bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease
Authors: Zhao Wei , Zhang Daolun , Fakhoury May , Fahd Mony , Duquesne Frédérique , Storme Thomas , Baruchel André , Jacqz-Aigrain Evelyne 
Published: March 2014

ABSTRACT

An increase in vancomycin dose has been proposed in adults with malignant hematological disease. As pediatric data are limited, our aim was to evaluate the population pharmacokinetics of vancomycin in order to define the appropriate dosing regimen in children with malignant hematological disease. Vancomycin concentrations were collected prospectively during therapeutic monitoring. Population pharmacokinetic analysis was performed using NONMEM software. Seventy children (age range, 0.3 to 17.7 years) were included. With the current recommended dosing regimen of 40 to 60 mg/kg/day, 53 children (76%) had subtherapeutic steady-state trough concentrations (
C
ss/min
of <10 mg/liter). A one-compartment model with first-order elimination was developed. Systematic covariate analysis identified that weight significantly influenced clearance (CL) and volume of distribution (
V
) with power functions of 0.677 for CL and 0.838 for
V
. Vancomycin CL also significantly increased with increases in creatinine clearance and seemed to be higher in children with malignant hematological disease than in the general pediatric population. The model was validated internally. Its predictive performance was further confirmed in an external validation by Bayesian estimation. A patient-tailored dosing regimen was developed based on the final pharmacokinetic model and showed that a higher proportion of patients reached the target
C
ss/min
than with the traditional mg/kg-basis dose (60% versus 49%) and that the risks associated with underdosing or overdosing were reduced. This is the first population pharmacokinetic study of vancomycin in children with malignant hematological disease. An optimized dosing regimen, taking into account patient weight, creatinine clearance, and susceptibility of the pathogens involved, could routinely be used to individualize vancomycin therapy in this vulnerable population.
Interleukin 17A Promotes Pneumococcal Clearance by Recruiting Neutrophils and Inducing Apoptosis through a p38 Mitogen-Activated Protein Kinase-Dependent Mechanism in Acute Otitis Media
Authors: Wang Wei , Zhou Aie , Zhang Xuemei , Xiang Yun , Huang Yifei , Wang Lei , Zhang Shuai , Liu Yusi , Yin Yibing , He Yujuan 
Published: March 2014

ABSTRACT

Streptococcus pneumoniae
is a Gram-positive and human-restricted pathogen colonizing the nasopharynx with an absence of clinical symptoms as well as a major pathogen causing otitis media (OM), one of the most common childhood infections. Upon bacterial infection, neutrophils are rapidly activated and recruited to the infected site, acting as the frontline defender against emerging microbial pathogens via different ways. Evidence shows that interleukin 17A (IL-17A), a neutrophil-inducing factor, plays important roles in the immune responses in several diseases. However, its function in response to
S. pneumoniae
OM remains unclear. In this study, the function of IL-17A in response to
S. pneumoniae
OM was examined using an
in vivo
model. We developed a model of acute OM (AOM) in C57BL/6 mice and found that neutrophils were the dominant immune cells that infiltrated to the middle ear cavity (MEC) and contributed to bacterial clearance. Using IL-17A knockout (KO) mice, we found that IL-17A boosted neutrophil recruitment to the MEC and afterwards induced apoptosis, which was identified to be conducive to bacterial clearance. In addition, our observation suggested that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was involved in the recruitment and apoptosis of neutrophils mediated by IL-17A. These data support the conclusion that IL-17A contributes to the host immune response against
S. pneumoniae
by promoting neutrophil recruitment and apoptosis through the p38 MAPK signaling pathway.
Early Changes by
18
Fluorodeoxyglucose Positron Emission Tomography Coregistered with Computed Tomography Predict Outcome after Mycobacterium tuberculosis Infection in Cynomolgus Macaques
Authors: Coleman M. Teresa , Maiello Pauline , Tomko Jaime , Frye Lonnie James , Fillmore Daniel , Janssen Christopher , Klein Edwin , Lin Philana Ling 
Published: March 2014

ABSTRACT

Cynomolgus macaques infected with low-dose
Mycobacterium tuberculosis
develop both active tuberculosis and latent infection similar to those of humans, providing an opportunity to study the clinically silent early events in infection.
18
Fluorodeoxyglucose radiotracer with positron emission tomography coregistered with computed tomography (FDG PET/CT) provides a noninvasive method to measure disease progression. We sought to determine temporal patterns of granuloma evolution that distinguished active-disease and latent outcomes. Macaques (
n
= 10) were infected with low-dose
M. tuberculosis
with FDG PET/CT performed during infection. At 24 weeks postinfection, animals were classified as having active disease (
n
= 3) or latent infection (
n
= 6), with one “percolator” monkey. Imaging characteristics (e.g., lesion number, metabolic activity, size, mineralization, and distribution of lesions) were compared among active and latent groups. As early as 3 weeks postinfection, more pulmonary granulomas were observed in animals that would later develop active disease than in those that would develop latent infection. Over time, new lesions developed in active-disease animals but not in latent animals. Granulomas and mediastinal lymph nodes from active-disease but not latent animals consistently increased in metabolic activity at early time points. The presence of fewer lesions at 3 weeks and the lack of new lesion development in animals with latent infection suggest that innate and rapid adaptive responses are critical to preventing active tuberculosis. A greater emphasis on innate responses and/or rapid recruitment of adaptive responses, especially in the airway, should be emphasized in newer vaccine strategies.
Coping with heat stress during match-play tennis: Does an individualised hydration regimen enhance performance and recovery?
Authors: Périard Julien D , Racinais Sebastien , Knez Wade L , Herrera Christopher P , Christian Ryan J , Girard Olivier 
Published: March 2014

ObjectivesTo determine whether an individualised hydration regimen reduces thermal, physiological and perceptual strain during match-play tennis in the heat, and minimises alterations in neuromuscular function and physical performance postmatch and into recovery.Methods10 men undertook two matches for an effective playing time (ball in play) of 20 min (∼113 min) in ∼37°C and ∼33% RH conditions. Participants consumed fluids ad libitum during the first match (HOT) and followed a hydration regimen (HYD) in the second match based on undertaking play euhydrated, standardising sodium intake and minimising body mass losses.ResultsHYD improved prematch urine specific gravity (1.013±0.006 vs 1.021±0.009 g/mL; p<0.05). Body mass losses (∼0.3%), fluid intake (∼2 L/h) and sweat rates (∼1.6 L/h) were similar between conditions. Core temperature was higher during the first 10 min of effective play in HOT (p<0.05), but increased similarly (∼39.3°C) on match completion. Heart rate was higher (∼11 bpm) throughout HOT (p<0.001). Thermal sensation was higher during the first 7.5 min of effective play in HOT (p<0.05). Postmatch knee extensor and plantar flexor strength losses, along with reductions in 15 m sprint time and repeated-sprint ability (p<0.05), were similar in both conditions, and were restored within 24 h.ConclusionsBoth the hydration regimen and ad libitum fluid consumption allowed for minimal body mass losses (<1%). However, undertaking match-play in a euhydrated state attenuated thermal, physiological and perceptual strain. Maximal voluntary strength in the lower limbs and repeated-sprint ability deteriorated similarly in both conditions, but were restored within 24 h.
Clinical trial participants’ experiences of completing questionnaires: a qualitative study
Authors: Holmberg Christine , Karner Julia J , Rappenecker Julia , Witt Claudia M 
Published: March 2014

ObjectivesTo improve clinical study developments for elderly populations, we aim to understand how they transfer their experiences into validated, standardised self-completed study measurement instruments. We analysed how women (mean 78±8 years of age) participating in a randomised controlled trial (RCT) cognised study instruments used to evaluate outcomes of the intervention.SettingThe interview study was nested in an RCT on chronic neck pain using common measurement instruments situated in an elderly community in Berlin, Germany, which comprised of units for independent and assisted-living options.ParticipantsThe sample (n=20 women) was selected from the RCT sample (n=117, 95% women, mean age 76 (SD±8) years). Interview participants were selected using a purposive sampling list based on the RCT outcomes.OutcomesWe asked participants about their experiences completing the RCT questionnaires. Interviews were analysed thematically, then compared with the questionnaires.ResultsInterviewees had difficulties in translating complex experiences into a single value on a scale and understanding the relationship of the questionnaires to study aims. Interviewees considered important for the trial that their actual experiences were understood by trial organisers. This information was not transferrable by means of the questionnaires. To rectify these difficulties, interviewees used strategies such as adding notes, adding response categories or skipping an item.ConclusionsElderly interview participants understood the importance of completing questionnaires for trial success. This led to strategies of completing the questionnaires that resulted in ‘missing’ or ambiguous data. To improve data collection in elderly populations, educational materials addressing the differential logics should be developed and tested. Pilot testing validated instruments using cognitive interviews may be particularly important in such populations. Finally, when the target of an intervention is a subjective experience, it seems important to create a method by which participants can convey their personal experiences. These could be nested qualitative studies.Trial registration numberISRCTN77108101807.
Adapting data collection methods in the Australian Life Histories and Health Survey: a retrospective life course study
Authors: Kendig Hal , Byles Julie E , O'Loughlin Kate , Nazroo James Y , Mishra Gita , Noone Jack , Loh Vanessa , Forder Peta M 
Published: March 2014

ObjectiveIdeally, life course data are collected prospectively through an ongoing longitudinal study. We report adaptive multimethod fieldwork procedures that gathered life history data by mail survey and telephone interview, comparable with the face-to-face methods employed in the English Longitudinal Study on Ageing (ELSA).DesignThe Australian Life Histories and Health (LHH) Survey was a substudy of the Australian 45 and Up Study, with data collection methods modified from the ELSA Study. A self-complete questionnaire and life history calendar were completed by the participants, followed by a computer-assisted telephone interview recording key life events.ResultsThe LHH survey developed and tested procedures and instruments that gathered rich life history data within an ongoing Australian longitudinal survey on ageing. Data collection proved to be economical. The use of a self-complete questionnaire in conjunction with a life history calendar and coordinated computer-assisted telephone interview was successful in collecting retrospective life course information, in terms of being thorough, practical and efficient. This study has a diverse collection of data covering the life course, starting with early life experiences and continuing with socioeconomic and health exposures and outcomes during adult life.ConclusionsMail and telephone methodology can accurately and economically add a life history dimension to an ongoing longitudinal survey. The method is particularly valuable for surveying widely dispersed populations. The results will facilitate understanding of the social determinants of health by gathering data on earlier life exposures as well as comparative data across geographical and societal contexts.
Cerebral oximetry levels during CPR are associated with return of spontaneous circulation following cardiac arrest: an observational study
Authors: Singer Adam J , Ahn Anna , Inigo-Santiago Loren A , Thode Henry C , Henry Mark C , Parnia Sam 
Published: March 2014

ObjectivesCerebral oximetry using near-infrared spectroscopy measures regional cerebral oxygen saturation (rSO2) non-invasively and may provide information regarding the quality of cerebral oxygen perfusion. We determined whether the level of rSO2obtained during cardiopulmonary resuscitation is associated with return of spontaneous circulation (ROSC) and survival in Emergency Department (ED) patients presenting with cardiac arrest.MethodsWe conducted a retrospective, observational study of adult ED patients presenting at an academic medical centre with cardiac arrest in whom continuous cerebral oximetry was performed. Demographic and clinical data including age, gender, presenting rhythm and mean rSO2readings were abstracted. Cerebral oxygenation was measured with a commercially available oximeter.ResultsA convenience study sample included 59 patients ages 18–102 years (mean age 68.7 ± 14.9 years); 50 (84.7%) were men. Presenting rhythms included pulseless electrical activity (21), asystole (20) and ventricular fibrillation/tachycardia (17). 24 patients (40.6%) had ROSC and only 1 (1.7%) survived to hospital discharge. Patients with and without ROSC were similar in age and presenting cardiac rhythms. The mean of mean rSO2levels was higher in patients with ROSC, 43.8 (95% CI 40.1 to 47.6) compared with those without ROSC, 34.2 (95% CI 30.6 to 37.8); p=0.001. 91.7% of patients with ROSC had a rSO2of 30% or greater compared with 62.9% in those without ROSC (p=0.01). The area under the curve for mean rSO2as a predictor of ROSC was 0.76 (95% CI 0.64 to 0.89).ConclusionsIn ED patients with cardiac arrest higher cerebral oxygen saturations are associated with higher rates of ROSC.
Determinants of quality of life in advanced kidney disease: time to screen?
Authors: Iyasere Osasuyi , Brown Edwina A 
Published: March 2014

Abstract
The incidence of older patients with end stage renal disease is on the increase. This group of patients have multiple comorbidities and a high symptom burden. Dialysis can be life sustaining for such patients. But it is often at the expense of quality of life, which starts to decline early in the pathway of chronic kidney disease. Quality of life is also important to patients and is a major determinant in decisions regarding renal replacement. As a result, validated patient-reported outcome measures are increasingly used to assess quality of life in renal patients. Cognitive impairment, depression, malnutrition and function decline are non-renal determinants of quality of life and mortality. They are under-recognised in the renal population but are potentially treatable, if not preventable. This review article discusses aetio-pathogenesis, prevalence and impact of these four outcomes, advocating regular screening for early identification and management.
Bedside Tool for Predicting the Risk of Postoperative Atrial Fibrillation After Cardiac Surgery: The POAF Score
Authors: Mariscalco Giovanni , Biancari Fausto , Zanobini Marco , Cottini Marzia , Piffaretti Gabriele , Saccocci Matteo , Banach Maciej , Beghi Cesare , Angelini Gianni D. 
Published: March 2014

Background

Atrial fibrillation (
AF
) remains the most common complication after cardiac surgery. The present study aim was to derive an effective bedside tool to predict postoperative
AF
and its related complications.

Methods and Results

Data of 17 262 patients undergoing adult cardiac surgery were retrieved at 3 European university hospitals. A risk score for postoperative
AF
(
POAF
score) was derived and validated. In the overall series, 4561 patients (26.4%) developed postoperative
AF
. In the derivation cohort age, chronic obstructive pulmonary disease, emergency operation, preoperative intra‐aortic balloon pump, left ventricular ejection fraction <30%, estimated glomerular filtration rate <15 mL/min per m
2
or dialysis, and any heart valve surgery were independent
AF
predictors.
POAF
score was calculated by summing weighting points for each independent
AF
predictor. According to the prediction model, the incidences of postoperative
AF
in the derivation cohort were 0, 11.1%; 1, 20.1%; 2, 28.7%; and ≥3, 40.9% (
P
<0.001), and in the validation cohort they were 0, 13.2%; 1, 19.5%; 2, 29.9%; and ≥3, 42.5% (
P
<0.001). Patients with a
POAF
score ≥3, compared with those without arrhythmia, revealed an increased risk of hospital mortality (5.5% versus 3.2%,
P
=0.001), death after the first postoperative day (5.1% versus 2.6%,
P
<0.001), cerebrovascular accident (7.8% versus 4.2%,
P
<0.001), acute kidney injury (15.1% versus 7.1%,
P
<0.001), renal replacement therapy (3.8% versus 1.4%,
P
<0.001), and length of hospital stay (mean 13.2 versus 10.2 days,
P
<0.001).

Conclusions

The
POAF
score is a simple, accurate bedside tool to predict postoperative
AF
and its related or accompanying complications.
Visual Memory in Unilateral Spatial Neglect: Immediate Recall versus Delayed Recognition
Authors: Moreh Elior , Malkinson Tal Seidel , Zohary Ehud , Soroker Nachum 
Published: March 2014

AbstractPatients with unilateral spatial neglect (USN) often show impaired performance in spatial working memory tasks, apart from the difficulty retrieving “left-sided” spatial data from long-term memory, shown in the “piazza effect” by Bisiach and colleagues. This study's aim was to compare the effect of the spatial position of a visual object on immediate and delayed memory performance in USN patients. Specifically, immediate verbal recall performance, tested using a simultaneous presentation of four visual objects in four quadrants, was compared with memory in a later-provided recognition task, in which objects were individually shown at the screen center. Unlike healthy controls, USN patients showed a left-side disadvantage and a vertical bias in the immediate free recall task (69% vs. 42% recall for right- and left-sided objects, respectively). In the recognition task, the patients correctly recognized half of “old” items, and their correct rejection rate was 95.5%. Importantly, when the analysis focused on previously recalled items (in the immediate task), no statistically significant difference was found in the delayed recognition of objects according to their original quadrant of presentation. Furthermore, USN patients were able to recollect the correct original location of the recognized objects in 60% of the cases, well beyond chance level. This suggests that the memory trace formed in these cases was not only semantic but also contained a visuospatial tag. Finally, successful recognition of objects missed in recall trials points to formation of memory traces for neglected contralesional objects, which may become accessible to retrieval processes in explicit memory.
Functional Specialization within Macaque Dorsolateral Prefrontal Cortex for the Maintenance of Task Rules and Cognitive Control
Authors: Hussein Sabeeha , Johnston Kevin , Belbeck Brandon , Lomber Stephen G. , Everling Stefan 
Published: March 2014

Abstract
The abilities of switching between and maintaining task rules are fundamental aspects of goal-oriented behavior. The PFC is thought to implement the cognitive processes underling such rule-based behavior, but the specific contributions of the several cytoarchitecturally distinct subfields of PFC remain poorly understood. Here, we used bilateral cryogenic deactivation to investigate the relative contributions of two regions of the dorsolateral PFC (dlPFC)—the inferior dlPFC (idlPFC) area, consisting of the cortex lining the caudal principal sulcus, and the dorsally adjacent superior dlPFC (sdlPFC)—to different aspects of rule-based behavior. Macaque monkeys performed two variants of a task that required them to alternate unpredictably between eye movements toward (prosaccade) or away from (antisaccade) a visual stimulus. In one version of the task, the current rule was overtly cued. In the second, the task rule was uncued, and successful performance required the animals to detect rule changes on the basis of reward outcome and subsequently maintain the current task rule within working memory. Deactivation of the idlPFC impaired the monkeys' ability to perform pro- and antisaccades in the uncued task only. In contrast, deactivation of the sdlPFC had no effect on performance in either task. Combined deactivation of idlPFC and sdlPFC impaired performance on antisaccade, but not prosaccade, trials in both task variants. These results suggest that the idlPFC is required for mnemonic processes involved in maintenance of task rules, whereas both idlPFC and sdlPFC together are necessary for the deployment of the cognitive control required to perform antisaccades. Together, these data support the concept of a functional specialization of subregions within the dlPFC for rule-guided behavior.
On the Changing Contribution of Snow to the Hydrology of the Fraser River Basin, Canada
Authors: Kang Do Hyuk , Shi Xiaogang , Gao Huilin , Déry Stephen J. 
Published: March 2014

Abstract
This paper presents an application of the Variable Infiltration Capacity (VIC) model to the Fraser River basin (FRB) of British Columbia (BC), Canada, over the latter half of the twentieth century. The Fraser River is the longest waterway in BC and supports the world’s most abundant Pacific Ocean salmon populations. Previous modeling and observational studies have demonstrated that the FRB is a snow-dominated system, but with climate change, it may evolve to a pluvial regime. Thus, the goal of this study is to evaluate the changing contribution of snow to the hydrology of the FRB over the latter half of the twentieth century. To this end, a 0.25° atmospheric forcing dataset is used to drive the VIC model from 1949 to 2006 (water years) at a daily time step over a domain covering the entire FRB. A model evaluation is first conducted over 11 major subwatersheds of the FRB to quantitatively assess the spatial variations of snow water equivalent (SWE) and runoff (R). The ratio of the spatially averaged maximum SWE to R (RSR) is used to quantify the contribution of snow to the runoff in the 11 subwatersheds of interest. From 1949 to 2006, RSR exhibits a significant decline in 9 of the 11 subwatersheds (with p &lt; 0.05 according to the Mann–Kendall test statistics). To determine the sensitivity of RSR, the air temperature and precipitation in the forcing dataset are then perturbed. The ratio RSR decreases more significantly, especially during the 1990s and 2000s, when air temperatures have warmed considerably compared to the 1950s. On the other hand, increasing precipitation by a multiplicative factor of 1.1 causes RSR to decrease. As the climate continues to warm, ecological processes and human usage of natural resources in the FRB may be substantially affected by its transition from a snow to a hybrid (nival/pluvial) and even a rain-dominated system.