiry than it is in equipping what Gülen has called a ‘Golden Generation’ with the tools it needs to compete with secularist rivals in Turkey.*
Translocal Ethics: Hizmet Teachers and the Formation of Gülen-inspired Schools in Urban Tanzania
Authors: Dohrn Kristina
Published: May 2014

The Gülen Movement (GM) is one of the most dynamic religiously inspired movements in the world today. Constituting a globally active, translocal community with a strong center in Turkey, GM-affiliated actors are primary players in shaping the educational landscapes of countries around the world. The emergence of Gülen-inspired schools (GISs) in urban Tanzania is reflective of the GM’s global reach. Different from other faith-based educational institutions, GISs like Feza Schools in Dar es Salaam do not explicitly promote Islam. However, an Islamic belief and conduct is the base on which actors of the Gülen Movement shape their lives as teachers or administrators in school, as well as the background for founding and supporting them. Hizmet teachers at the Feza Girls’ Secondary and High School (FGSHS) are translating the Islamic background of the GM’s educational engagement into a moral formation of the students that is framed in universal terms. Looking at the teachers’ translocal practices and motivations, it becomes clear that at GISs religion, ethics, and education are closely intertwined.
Laryngopharyngeal Reflux
Authors: Gooi Zhen , Ishman Stacey L. , Bock Jonathan M. , Blumin Joel H. , Akst Lee M.
Published: May 2014

Objective:

This study aimed to describe current patterns for diagnosis and treatment of laryngopharyngeal reflux (LPR) and analyze differences between laryngologists and non-laryngologists.

Methods:

American Academy of Otolaryngology–Head and Neck Surgery and American Broncho-Esophagological Association members were invited to complete an online survey regarding evaluation, diagnosis, and treatment of LPR. Subgroup analysis was performed to identify differences between respondents who completed laryngology fellowships (LF) and those who did not (NL).

Results:

Of 159 respondents, 40 were LF. Video documentation of laryngopharyngeal exams was almost universal among LF (97% vs 38%, P < .0001). Use of rigid (100%, P = .002) and flexible distal-chip technologies (94%, P = .004) was more common among LF. Diagnostic criteria were similar between the groups, with symptoms of heartburn, globus, and throat clearing thought most suggestive of LPR. Adjunctive tests most commonly used were barium esophagram and dual-probe pH testing with impedance. Laryngology fellowship-trained respondents used dual pH probes with impedance more often ( P = .004). They were more likely to prescribe twice daily proton pump inhibitors with concurrent H2-blocker medication initially ( P = .004) and to treat for longer than 4 weeks ( P = .0003).

Conclusion:

Otolaryngologists are in agreement on symptoms and physical features of LPR; however, significant differences exist between laryngologists and non-laryngologists on the use of adjunctive testing and treatment strategies.
Evaluation of Operation RESET: An initiative for addressing child sexual abuse in Aboriginal communities
Authors: Mace Glenn , Powell Martine B , Benson Mairi
Published: May 2014

This paper presents a qualitative evaluation of Operation RESET: a multi-agency child protection strategy for remote Western Australian Aboriginal communities. RESET is a proactive engagement strategy involving a mobile multi-disciplinary specialist child abuse team comprising detectives and social workers. It is underpinned by the principles that preventing and responding to child sexual abuse must be a shared responsibility, address the underlying causes and contextual issues and enhance children's safety and well-being by empowering families and communities. The evaluation procedure consisted of in-depth interviews with 64 stakeholders of various backgrounds and affiliations who lived or worked in regions where RESET had been deployed for the past 18 months. Collectively, the interviews revealed strong support for Operation RESET's implementation and outcomes. Stakeholders highlighted four elements as being valuable components of the reform: the programme's proactive outreach approach, dedication to capacity building, holistic focus and the establishment of relationships that facilitated trust. These findings are discussed within the broader literature and suggestions for further research are offered.
Beyond the ‘sext’: Technology-facilitated sexual violence and harassment against adult women
Authors: Henry Nicola , Powell Anastasia
Published: May 2014

Young people's use of technology as a tool for the negotiation of their sexual identities and encounters has increasingly become a focal point in popular and scholarly discussion. Much of this debate centres on the sending of explicit sexual images and/or video (‘selfies’ or ‘sexting’) by mobile phone, email or social media. In Australia and elsewhere, legislative frameworks have arguably over-regulated or criminalised young people's consensual, digital, sexual communications. Equally, the law has failed to respond to the harm that is experienced by victims of non-consensual making and/or distribution of such sexual images. In this paper, we examine the non-consensual creation and distribution of sexual images in the context of harassment, stalking and family or intimate violence. We argue that harmful digital communications are often framed as a problem of user naiveté rather than gender-based violence. Moreover, we argue that current legal and policy approaches fail to adequately capture the social and psychological harm that results from the use of sexual imagery to harass, coerce or blackmail women. We draw on preliminary data from a larger project investigating adult women's experiences of technology-mediated sexual violence and harassment.
The Effect of Saccadic Training on Early Reading Fluency
Authors: Leong Danielle F. , Master Christina L. , Messner Leonard V. , Pang Yi , Smith Craig , Starling Amaal J.
Published: May 2014

Background. Eye movements are necessary for the physical act of reading and have been shown to relate to underlying cognitive and visuoattentional processes during reading. The purpose of this study was to determine the effect of saccadic training using the King-Devick remediation software on reading fluency. Methods. In this prospective, single-blinded, randomized, crossover trial, a cohort of elementary students received standardized reading fluency testing pre- and posttreatment. Treatment consisted of in-school training 20 minutes per day, 3 days per week for 6 weeks. Results. The treatment group had significantly higher reading fluency scores after treatment ( P < .001), and posttreatment scores were significantly higher than the control group ( P < .005). Conclusion. Saccadic training can significantly improve reading fluency. We hypothesize that this improvement in reading fluency is a result of rigorous practice of eye movements and shifting visuospatial attention, which are vital to the act of reading.
Sudden Hearing Loss in Children
Authors: Ječmenica Jovana , Bajec-Opančina Aleksandra
Published: May 2014

Sudden sensorineural hearing loss (SSHL) is defined as a unilateral or bilateral sensorineural hearing loss with at least 30 dB decrease in threshold in 3 contiguous test frequencies occurring over 72 hours or less. It is very rare in children. Sudden hearing loss is a symptom that suggests that there is a problem in the inner ear, surrounding structures, or the whole organism. The etiology and development of this disorder are still not fully understood. The literature contains numerous models of the pathogenesis of SSHL, with childhood SSHL having certain peculiarities. In practical terms, the multifactorial nature of SSHL is important in the choice of diagnostic methods and treatment methods. It is important to determine the cause and effect relationship between the underlying disease and hearing loss.
Transformational Strategy or Gilded Pacification? Four Years On: The Niger Delta Armed Conflict and the DDR Process of the Nigerian Amnesty Programme
Authors: Agbiboa Daniel E
Published: May 2014

My central aim in this paper is to evaluate the outcomes of the amnesty programme established in mid-2009 by the Nigerian government as a way of resolving the groundswell of violence in the oil-rich Niger Delta region. In particular, I focus analytic attention on the planning and implementation of the Disarmament, Demobilisation and Reintegration (DDR) process of the amnesty. I argue that while the amnesty promotes non-killing alternatives to conflict resolution and opens a door for stabilisation, its current planning and implementation is flawed and unable to reduce the long-term potential for armed conflict in the Niger Delta. Far from been a transformational strategy, I argue that the amnesty programme has become a strategy of gilded pacification essentially targeted at buying off militants and re-establishing oil and gas production in the Niger Delta without addressing the multilayered causes of peacelessness in the region.
The event of absolute freedom
Authors: Ciavatta David
Published: May 2014

It is argued that the critique of the French Revolution that Hegel develops in the Phenomenology of Spirit can be fruitfully understood as exposing the problematic relationship that the revolution had to its own character as an historical event. Hegel’s critique of the revolution’s operative commitment to an abstract, ahistorical rationality is explored by way of a study of the significance of the revolutionaries’ attempt to institute a radical new calendar system: it is argued that the Republican Calendar provides an exemplary case for understanding the particular nature of the tension Hegel identifies between the domain of historical particularity and eventfulness, on the one hand, and the universal, timeless character of abstract reason, on the other.
TV Viewing, Perceived Similarity, Coviewing, and Mental Well-Being Among African American, Latino, and White Children
Authors: McDade-Montez Elizabeth , Wallander Jan , Elliott Marc , Grunbaum Jo Anne , Tortolero Susan , Cuccaro Paula , Schuster Mark A.
Published: May 2014

Research among adults has demonstrated concurrent and prospective negative associations between TV viewing and mental health, yet little research has examined these associations among African American and Latino youth or examined the role of children’s involvement with TV and parental mediation of TV viewing via coviewing. The purpose of the present study is to examine associations between TV viewing, perceived similarity, and coviewing and mental well-being in African American, Latino, and White children. Results from Healthy Passages™, a study of 4,824 African American (30%), Latino (47%), and White (23%) fifth graders, indicated that TV viewing and perceived similarity were negatively associated with mental well-being among most groups of children, and coviewing was positively associated with mental well-being among Latinos. This study extends findings from adult research on media exposure and mental well-being into a diverse sample of fifth graders and illuminates the role of perceived similarity and coviewing.
Quadrupedal locomotion using hierarchical operational space control
Authors: Hutter Marco , Sommer Hannes , Gehring Christian , Hoepflinger Mark , Bloesch Michael , Siegwart Roland
Published: May 2014

This paper presents the application of operational space control based on hierarchical task optimization for quadrupedal locomotion. We show how the behavior of a complex robotic machine can be described by a simple set of least squares problems with different priorities for motion, torque, and force optimization. Using projected dynamics of floating base systems with multiple contact points, the optimization dimensionality can be reduced or decoupled such that the formulation is purely based on the inversion of kinematic system properties. The present controller is extensively tested in various experiments using the fully torque controllable quadrupedal robot StarlETH. The load distribution is optimized for static walking gaits to improve contact stability and/or actuator efficiency under various terrain conditions. This is augmented with simultaneous joint position and torque limitations as well as with an interpolation method to ensure smooth contact transitions. The same control structure is further used to stabilize dynamic trotting gaits under significant external disturbances such as uneven ground or pushes. To the best of our knowledge, this work is the first documentation of static and dynamic locomotion with pure task-space inverse dynamics (no joint position feedback) control.
Design and experimental implementation of a hybrid zero dynamics-based controller for planar bipeds with curved feet
Authors: Martin Anne E. , Post David C. , Schmiedeler James P.
Published: May 2014

This paper extends the use of virtual constraints and hybrid zero dynamics (HZD), a successful control strategy for point-foot bipeds, to the design of controllers for planar curved foot bipeds. Although the rolling contact constraint at the foot–ground interface increases complexity somewhat, the measure of local stability remains a function of configuration only, and a closed-form solution still determines the existence of a periodic orbit. The formulation is validated in experiment using the planar five-link biped ERNIE. While gaits designed for point feet yielded stable walking when ERNIE was equipped with curved feet, errors in both desired speed and joint tracking were significantly larger than for gaits designed for the correct radius curved feet. Thus, HZD-based control of this biped is shown to be robust to some modeling error in the foot radius, but at the same time, to require consideration of foot radius to achieve predictably reliable walking gaits. Additionally, under HZD-based control, this biped walked with lower specific energetic cost of transport and joint tracking errors for matched curved foot gait design and hardware compared to matched point-foot gait design and hardware.