bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective eculizumab therapy followed by BMT in a boy with paroxysmal nocturnal hemoglobinuria
Authors: Oshiro Hiroko , Goi Kumiko , Akahane Koshi , Inukai Takeshi , Sugita Kanji 
Published: April 2015

AbstractA 9‐year‐old boy with paroxysmal nocturnal hemoglobinuria/aplastic anemia syndrome (PNH/AA) developed hemolytic crisis after receiving immunosuppressive therapy. Eculizumab dramatically relieved the signs and symptoms and then he safely underwent unrelated bone marrow transplantation, suggesting the feasibility and effectiveness of eculizumab before stem cell transplantation in children with PNH/AA in hemolytic crisis.
Severe intrinsic acute kidney injury associated with therapeutic doses of acetaminophen
Authors: Ito Tatsuya , Watanabe Shojiro , Tsuruga Kazushi , Aizawa Tomomi , Hirono Koji , Ito Etsuro , Joh Kensuke , Tanaka Hiroshi 
Published: April 2015

AbstractAcetaminophen is a commonly used medication to manage fever and pain in children and the drug is generally considered to be safe when used at appropriate therapeutic dosages. Recently, we encountered the case of a 3‐year‐old Japanese girl who suffered from severe intrinsic acute kidney injury (AKI) after therapeutic doses of acetaminophen for a fever due to viral infection. Renal biopsy indicated severe acute tubular necrosis with a significant striped interstitial fibrosis and mild interstitial inflammation. Unfortunately, she developed chronic kidney disease thereafter. This is the youngest case of biopsy‐proven severe intrinsic AKI associated with therapeutic doses of acetaminophen. Acetaminophen, even if administered at therapeutic dosages, may be dangerous in selected children, especially with possible pre‐existing volume depletion.
A Better Appraisal of Wittgenstein's Tractatus Manuscript
Authors: Bazzocchi Luciano 
Published: April 2015

AbstractThis paper substitutes a structural hermeneutics for the sequential approach to the Tractatus and its manuscript, which leaves the manuscript completely unexplained. All the pieces come together only if we recognise that Wittgenstein's book is a hierarchical object that was composed following a top‐down strategy. Therefore, we realise that the “summary on scattered sheets” represents the perspicuous version of the manuscript, the correlations with the Notebooks become obvious and the “supplements” can be reconstructed. A correct dating of the composition allows us to understand how it was possible, without digital technologies except from an ingenious application of the decimal system, to achieve this formal masterpiece.
The dynamics of doping:LanceArmstrong, theUnitedStatesAnti‐DopingAgency and the regulatory governance of professional cycling
Authors: de Bruijn Hans , Groenleer Martijn , van Ruijven Theo 
Published: April 2015

AbstractOn 10October 2012, theUnitedStatesAnti‐DopingAgency published an investigative report on the use of performance‐enhancing drugs by professional cyclistLanceArmstrong. The report paints a disconcerting picture of the doping program that Armstrong and hisUSPostal Service professional cycling team managed to carry out for several years, despite being subject to many inspections. It contains a wealth of unique empirical data, including a large number of affidavits. In this article, we use this data to answer the question of how Armstrong was able to prolong prohibited behavior. In doing so, we focus in particular on the interactions between Armstrong and the many doping inspectors he encountered. Our analysis results in a variety of answers to this question. First, inspectors were confronted with an inspectee who behaved as an “amoral calculator” and acted strategically. The strategies of inspectors were not adequately attuned to such behavior. Second, the team's internal professional control was neutralized by various factors, including its strict hierarchy and the many friendships within the team. And, finally, the environment created strong incentives to start doping and subsequently deny doing so. We argue that the dynamics underlying doping necessitate a combination of measures to regulate the use of performance‐enhancing drugs in the field of professional cycling and beyond.
Bronchial epithelial cells: The key effector cells in the pathogenesis of chronic obstructive pulmonary disease?
Authors: Gao Wei , Li Lingling , Wang Yujie , Zhang Sini , Adcock Ian M , Barnes Peter J. , Huang Mao , Yao Xin 
Published: April 2015

AbstractThe primary function of the bronchial epithelium is to act as a defensive barrier aiding the maintenance of normal airway function. Bronchial epithelial cells (BEC) form the interface between the external environment and the internal milieu, making it a major target of inhaled insults. However, BEC can also serve as effectors to initiate and orchestrate immune and inflammatory responses by releasing chemokines and cytokines, which recruit and activate inflammatory cells. They also produce excess reactive oxygen species as a result of an oxidant/antioxidant imbalance that contributes to chronic pulmonary inflammation and lung tissue damage. Accumulated mucus from hyperplastic BEC obstructs the lumen of small airways, whereas impaired cell repair, squamous metaplasia and increased extracellular matrix deposition underlying the epithelium is associated with airway remodelling particularly fibrosis and thickening of the airway wall. These alterations in small airway structure lead to airflow limitation, which is critical in the clinical diagnosis of chronic obstructive pulmonary disease (COPD). In this review, we discuss the abnormal function of BEC within a disturbed immune homeostatic environment consisting of ongoing inflammation, oxidative stress and small airway obstruction. We provide an overview of recent insights into the function of the bronchial epithelium in the pathogenesis of COPD and how this may provide novel therapeutic approaches for a number of chronic lung diseases.
Estimation of Fibre Length Distributions from Fibre Endpoints
Authors: Kuhlmann Malte , Redenbach Claudia 
Published: April 2015

AbstractEstimating the fibre length distribution in composite materials is of practical relevance in materials science. We propose an estimator for the fibre length distribution using the point process of fibre endpoints as input. Assuming that this point process is a realization of a Neyman–Scott process, we use results for the reduced second moment measure to derive a consistent and unbiased estimator for the fibre length distribution. We introduce various versions of the estimator taking anisotropy or errors in the observation into account. The estimator is evaluated using a heuristic for its mean squared error as well as a simulation study. Finally, the estimator is applied to the fibre endpoint process extracted from a tomographic image of a glass fibre composite.
Generalized Maximum Spacing Estimation for Multivariate Observations
Authors: Kuljus Kristi , Ranneby Bo 
Published: April 2015

AbstractIn this paper, the maximum spacing method is considered for multivariate observations. Nearest neighbour balls are used as a multidimensional analogue to univariate spacings. A class of information‐type measures is used to generalize the concept of maximum spacing estimators. Weak and strong consistency of these generalized maximum spacing estimators are proved both when the assigned model class is correct and when the true density is not a member of the model class. An example of the generalized maximum spacing method in model validation context is discussed.
The Intertwined Relationship between Self‐esteem and Peer Stress Among Korean Adolescents: A Prospective Longitudinal Study
Authors: Yu Jeong Jin 
Published: April 2015

AbstractAlthough the association between self‐esteem and peer stress among adolescents is not unidirectional, and the two constructs probably coevolve and coexist over time, these two constructs and their possible mutual influence have rarely been tested in one single study. The present study examined whether there are bidirectional interactions between self‐esteem and perceptions of peer stress across five or six annual waves using a nationally representative sample of two cohorts of South Korean youth. The sample comprised 2844 fourth graders (M = 9.86 years) and 3449 eighth graders (M = 13.79 years) at wave 1. Findings suggested that self‐esteem was positively associated with peer stress in early and middle adolescence, whereas peer stress was negatively associated with self‐esteem in early adolescence, but had positive links in middle and late adolescence. The implications of the results were discussed.
Learning Patient Safety in Academic Settings: A Comparative Study of Finnish and British Nursing Students’ Perceptions
Authors: Tella Susanna , Smith Nancy‐Jane , Partanen Pirjo , Turunen Hannele 
Published: April 2015

ABSTRACTBackgroundGlobalization of health care demands nursing education programs that equip students with evidence‐based patient safety competences in the global context. Nursing students’ entrance into clinical placements requires professional readiness. Thus, evidence‐based learning activities about patient safety must be provided in academic settings prior to students’ clinical placements.AimsTo explore and compare Finnish and British nursing students’ perceptions of learning about patient safety in academic settings to inform nursing educators about designing future education curriculum.MethodsA purpose‐designed instrument, Patient Safety in Nursing Education Questionnaire (PaSNEQ) was used to examine the perceptions of Finnish (n = 195) and British (n = 158) nursing students prior to their final year of registration. Data were collected in two Finnish and two English nursing schools in 2012. Logistic regressions were used to analyze the differences.ResultsBritish students reported more inclusion (p < .001) of “gaining knowledge,” “training skills,” and “highlighting affirmative attitudes and motivation” related to patient safety in their programs. Both student groups considered patient safety education to be more valuable for their own learning than what their programs had provided. Training patient safety skills in the academic settings were the strongest predictors for differences (odds ratio [OR] = 34.69, 95% confidence interval [CI] 7.39–162.83), along with work experience in the healthcare sector (OR = 3.02, 95% CI 1.39–6.58).Linking Evidence to ActionTo prepare nursing students for practical work, training related to clear communication, reporting errors, systems‐based approaches, interprofessional teamwork, and use of simulation in academic settings requires comprehensive attention, especially in Finland. Overall, designing patient safety‐affirming nursing curricula in collaboration with students may enhance their positive experiences on teaching and learning about patient safety. An international collaboration between educators could help to develop and harmonize patient safety education and to better prepare nurses for practice in the global context.
Alternating Sitting and Standing Increases the Workplace Energy Expenditure of Overweight Adults
Authors: Thorp Alicia Ann , Kingwell Bronwyn A. , English Coralie , Hammond Louise , Sethi Parneet , Owen Neville , Dunstan David W. 
Published: April 2015

Background:To determine whether alternating bouts of sitting and standing at work influences daily workplace energy expenditure (EE).Methods:Twenty-three overweight/obese office workers (mean ± SD; age: 48.2 ± 7.9 y, body mass index: 29.6 ± 4.0 kg/m2) undertook two 5-day experimental conditions in an equal, randomized order. Participants wore a “metabolic armband” (SenseWear Armband Mini) to estimate daily workplace EE (KJ/8 h) while working (1) in a seated work posture (SIT condition) or (2) alternating between a standing and seated work posture every 30 minutes using a sit-stand workstation (STAND-SIT condition). To assess the validity of the metabolic armband, a criterion measure of acute EE (KJ/min; indirect calorimetry) was performed on day 4 of each condition.Results:Standing to work acutely increased EE by 0.7 [95% CI 0.3–1.0] KJ/min (13%), relative to sitting (P = .002). Compared with indirect calorimetry, the metabolic armband provided a valid estimate of EE while standing to work (mean bias: 0.1 [–0.3 to 0.4] KJ/min) but modestly overestimated EE while sitting (P = .005). Daily workplace EE was greatest during the STAND-SIT condition (mean condition difference [95% CI]: 76 [8–144] KJ/8-h workday, P = .03).Conclusions:Intermittent standing at work can modestly increase daily workplace EE compared with seated work in overweight/obese office workers.
MIV-150/Zinc Acetate Gel Inhibits Cell-Associated Simian-Human Immunodeficiency Virus Reverse Transcriptase Infection in a Macaque Vaginal Explant Model
Authors: Barnable Patrick , Calenda Giulia , Bonnaire Thierry , Menon Radhika , Levendosky Keith , Gettie Agegnehu , Blanchard James , Cooney Michael L. , Fernández-Romero José A. , Zydowsky Thomas M. , Teleshova Natalia 
Published: April 2015

ABSTRACT

The transmission of both cell-free and cell-associated immunodeficiency viruses has been demonstrated directly in multiple animal species and possibly occurs in humans, as suggested by genotyping of the infecting human immunodeficiency virus (HIV) in acutely infected women and in semen from their partners. Therefore, a microbicide may need to block both mechanisms of HIV transmission to achieve maximum efficacy. To date, most of the preclinical evaluation of candidate microbicides has been performed using cell-free HIV. New models of mucosal transmission of cell-associated HIV are needed to evaluate candidate microbicide performance. The MIV-150/zinc acetate/carrageenan (MZC) gel protects Depo-Provera-treated macaques against cell-free simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection when applied vaginally up to 8 h before challenge. We recently demonstrated the potent activity of MZC gel against cell-free SHIV-RT in macaque vaginal explants. In the current study, we established a cell-associated SHIV-RT infection model of macaque vaginal tissues and tested the activity of MZC gel in this model. MZC gel protected tissues against cell-associated SHIV-RT infection when present at the time of viral exposure or when applied up to 4 days prior to viral challenge. These data support clinical testing of the MZC gel. Overall, our
ex vivo
model of cell-associated SHIV-RT infection in macaque vaginal mucosa complements the cell-free infection models, providing tools for prioritization of products that block both modes of HIV transmission.
Molecular Characterization of IS
CR1
-Mediated
bla
PER-1
in a Non-O1, Non-O139 Vibrio cholerae Strain from China
Authors: Wu Jun , Xie Lianyan , Zhang Fangfang , Ni Yuxing , Sun Jingyong 
Published: April 2015

ABSTRACT

We report the detection of PER-1 extended-spectrum β-lactamase (ESBL) in a clinical non-O1, non-O139
Vibrio cholerae
strain from China. IS
CR1
-mediated
bla
PER-1
was embedded in a complex In
4
family class 1 integron belonging to the lineage of Tn
1696
on a conjugative IncA/C plasmid. A free 8.98-kb circular molecule present with the IS
CR1-bla
PER-1
–truncated 3′-conserved sequence (CS) structure was detected in this isolate. These findings may provide insight into the mobilization of
bla
PER-1
.
Limited Sampling Strategy and Target Attainment Analysis for Levofloxacin in Patients with Tuberculosis
Authors: Alsultan Abdullah , An Guohua , Peloquin Charles A. 
Published: April 2015

ABSTRACT

There is an urgent need to improve and shorten the treatment of tuberculosis (TB) and multidrug resistant tuberculosis (MDR-TB). Levofloxacin, a newer fluoroquinolone, has potent activity against TB both
in vitro
and
in vivo
. Levofloxacin dosing can be optimized to improve the treatment of both TB and MDR-TB. Levofloxacin efficacy is linked primarily to the ratio of the area under the concentration-time curve for the free fraction of drug (
f
AUC) to the MIC. Since obtaining a full-time concentration profile is not feasible in the clinic, we developed a limited sampling strategy (LSS) to estimate the AUC. We also utilized Monte Carlo simulations to evaluate the dosing of levofloxacin. Pharmacokinetic data were obtained from 10 Brazilian TB patients. The pharmacokinetic data were fitted with a one-compartment model. LSSs were developed using two methods: linear regression and Bayesian approaches. Several LSSs predicted levofloxacin AUC with good accuracy and precision. The most accurate were the method using two samples collected at 4 and 6 h (
R
2
= 0.91 using linear regression and 0.97 using Bayesian approaches) and that using samples collected at 2 and 6 h (
R
2
= 0.90 using linear regression and 0.96 using Bayesian approaches). The 2-and-6-h approach also provides a good estimate of the maximum concentration of the drug in serum (
C
max
). Our target attainment analysis showed that higher doses (17 to 20 mg/kg of body weight) of levofloxacin might be needed to improve its activity. Doses in the range of 17 to 20 mg/kg showed good target attainment for MICs from 0.25 to 0.50. At an MIC of 2, poor target attainment was observed across all doses. This LSS for levofloxacin can be used for therapeutic drug monitoring and for future pharmacokinetic/pharmacodynamic studies.
Pharmacokinetic Determinants of Virological Response to Raltegravir in the
In Vitro
Pharmacodynamic Hollow-Fiber Infection Model System
Authors: Brown Ashley N. , Adams Jonathan R. , Baluya Dodge L. , Drusano George L. 
Published: April 2015

ABSTRACT

Daily administration (q24h) of raltegravir has been shown to be as efficacious as twice-daily administration (q12h) in the hollow-fiber infection model (HFIM) system. However, q24h regimens were not noninferior to q12h dosing in a clinical trial. We hypothesized that between-patient variability in raltegravir pharmacokinetics (PK) was responsible for the discordance in conclusions between the
in vitro
and
in vivo
studies. Hollow-fiber cartridges were inoculated with HIV-infected H9 cells and uninfected CEM-SS cells. Four cartridges received the total daily exposure (800 mg) q24h and four received half the daily exposure (400 mg) q12h. PK profiles with half-lives of 8, 4, 3, and 2 h were simulated for each dosing interval. Cell-to-cell viral spread was assessed by flow cytometry. Viral inhibition was similar between q24h and q12h dosing at the 8- and 4-h half-lives. The q24h dosing was not as efficacious as the q12h dosing when faster half-lives were simulated; a lack of viral suppression was observed at days 3 and 4 for the 2- and 3-h half-lives, respectively. The discrepancy in conclusions between the
in vitro
HFIM system studies and clinical trials is likely due to the large interindividual variation in raltegravir PK.
Factors Associated with Antibiotic Misuse in Outpatient Treatment for Upper Respiratory Tract Infections
Authors: Schroeck Jennifer L. , Ruh Christine A. , Sellick John A. , Ott Michael C. , Mattappallil Arun , Mergenhagen Kari A. 
Published: April 2015

ABSTRACT
The Centers for Disease Control and Prevention has promoted the appropriate use of antibiotics since 1995 when it initiated the National Campaign for Appropriate Antibiotic Use in the Community. This study examined upper respiratory tract infections included in the campaign to determine the degree to which antibiotics were appropriately prescribed and subsequent admission rates in a veteran population. This study was a retrospective chart review conducted among outpatients with a diagnosis of a respiratory tract infection, including bronchitis, pharyngitis, sinusitis, or nonspecific upper respiratory tract infection, between January 2009 and December 2011. The study found that 595 (35.8%) patients were treated appropriately, and 1,067 (64.2%) patients received therapy considered inappropriate based on the Get Smart Campaign criteria. Overall the subsequent readmission rate was 1.5%. The majority (77.5%) of patients were prescribed an antibiotic. The most common antibiotics prescribed were azithromycin (39.0%), amoxicillin-clavulanate (13.2%), and moxifloxacin (7.5%). A multivariate regression analysis demonstrated significant predictors of appropriate treatment, including the presence of tonsillar exudates (odds ratio [OR], 0.6; confidence interval [CI], 0.3 to 0.9), fever (OR, 0.6; CI, 0.4 to 0.9), and lymphadenopathy (OR, 0.4; CI, 0.3 to 0.6), while penicillin allergy (OR, 2.9; CI, 1.7 to 4.7) and cough (OR, 1.6; CI, 1.1 to 2.2) were significant predictors for inappropriate treatment. Poor compliance with the Get Smart Campaign was found in outpatients for respiratory infections. Results from this study demonstrate the overprescribing of antibiotics, while providing a focused view of improper prescribing. This article provides evidence that current efforts are insufficient for curtailing inappropriate antibiotic use.
MAPK1 of Leishmania donovani Modulates Antimony Susceptibility by Downregulating P-Glycoprotein Efflux Pumps
Authors: Garg Mansi , Goyal Neena 
Published: April 2015

ABSTRACT

Emergence of resistance to pentavalent antimonials has become a severe obstacle in the treatment of visceral leishmaniasis (VL) in the Indian subcontinent. Mitogen-activated protein kinases (MAPKs) are well-known mediators of signal transduction of eukaryotes, regulating important processes, like proliferation, differentiation, stress response, and apoptosis. In
Leishmania
, MAPK1 has been shown to be consistently downregulated in antimony-resistant field isolates, suggesting that it has a role in antimony resistance. The present work investigates the molecular mechanism of MAPK1 in antimony resistance in
Leishmania donovani
. The
L. donovani
MAPK1 (LdMAPK1) single-allele replacement mutants exhibited increased resistance to Sb(III) (5.57-fold) compared to wild-type promastigotes, while overexpressing parasites became much more susceptible to antimony. The LdMAPK1-mediated drug sensitivity was directly related to antimony-induced apoptotic death of the parasite, as was evidenced by a 4- to 5-fold decrease in cell death parameters in deletion mutants and a 2- to 3-fold increase in MAPK1-overexpressing cells. LdMAPK1-underexpressing parasites also exhibited increased P-glycoprotein (P-gp)-mediated efflux pump activity, while a significant decrease in pump activity was observed in overexpressing cells. This change in efflux pump activity was directly related to expression levels of P-gp in all cell lines. However, episomal complementation of the gene restored normal growth, drug sensitivity, P-gp expression, and efflux pump activity. The data indicate that LdMAPK1 negatively regulates the expression of P-glycoprotein-type efflux pumps in the parasite. The decrease in efflux pump activity with an increase in LdMAPK1 expression may result in increased antimony accumulation in the parasite, making it more vulnerable to the drug.