bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and bone resorption evaluation of a novel Cathepsin K inhibitor (VEL‐0230) in healthy adult horses
Authors: Hussein H. , Ishihara A. , Menendez M. , Bertone A. 
Published: April 2014

Plasma pharmacokinetic (PK) and bone resorption biomarker [carboxy‐terminal cross‐linking telopeptide of type I collagen (CTX‐1)] analyses were performed following single and multiple oral dose protocols of a Cathepsin K inhibitor (VEL‐0230) in horses. Outcomes included plasma and urine drug and CTX‐1 concentrations. In the dose range study, 2, 4, and 8 mg/kg body weight (b.w.) doses were administered in a Latin square design to three mares and evaluated for 1 week. Based on the PK characteristics of VEL‐0230, 4 mg/kg b.w. was selected for the dose interval study in which 3.25 days (d) and 7 days dose intervals were evaluated over three administrations using four exercising horses in a Latin square design. The 3.25 days and 7 days dose intervals provided a rapid inhibition of bone resorption based on plasma CTX‐1. CTX‐1 inhibition prior to next dose administration was not different from baseline in the 3.25 days and 7 days protocols, and for the first 3 days but the sustained CTX‐1 inhibition in the 7 days protocol along with the cost and logistic benefits for weekly administration made the 7 days protocol preferable. Weekly administration of VEL‐0230 may provide effective inhibition of bone resorption in young exercising horses that returns to baseline within 7 days after drug withdrawal even after multiple doses.
Phosphorylation of Bacillus subtilis gene regulator AbrB modulates its DNA‐binding properties
Authors: Kobir Ahasanul , Poncet Sandrine , Bidnenko Vladimir , Delumeau Olivier , Jers Carsten , Zouhir Samira , Grenha Rosa , Nessler Sylvie , Noirot Phillipe , Mijakovic Ivan 
Published: April 2014

SummaryAbrB is a global gene regulator involved in transition phase phenomena in Bacillus subtilis. It participates in a complex regulatory network governing the expression of stationary‐phase functions. AbrB was previously found to be phosphorylated on serine 86 located close to its C‐terminal oligomerization domain. Here we report that AbrB can be phosphorylated by three B. subtilis serine/threonine kinases expressed during the transition and stationary phase: PrkC, PrkD and YabT. Our in vitro findings suggest that AbrB phosphorylation impedes its DNA binding and abolishes binding cooperativity. In vivo we established that a phospho‐mimetic mutation abrB S86D leads to a significant loss of AbrB control over several key target functions: exoprotease production, competence development and sporulation. A wider transcriptome analysis of abrB S86D and S86A mutant strains revealed deregulation of a large number of target genes. We therefore propose that AbrB phosphorylation serves as an additional input for fine‐tuning the activity of this ambiactive gene regulator.
Fatty acids and stable isotopes (δ13C and δ15N) reveal temporal changes in narwhal (Monodon monoceros) diet linked to migration patterns
Authors: Watt Cortney A. , Ferguson Steven H. 
Published: April 2014

AbstractNarwhals (Monodon monoceros) are sentinel species in the Arctic and to investigate marine food web changes from 1982–2011 we examined diet using fatty acids, δ15N, and δ13C, in narwhals from Baffin Bay (BB) and northern Hudson Bay (NHB). We predicted temporal changes would be greater inNHBdue to a significant reduction in summer ice cover. InNHB, δ15N significantly increased, δ13C displayed a parabolic trend, and fatty acids gradually shifted, albeit not significantly, over time. δ15N was stable, δ13C decreased, and fatty acids significantly changed over time inBB. Stable isotope mixing models indicated a dietary reduction in capelin and increase in Greenland halibut from 1994–2000 to 2006–2011 inBB, while capelin was an important dietary component for narwhals inNHBin recent years (2006–2011). These dietary changes may be attributed to changes in sea ice and narwhal migration. Seasonal dietary changes, as evidenced by changes in blubber fatty acids and skin and muscle stable isotopes, were not as apparent in theNHBpopulation, which may be indicative of a reduced migratory distance. Long‐term monitoring of narwhal diet and migratory patterns associated with reduced sea ice provides invaluable information about how the marine ecosystem will redistribute with global warming.
Worldwide Mutinies Against Globalization
Authors: MISHRA PANKAJ 
Published: April 2014

As the world shifts from American‐led Globalization 1.0 to 2.0—an interdependence of plural identities where no one country or group of nations is at the helm—a vacuum is forming. The intellectual hegemony of Western ideas of development and society no longer prevail, but new models are yet to be found.In the wake of this vacuum, we are witnessing, as Pankaj Mishra writes, worldwide “mutinies” against the old order along with a surge of nationalism and xenophobia that is looking to imagined organic unities of the past, as Elif Shafak writes. What fresh, non‐global ideologies might emerge? Or might a new hybrid cosmopolitan path that doesn't erase plural identities, but erases boundaries that close off instead of open up, create new opportunities for a peaceful and richer global civilization?
The Urgency of a Cosmopolitan Ideal as Nationalism Surges
Authors: SHAFAK ELIF 
Published: April 2014

As the world shifts from American‐led Globalization 1.0 to 2.0—an interdependence of plural identities where no one country or group of nations is at the helm—a vacuum is forming. The intellectual hegemony of Western ideas of development and society no longer prevail, but new models are yet to be found.In the wake of this vacuum, we are witnessing, as Pankaj Mishra writes, worldwide “mutinies” against the old order along with a surge of nationalism and xenophobia that is looking to imagined organic unities of the past, as Elif Shafak writes. What fresh, non‐global ideologies might emerge? Or might a new hybrid cosmopolitan path that doesn't erase plural identities, but erases boundaries that close off instead of open up, create new opportunities for a peaceful and richer global civilization?
China's Long‐Range Salami Tactics In East Asia
Authors: CHANDA NAYAN 
Published: April 2014

Despite grand visions of a cosmopolitan planet living in peace, the first globalization at the turn of the 20th century descended into World War I as the old empires scrambled to preserve themselves as others sought self‐determination. Powers on the losing end of that war reasserted themselves in yet another worldwide calamity within decades.After World War II, in the early 1950s, with the victorious American‐led alliance in the driver's seat, institutions such as the United Nations and the Bretton Woods arrangements created a global stability that enabled peace, prosperity and the “rise of the rest.”In 2014, the world order is shifting again with the rise of China reviving in Asia the very kind of nationalist rivalries that led Europe to war twice in the 20th century.Will we be able to build new institutions that accommodate the new powershift without resorting to war, or will the second globalization collapse as well? Top strategists from the US, Japan and China respond to this momentous question.
Where in the World Will China Invest Its Billions?
Authors: XUEDONG DING 
Published: April 2014

Despite grand visions of a cosmopolitan planet living in peace, the first globalization at the turn of the 20th century descended into World War I as the old empires scrambled to preserve themselves as others sought self‐determination. Powers on the losing end of that war reasserted themselves in yet another worldwide calamity within decades.After World War II, in the early 1950s, with the victorious American‐led alliance in the driver's seat, institutions such as the United Nations and the Bretton Woods arrangements created a global stability that enabled peace, prosperity and the “rise of the rest.”In 2014, the world order is shifting again with the rise of China reviving in Asia the very kind of nationalist rivalries that led Europe to war twice in the 20th century.Will we be able to build new institutions that accommodate the new powershift without resorting to war, or will the second globalization collapse as well? Top strategists from the US, Japan and China respond to this momentous question.
Significance of the melanocortin 1 receptor in the DNA damage response of human melanocytes to ultraviolet radiation
Authors: Swope Viki , Alexander Christina , Starner Renny , Schwemberger Sandy , Babcock George , Abdel‐Malek Zalfa A. 
Published: April 2014

SummaryActivation of the melanocortin 1 receptor (MC1R) by α‐melanocortin (α‐MSH) stimulates eumelanin synthesis and enhances repair of ultraviolet radiation (UV)‐induced DNA damage. We report on the DNA damage response (DDR) of human melanocytes to UV and its enhancement by α‐MSH. α‐MSH up‐regulated the levels of XPC, the enzyme that recognizes DNA damage sites, enhanced the UV‐induced phosphorylation of the DNA damage sensors ataxia telangiectasia and Rad3‐related (ATR) and ataxia telangiectasia mutated (ATM) and their respect‐ive substrates checkpoint kinases 1 and 2, and increased phosphorylated H2AX (γH2AX) formation. These effects required functional MC1R and were absent in melanocytes expressing loss of function (LOF) MC1R. The levels of wild‐type p53‐induced phosphatase 1 (Wip1), which dephosphorylates γH2AX, correlated inversely with γH2AX. We propose that α‐MSH increases UV‐induced γH2AX to facilitate formation of DNA repair complexes and repair of DNA photoproducts, and LOF of MC1R compromises the DDR and genomic stability of melanocytes.
Ptosis during hematologic malignancy in children
Authors: Ekici Arzu , Yakut Ayten , Bör Özcan , Yimenicioğlu Sevgi , Çarman Kürşat Bora , Saylısoy Suzan 
Published: April 2014

AbstractNeurological symptoms such as ptosis may develop due to either chemotherapeutic agents or involvement of the central nervous system (CNS) during hematologic malignancy. It is difficult to make this distinction according to clinical symptoms and magnetic resonance imaging findings. If the neurologic symptoms are increased, it is a warning of CNS involvement. Herein are described the clinical and neuroimaging features of three patients with hematologic malignancy who presented with ptosis.
Emergency coronary artery bypass grafting for cardiogenic shock due to left main coronary artery obstruction caused by Kawasaki disease in a 4‐year‐old boy
Authors: Tamaki Wataru , Tsuda Etsuko , Nakajima Hiroyuki , Kobayashi Junjiro , Shiono Junko 
Published: April 2014

AbstractWe describe the case of a 4‐year‐old boy whose clinical course after Kawasaki disease resulted in coronary artery bypass grafting (CABG) due to acute myocardial infarction (AMI) causing cardiogenic shock. He had developed an ischemic cardiomyopathy due to severe localized stenosis of the left main coronary artery (LCA) and went into cardiogenic shock due to AMI on the day before a scheduled operation. He underwent successful emergency CABG within 4 h of MI. Postoperatively his neurological status was intact. This is the first report of a successful emergency CABG in a small child with cardiogenic shock due to LCA occlusion. CABG should be undertaken in small patients when appropriate indications exist, if bodyweight is >10 kg.
Biotin and carnitine deficiency due to hypoallergenic formula nutrition in infants with milk allergy
Authors: Hayashi Hisako , Tokuriki Shuko , Okuno Takashi , Shigematsu Yosuke , Yasushi Akiba , Matsuyama Go , Sawada Ken , Ohshima Yusei 
Published: April 2014

AbstractAmino acid formulas and hydrolyzed formulas given to infants in Japan with milk allergies theoretically contain little, if any, biotin and carnitine. We assessed biotin and carnitine insufficiency in six infants with milk allergy who were fed amino acid formulas and/or hydrolyzed formulas, by measuring urine 3‐hydroxyisovaleric acid (3‐HIA) and serum free carnitine (C0), respectively. All patients presented with elevated urine 3‐HIA and lowered serum C0 compared with post‐menstrual age‐matched infants who were fed breast milk or standard infant formulas. Supplementation with biotin and l‐carnitine immediately improved the insufficiency. Care should be taken to avoid biotin and carnitine deficiency in allergic infants fed amino acid or hydrolyzed formulas.
Enhancing a Geographic Regression Discontinuity Design Through Matching to Estimate the Effect of Ballot Initiatives on Voter Turnout
Authors: Keele Luke , Titiunik Rocío , Zubizarreta José R. 
Published: April 2014

SummaryBallot initiatives allow the public to vote directly on public policy. The literature in political science has attempted to document whether the presence of an initiative can increase voter turnout. We study this question for an initiative that appeared on the ballot in 2008 in Milwaukee, Wisconsin, using a natural experiment based on geography. This form of natural experiment exploits variation in geography where units in one geographic area receive a treatment whereas units in another area do not. When assignment to treatment via geographic location creates as-if random variation in treatment assignment, adjustment for baseline covariates is unnecessary. In many applications, however, some adjustment for baseline covariates may be necessary. As such, analysts may wish to combine identification strategies—using both spatial proximity and covariates. We propose a matching framework to incorporate information about both geographic proximity and observed covariates flexibly which allows us to minimize spatial distance while preserving balance on observed covariates. This framework is also applicable to regression discontinuity designs that are not based on geography. We find that the initiative on the ballot in Milwaukee does not appear to have increased turnout.
Solving Multimodal Paradoxes
Authors: Pailos Federico , Rosenblatt Lucas 
Published: April 2014

AbstractRecently, it has been observed that the usual type‐theoretic restrictions are not enough to block certain paradoxes involving two or more predicates. In particular, when we have a self‐referential language containing modal predicates, new paradoxes might appear even if there are type restrictions for the principles governing those predicates. In this article we consider two type‐theoretic solutions to multimodal paradoxes. The first one adds types for each of the modal predicates. We argue that there are a number of problems with most versions of this approach. The second one, which we favour, represents modal notions by using the truth predicate together with the corresponding modal operator. This way of doing things is not only useful because it avoids multimodal paradoxes, but also because it preserves the expressive capacity of the language. As an example of the sort of theory we have in mind, we provide a type‐theoretic axiomatization that combines truth with necessity and knowledge.
Evaluating Aid for Trade: A Survey of Recent Studies
Authors: Cadot Olivier , Fernandes Ana , Gourdon Julien , Mattoo Aaditya , de Melo Jaime 
Published: April 2014

AbstractThe demand for accountability in ‘Aid‐for‐Trade’ (AFT) is increasing but monitoring has focused on case studies and impressionistic narratives. The paper reviews recent evidence from a wide range of studies, recognising that a multiplicity of approaches is needed to learn what works and what does not. The review concludes that there is some support for the emphasis on reducing trade costs through investments in hard infrastructure (like ports and roads) and soft infrastructure (like customs). But failure to implement complementary reform – especially the introduction of competition in transport services – may erode the benefits of these investments. Direct support to exporters does seem to lead to diversification across products and destinations, but it is not yet clear that these benefits are durable. In general, it is difficult to rely on cross‐country studies to direct AFT. More rigorous impact evaluation is an under‐utilised alternative, but situations of ‘clinical interventions’ in trade are rare and adverse incentives (due to agency problems) and costs (due to the small size of project) are a hurdle in implementation.
Importance of Multidrug Efflux Pumps in the Antimicrobial Resistance Property of Clinical Multidrug-Resistant Isolates of Neisseria gonorrhoeae
Authors: Golparian Daniel , Shafer William M. , Ohnishi Makoto , Unemo Magnus 
Published: April 2014

ABSTRACT

The contribution of drug efflux pumps in clinical isolates of
Neisseria gonorrhoeae
that express extensively drug-resistant or multidrug-resistant phenotypes has heretofore not been examined. Accordingly, we assessed the effect on antimicrobial resistance of loss of the three gonococcal efflux pumps associated with a known capacity to export antimicrobials (MtrC-MtrD-MtrE, MacA-MacB, and NorM) in such clinical isolates. We report that the MIC of several antimicrobials, including seven previously and currently recommended for treatment was significantly impacted.
Significance and Clinical Management of Persistent Low-Level Viremia and Very-Low-Level Viremia in HIV-1-Infected Patients
Authors: Ryscavage Patrick , Kelly Sean , Li Jonathan Z. , Harrigan P. Richard , Taiwo Babafemi 
Published: April 2014

ABSTRACTA goal of HIV therapy is to sustain suppression of the plasma viral load below the detection limits of clinical assays. However, widely followed treatment guidelines diverge in their interpretation and recommended management of persistent viremia of low magnitude, reflecting the limited evidence base for this common clinical finding. Here, we review the incidence, risk factors, and potential consequences of low-level HIV viremia (LLV; defined in this review as a viremia level of 50 to 500 copies/ml) and very-low-level viremia (VLLV; defined as a viremia level of <50 copies/ml detected by clinical assays that have quantification cutoffs of <50 copies/ml). Using this framework, we discuss practical issues related to the diagnosis and management of patients experiencing persistent LLV and VLLV. Compared to viral suppression at <50 or 40 copies/ml, persistent LLV is associated with increased risk of antiretroviral drug resistance and overt virologic failure. Higher immune activation and HIV transmission may be additional undesirable consequences in this population. It is uncertain whether LLV of <200 copies/ml confers independent risks, as this level of viremia may reflect assay-dependent artifacts or biologically meaningful events during suppression. Resistance genotyping should be considered in patients with persistent LLV when feasible, and treatment should be modified if resistance is detected. There is a dearth of clinical evidence to guide management when genotyping is not feasible. Increased availability of genotypic assays for samples with viral loads of <400 copies/ml is needed.
Predictive Models for Identification of Hospitalized Patients Harboring KPC-Producing Klebsiella pneumoniae
Authors: Tumbarello Mario , Trecarichi Enrico Maria , Tumietto Fabio , Del Bono Valerio , De Rosa Francesco Giuseppe , Bassetti Matteo , Losito Angela Raffaella , Tedeschi Sara , Saffioti Carolina , Corcione Silvia , Giannella Maddalena , Raffaelli Francesca , Pagani Nicole , Bartoletti Michele , Spanu Teresa , Marchese Anna , Cauda Roberto , Viscoli Claudio , Viale Pierluigi 
Published: April 2014

ABSTRACT

The production of
Klebsiella pneumoniae
carbapenemases (KPCs) by
Enterobacteriaceae
has become a significant problem in recent years. To identify factors that could predict isolation of KPC-producing
K. pneumoniae
(KPCKP) in clinical samples from hospitalized patients, we conducted a retrospective, matched (1:2) case-control study in five large Italian hospitals. The case cohort consisted of adult inpatients whose hospital stay included at least one documented isolation of a KPCKP strain from a clinical specimen. For each case enrolled, we randomly selected two matched controls with no KPCKP-positive cultures of any type during their hospitalization. Matching involved hospital, ward, and month/year of admission, as well as time at risk for KPCKP isolation. A subgroup analysis was also carried out to identify risk factors specifically associated with true KPCKP infection. During the study period, KPCKP was isolated from clinical samples of 657 patients; 426 of these cases appeared to be true infections. Independent predictors of KPCKP isolation were recent admission to an intensive care unit (ICU), indwelling urinary catheter, central venous catheter (CVC), and/or surgical drain, ≥2 recent hospitalizations, hematological cancer, and recent fluoroquinolone and/or carbapenem therapy. A Charlson index of ≥3, indwelling CVC, recent surgery, neutropenia, ≥2 recent hospitalizations, and recent fluoroquinolone and/or carbapenem therapy were independent risk factors for KPCKP infection. Models developed to predict KPCKP isolation and KPCKP infection displayed good predictive power, with the areas under the receiver-operating characteristic curves of 0.82 (95% confidence interval [CI], 0.80 to 0.84) and 0.82 (95% CI, 0.80 to 0.85), respectively. This study provides novel information which might be useful for the clinical management of patients harboring KPCKP and for controlling the spread of this organism.
Quinolone Resistance Mechanisms in Salmonella enterica Serovars Hadar, Kentucky, Virchow, Schwarzengrund, and 4,5,12:i:−, Isolated from Humans in Switzerland, and Identification of a Novel
qnrD
Variant,
qnrD2
, in
S
. Hadar
Authors: Abgottspon Helga , Zurfluh Katrin , Nüesch-Inderbinen Magdalena , Hächler Herbert , Stephan Roger 
Published: April 2014

ABSTRACT

Human isolates of
Salmonella enterica
serovars Hadar, Kentucky, Virchow, Schwarzengrund, and the monophasic variant of
S
. Typhimurium,
Salmonella enterica
subsp.
enterica
serovar 4,5,12:i:− were examined for mutations within the quinolone resistance target genes
gyrA
,
gyrB
,
parC
, and
parE
and for plasmid-mediated resistance genes. Differences were observed among the serovars. A novel variant of
qnrD
,
qnrD2
, was detected in an
S
. Hadar isolate.