bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Routine Electrocardiography Necessary Before Initiation of Propranolol for Treatment of Infantile Hemangiomas?
Authors: Yarbrough Kevin B. , Tollefson Megha M. , Krol Alfons L. , Leitenberger Sabra L. , Mann Julianne A. , MacArthur Carol J. 
Published: September 2016

AbstractBackgroundIn recent years propranolol has become the treatment of choice for infantile hemangiomas (IHs). There is broad variation in the approach to propranolol initiation in clinical practice. This retrospective study explored the effectiveness of routine pre‐treatment ECG in screening infants being considered for systemic treatment with propranolol.MethodsAll patients seen in the outpatient pediatric dermatology clinics at Oregon Health and Sciences University (OHSU) and The Mayo Clinic Rochester (MCR), as well as those seen in multidisciplinary vascular anomalies clinics, who had ECGs obtained prior to planned initiation of propranolol for treatment of IH from 2008 to 2013, were identified. A total of 162 patients were included in the study.ResultsWe found that 43% (69) of routine ECGs were read as abnormal, leading to 28 formal consultation appointments with pediatric cardiologists. After either formal consultation or informal discussion with cardiology, no patients with initially “abnormal” ECGs were ultimately excluded from treatment with propranolol based on routine ECG findings. Additionally no patients in our cohort experienced an adverse effect during treatment that could have been predicted or prevented by ECG prior to initiation of the propranolol.ConclusionOur findings suggest that routine ECG may not be necessary or helpful in the vast majority of patients treated with propranolol for IHs.
The Spreading of Innovation: State Adoptions of Energy and Climate Change Policy
Authors: Bromley‐Trujillo Rebecca , Butler J. S. , Poe John , Davis Whitney 
Published: September 2016

AbstractThe American states are engaged in a variety of policy efforts to mitigate climate change and alter energy usage. While a number of studies have considered the reasons for adoption of renewable energy and climate change policies, they typically consider only one policy in isolation. This study examines policy adoption of 14 energy and climate change programs in a pooled event history analysis. Our primary research questions consider average effects of horizontal policy diffusion, while also identifying factors that vary across policy type. We offer a method of testing whether predictors vary across policies and use this test to incorporate interactions by policy in the statistical analysis. Our results indicate that many of the primary drivers of adoption are political in nature, including state ideology, environmental interest group membership, and diffusion via ideologically similar neighbors. In addition, we find that given policy heterogeneity, a number of determinants vary by policy type, though differences are in magnitude rather than direction.
Likelihood Inference for Multivariate Extreme Value Distributions Whose Spectral Vectors have known Conditional Distributions
Authors: Bienvenüe Alexis , Robert Christian Y. 
Published: September 2016

AbstractMultivariate extreme value statistical analysis is concerned with observations on several variables which are thought to possess some degree of tail dependence. The main approaches to inference for multivariate extremes consist in approximating either the distribution of block component‐wise maxima or the distribution of the exceedances over a high threshold. Although the expressions of the asymptotic density functions of these distributions may be characterized, they cannot be computed in general. In this paper, we study the case where the spectral random vector of the multivariate max‐stable distribution has known conditional distributions. The asymptotic density functions of the multivariate extreme value distributions may then be written through univariate integrals that are easily computed or simulated. The asymptotic properties of two likelihood estimators are presented, and the utility of the method is examined via simulation.
Hobbes on the Order of Sciences: A Partial Defense of the Mathematization Thesis
Authors: Biener Zvi 
Published: September 2016

AbstractAccounts of Hobbes's “system” of sciences oscillate between two extremes. On one extreme, the system is portrayed as wholly axiomatic‐deductive, with statecraft being deduced in an unbroken chain from the principles of logic and first philosophy. On the other, it is portrayed as rife with conceptual cracks and fissures, with Hobbes's statements about its deductive structure amounting to mere window‐dressing. This paper argues that a middle way is found by conceiving of Hobbes's Elements of Philosophy on the model of a mixed‐mathematical science, not the model provided by Euclid's Elements of Geometry. I suggest that Hobbes is a test case for understanding early‐modern system construction more generally, as inspired by the structure of the applied mathematical sciences. This approach has the additional virtue of bolstering in a novel way the thesis that the transformation of philosophy in the long seventeenth century was indebted to mathematics, a thesis that has come under increasing scrutiny in recent years.
Exploitation and Friendship
Authors: Valdman Mikhail 
Published: September 2016

AbstractI argue that Alan Wertheimer's account of unfair advantage‐taking, though flawed, is more plausible than his critics believe. Indeed, I argue that his proposed model for assessing fair exchange—the friendship model—according to which a transaction's terms are unfair to the extent that they deviate from the terms upon which we would expect good friends to transact—is compelling and can serve as the basis for a plausible theory of wrongful exploitation. Wertheimer, I will argue, was wrong to think that friends would transact at “hypothetical market prices.” But he was right to think that friendship norms can provide a plausible account of fair exchange. In this paper, I develop a friendship‐based account of wrongful exploitation, and I argue that it has important advantages over rival theories.
Exploited: Exploitation As A Subjective Category
Authors: Deranty Jean‐Philippe 
Published: September 2016

AbstractI focus on exploitation from the point of view of those who suffer from it, and so I take exploitation as a category of subjective experience. Adopting a subjective perspective on exploitation highlights important conceptual aspects about it and suggests important methodological rules on how to critically discuss social forms of exploitation. I start by introducing some key conceptual distinctions in the first two sections. These distinctions lead me to formulate a first, general definition of exploitation as a subjective category, in the third section of the paper. In the fourth section, I ask what relationship there is between the objective and subjective senses of exploitation, and I turn to the work of Marx. This is because, as I try to argue, Marx's approach is exemplary for tying together an objective and a subjective sense of exploitation. Based on a schematic rendition of Marx's use of a dual perspective on exploitation, in the last sections of the paper, I draw a number of conceptual and normative conclusions.
Role of mTOR inhibitors for the control of viral infection in solid organ transplant recipients
Authors: Pascual Julio , Royuela Ana , Fernández Ana M. , Herrero Ignacio , Delgado Juan F. , Solé Amparo , Guirado Lluis , Serrano Trinidad , de la Torre‐Cisneros Julián , Moreno Asunción , Cordero Elisa , Gallego Roberto , Lumbreras Carlos , Aguado José M. ,   the Spanish Society of Transplantation Virological and Immune Response Investigation Study Group
Published: September 2016

AbstractAppropriate post‐transplant immunosuppressive regimens that avoid acute rejection, while reducing risk of viral reactivation, have been sought, but remain a chimera. Recent evidence suggesting potential regulatory and antiviral effects of mammalian target of rapamycin inhibitors (mTORi) is of great interest. Although the concept of an immunosuppressive drug with antiviral properties is not new, little effort has been made to put the evidence together to assess the management of immunosuppressive therapy in the presence of a viral infection. This review was developed to gather the evidence on antiviral activity of the mTORi against the viruses that most commonly reactivate in adult solid organ recipients: cytomegalovirus (CMV), polyomavirus, Epstein‐Barr virus (EBV), human herpesvirus 8 (HHV8), and hepatitis C virus (HCV). A rapid review methodology and evaluation of quality and consistency of evidence based on the GRADE system was used. The existing literature was variable in nature, although indicating a potential advantage of mTORi in CMV, polyomavirus, and HHV8 infection, and a most doubtful relation with EBV and HCV infection. Several recommendations about the management of these infections are presented that can change certain current patterns of immunosuppression and help to improve the prognosis of the direct and indirect effects of viral infection in solid organ recipients.
Cryptococcal osteomyelitis of the skull in a liver transplant patient
Authors: Pudipeddi Aviv V. , Liu Ken , Watson Geoffrey F. , Davis Rebecca J. , Strasser Simone I. 
Published: September 2016

AbstractCryptococcus neoformans is an opportunistic fungal pathogen and an important cause of morbidity and mortality in immunocompromised patients. We report a case of osteomyelitis caused by C. neoformans in a liver transplant recipient who presented with a headache and scalp lump after sustaining mild head trauma. There was no evidence of central nervous system involvement or dissemination. This is the first known case report of isolated cryptococcal osteomyelitis in a liver transplant recipient.
Ferric carboxymaltose reduces the number of red blood cell units transfused and allows transfusion independence to be obtained in patients with iron deficiency anemia secondary to gastrointestinal chronic blood loss
Authors: Salvadori Ugo , Sandri Marco , Melli Cristina , Polese Francesca , Simeoni Maria , Capelli Stefano , Al‐Khaffaf Ahmad 
Published: September 2016

BACKGROUNDThe aim of this study was to evaluate the effectiveness of ferric carboxymaltose (FCM) in patients with iron deficiency anemia (IDA) secondary to gastrointestinal chronic blood loss (CBL), who received chronic transfusion support.STUDY DESIGN AND METHODSWe retrospectively evaluated 38 patients with IDA (hemoglobin [Hb] < 10 g/dL and ferritin < 12 ng/mL or transferrin saturation [TSAT] < 16%) refractory or intolerant to oral iron therapy that necessitated transfusion support in the previous 12 months. They were treated with FCM (500‐2500 mg). The primary endpoint was to evaluate the reduction of transfusion requirements (red blood cell [RBC] units) after FCM treatment.RESULTSThe median age of the cohort was 78 years, with a male:female ratio of 22:16. Before FCM treatment a median of 6 RBC units had been transfused. At the treatment (T0) the median value of Hb was 8.7 g/dL, the TSAT 6%, and ferritin 12 ng/mL. The median FCM dose was 1000 mg. At 5 weeks from T0 the median Hb level was 11 g/dL, with a median increase of 2.4 g/dL. With a median follow‐up of 326 days, the median transfusion requirement was 0 RBC units, significantly lower than before T0 (p < 0.001). Overall 17 patients still necessitated transfusion support. Twenty‐three patients needed retreatment with FCM for recurrence of IDA: 10 of them obtained a response again. The percentage of transfusion‐independent patients at median follow‐up was equal to 52%.CONCLUSIONIn patients with IDA secondary to CBL, FCM significantly reduces the need of transfusions and achieves transfusion independence in half of the cases.
The SHP2‐ERK2 signaling pathway regulates branched I antigen formation by controlling the binding of CCAAT/enhancer binding protein α to the IGnTC promoter region during erythroid differentiation
Authors: Liao Yi‐Jen , Lee Yen‐Hua , Chang Fu‐Ling , Ho Hsun , Huang Chin‐Han , Twu Yuh‐Ching 
Published: September 2016

BACKGROUNDPhosphorylation status of the transcription factor CCAAT/enhancer binding protein α (C/EBPα) has been demonstrated in a human hematopoietic cell model to regulate the formation of branched I antigen by affecting its binding affinity to the promoter region of the IGnTC gene during erythroid and granulocytic differentiation.STUDY DESIGN AND METHODSThe K‐562 cell line was induced to differentiate into red blood cells (RBCs) or granulocytes by sodium butyrate or retinoic acid, respectively, to study the involvement of three MAP kinase pathways in I antigen synthesis. The regulatory effects of the extracellular signal‐regulated kinase (ERK)2‐Src homology region 2 domain‐containing phosphatase 2 (SHP2) pathway on phosphorylation status and binding affinities of C/EBPα as well as the subsequent activation of IGnTC and synthesis of surface I formation were studied in wild‐type K‐562 cells and in mutant cells that overexpress ERK2 and SHP2.RESULTSWe found that SHP2‐ERK2 signaling regulates the phosphorylation status of C/EBPα to alter its binding affinity onto the IGnTC promoter region, thereby activating the synthesis of cell surface I antigen formation during erythropoiesis.CONCLUSIONSHP2‐ERK2 signaling acts upstream of C/EBPα as a regulator of cell surface I antigen synthesis. Such regulation is specific for RBC but not for granulocyte differentiation.
The Development of Drugs against Acanthamoeba Infections
Authors: Siddiqui Ruqaiyyah , Aqeel Yousuf , Khan Naveed Ahmed 
Published: September 2016

ABSTRACT

For the past several decades, there has been little improvement in the morbidity and mortality associated with
Acanthamoeba
keratitis and
Acanthamoeba
encephalitis, respectively. The discovery of a plethora of antiacanthamoebic compounds has not yielded effective marketed chemotherapeutics. The rate of development of novel antiacanthamoebic chemotherapies of translational value and the lack of interest of the pharmaceutical industry in developing such chemotherapies have been disappointing. On the other hand, the market for contact lenses/contact lens disinfectants is a multi-billion-dollar industry and has been successful and profitable. A better understanding of drugs, their targets, and mechanisms of action will facilitate the development of more-effective chemotherapies. Here, we review the progress toward phenotypic drug discovery, emphasizing the shortcomings of useable therapies.
Comparative Evaluation of the Predictive Performances of Three Different Structural Population Pharmacokinetic Models To Predict Future Voriconazole Concentrations
Authors: Farkas Andras , Daroczi Gergely , Villasurda Phillip , Dolton Michael , Nakagaki Midori , Roberts Jason A. 
Published: September 2016

ABSTRACT

Bayesian methods for voriconazole therapeutic drug monitoring (TDM) have been reported previously, but there are only sparse reports comparing the accuracy and precision of predictions of published models. Furthermore, the comparative accuracy of linear, mixed linear and nonlinear, or entirely nonlinear models may be of high clinical relevance. In this study, models were coded into individually designed optimum dosing strategies (ID-ODS) with voriconazole concentration data analyzed using inverse Bayesian modeling. The data used were from two independent data sets, patients with proven or suspected invasive fungal infections (
n =
57) and hematopoietic stem cell transplant recipients (
n =
10). Observed voriconazole concentrations were predicted whereby for each concentration value, the data available to that point were used to predict that value. The mean prediction error (ME) and mean squared prediction error (MSE) and their 95% confidence intervals (95% CI) were calculated to measure absolute bias and precision, while ΔME and ΔMSE and their 95% CI were used to measure relative bias and precision, respectively. A total of 519 voriconazole concentrations were analyzed using three models. MEs (95% CI) were 0.09 (−0.02, 0.22), 0.23 (0.04, 0.42), and 0.35 (0.16 to 0.54) while the MSEs (95% CI) were 2.1 (1.03, 3.17), 4.98 (0.90, 9.06), and 4.97 (−0.54 to 10.48) for the linear, mixed, and nonlinear models, respectively. In conclusion, while simulations with the linear model were found to be slightly more accurate and similarly precise, the small difference in accuracy is likely negligible from the clinical point of view, making all three approaches appropriate for use in a voriconazole TDM program.
Molecular Epidemiology and Genome Dynamics of New Delhi Metallo-β-Lactamase-Producing Extraintestinal Pathogenic Escherichia coli Strains from India
Authors: Ranjan Amit , Shaik Sabiha , Mondal Agnismita , Nandanwar Nishant , Hussain Arif , Semmler Torsten , Kumar Narender , Tiwari Sumeet K. , Jadhav Savita , Wieler Lothar H. , Ahmed Niyaz 
Published: September 2016

ABSTRACT

The global dissemination and increasing incidence of carbapenem-resistant, Gram-negative organisms have resulted in acute public health concerns. Here, we present a retrospective multicenter study on molecular characterization of metallo-β-lactamase (MBL)-producing clinical
Escherichia coli
isolates recovered from extraintestinal infections in two hospitals in Pune, India. We screened a large sample size of 510
E. coli
isolates for MBL production wherein we profiled their molecular determinants, antimicrobial resistance phenotypes, functional virulence properties, genomic features, and transmission dynamics. Approximately 8% of these isolates were MBL producers, the majority of which were of the NDM-1 (69%) type, followed by NDM-5 (19%), NDM-4 (5.5%), and NDM-7 (5.5%). MBL producers were resistant to all antibiotics tested except for colistin, fosfomycin, and chloramphenicol, which were effective to various extents. Plasmids were found to be an effective means of dissemination of NDM genes and other resistance traits. All MBL producers adhered to and invaded bladder epithelial (T24) cells and demonstrated significant serum resistance. Genomic analysis of MBL-producing
E. coli
isolates revealed higher resistance but a moderate virulence gene repertoire. A subset of NDM-1-positive
E. coli
isolates was identified as dominant sequence type 101 (ST101) while two strains belonging to ST167 and ST405 harbored NDM-5. A majority of MBL-producing
E. coli
strains revealed unique genotypes, suggesting that they were clonally unrelated. Overall, the coexistence of virulence and carbapenem resistance in clinical
E. coli
isolates is of serious concern. Moreover, the emergence of NDM-1 among the globally dominant
E. coli
ST101 isolates warrants stringent surveillance and control measures.
Ceftriaxone-Resistant Neisseria gonorrhoeae Isolates (2010 to 2014) in France Characterized by Using Whole-Genome Sequencing
Authors: de Curraize Claire , Kumanski Sylvain , Micaëlo Maïté , Fournet Nelly , La Ruche Guy , Meunier Fabienne , Amarsy Rishma , Jacquier Hervé , Cambau Emmanuelle , Goubard Agathe , Bercot Béatrice 
Published: September 2016

ABSTRACT

Two extended-spectrum cephalosporin-resistant
Neisseria gonorrhoeae
isolates were discovered among 6,340 (0.03%) French isolates between 2010 and 2014. One isolate corresponded to the F89 multidrug-resistant
N. gonorrhoeae
isolate harboring a
penA
mosaic; whole-genome sequencing highlighted an additional R251H substitution in the
ftsX
gene recently involved in cephalosporin resistance. The other, ceftriaxone-resistant isolate (MIC, 0.25 mg/liter) harbored the PBP2 pattern XXXVI plus a P551S substitution and belonged to sequence type ST1579 (multilocus sequence typing [MLST]).
Conserved Arginines at the P-Protein Stalk Binding Site and the Active Site Are Critical for Ribosome Interactions of Shiga Toxins but Do Not Contribute to Differences in the Affinity of the A1 Subunits for the Ribosome
Authors: Basu Debaleena , Kahn Jennifer N. , Li Xiao-Ping , Tumer Nilgun E. 
Published: September 2016

ABSTRACT
The A1 subunits of Shiga toxin 1 (Stx1A1) and Shiga toxin 2 (Stx2A1) interact with the conserved C termini of ribosomal-stalk P-proteins to remove a specific adenine from the sarcin/ricin loop. We previously showed that Stx2A1 has higher affinity for the ribosome and higher catalytic activity than Stx1A1. To determine if conserved arginines at the distal face of the active site contribute to the higher affinity of Stx2A1 for the ribosome, we mutated Arg172, Arg176, and Arg179 in both toxins. We show that Arg172 and Arg176 are more important than Arg179 for the depurination activity and toxicity of Stx1A1 and Stx2A1. Mutation of a single arginine reduced the depurination activity of Stx1A1 more than that of Stx2A1. In contrast, mutation of at least two arginines was necessary to reduce depurination by Stx2A1 to a level similar to that of Stx1A1. R176A and R172A/R176A mutations eliminated interaction of Stx1A1 and Stx2A1 with ribosomes and with the stalk, while mutation of Arg170 at the active site reduced the binding affinity of Stx1A1 and Stx2A1 for the ribosome, but not for the stalk. These results demonstrate that conserved arginines at the distal face of the active site are critical for interactions of Stx1A1 and Stx2A1 with the stalk, while a conserved arginine at the active site is critical for non-stalk-specific interactions with the ribosome. Arginine mutations at either site reduced ribosome interactions of Stx1A1 and Stx2A1 similarly, indicating that conserved arginines are critical for ribosome interactions but do not contribute to the higher affinity of Stx2A1 for the ribosome.
Gamma Interferon Is Required for Optimal Antibody-Mediated Immunity against Genital Chlamydia Infection
Authors: Naglak Elizabeth K. , Morrison Sandra G. , Morrison Richard P. 
Published: September 2016

ABSTRACTDefining the mechanisms of immunity conferred by the combination of antibody and CD4+T cells is fundamental to designing an efficacious chlamydial vaccine. Using theChlamydia muridarumgenital infection model of mice, which replicates many features of humanC. trachomatisinfection and avoids the characteristic low virulence ofC. trachomatisin the mouse, we previously demonstrated a significant role for antibody in immunity to chlamydial infection. We found that antibody alone was not protective. Instead, protection appeared to be conferred through an undefined antibody-cell interaction. Using gene knockout mice andin vivocellular depletion methods, our data suggest that antibody-mediated protection is dependent on the activation of an effector cell population in genital tract tissues by CD4+T cells. Furthermore, the CD4+T cell-secreted cytokine gamma interferon (IFN-γ) was found to be a key component of the protective antibody response. The protective function of IFN-γ was not related to the immunoglobulin class or to the magnitude of theChlamydia-specific antibody response or to recruitment of an effector cell population to genital tract tissue. Rather, IFN-γ appears to be necessary for activation of the effector cell population that functions in antibody-mediated chlamydial immunity. Our results confirm the central role of antibody in immunity to chlamydia reinfection and demonstrate a key function for IFN-γ in antibody-mediated protection.