bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain in children and adolescents: prevalence, impact on daily life, and parents’ perception, a school survey
Authors: Haraldstad Kristin , Sørum Ragnhild , Eide Hilde , Natvig Gerd Karin , Helseth Sølvi 
Published: April 2010

Scand J Caring Sci; 2011; 25; 27–36

Pain in children and adolescents: prevalence, impact on daily life, and parents’ perception, a school survey Background:  Pain problems in children and adolescents have increased during the last 20 years and have been identified as an important public health problem.Aims:  The specific aims of the study were to study the prevalence of pain, its association with age, gender, and socio‐demographics, its frequency, duration, and type. A further aim is to describe the impact of pain on daily living, perceived triggers of pain, and correspondence between parents’ and children’s perceptions of pain.Design:  A cross‐sectional study, with a descriptive, exploratory design.Settings and participants:  A cluster sample of children and adolescents (age 8–18 years N = 1238,) and parents (n = 828), from 20 randomly selected schools in a region of Norway.Methods:  Data were collected using a structured self‐report questionnaire, the Lübeck Pain‐Screening Questionnaire (LPQ). The children filled in the questionnaires at school, while the parents completed the questionnaires at home.Results:  Sixty per cent of the children and adolescents reported pain within the previous 3 months. Pain increased with age, where girls aged 16–18 years reported the most pain. Total prevalence of chronic pain was 21%. Children reported impact on social life; inability to pursue hobbies, disturbed sleep, absence from school, and inability to meet friends because of pain. The girls reported significantly more frequently disturbed sleep, loss of appetite, and use of medication, compared to the boys. There was little agreement between parents and children regarding pain.Conclusions:  Pain is a common problem and influences the daily lives of children and adolescents. Many parents are unaware of the pain experienced by their children. There is a need for preventive programmes that also involve parents, school nurses, and teachers.
A case for incorporating phylogeography and landscape genetics into species distribution modelling approaches to improve climate adaptation and conservation planning
Authors: Scoble Jolene , Lowe Andrew John 
Published: April 2010

AbstractAim  We seek to demonstrate that whilst information derived from phylogeographic and landscape genetic approaches has been used broadly to further ecological and evolutionary hypothesis testing, it can also be used to further species modelling approaches, particularly where bioclimatic and demographic methodologies are to be combined to tackle climate change adaptation and conservation planning.Location  General application.Methods  We start with a review of species distribution modelling studies that have used data derived from molecular marker studies, and identify which parameters can realistically be derived from molecular marker studies for inclusion in species and ecosystem distribution prediction and conservation planning.Results  We find that the uptake of phylogeographic and landscape genetic methods to inform species distribution modelling studies has to date been limited (particularly the latter approaches), despite offering clear potential to improve species modelling approaches that aim to combine climatic envelope and demographic parameters. Using a series of cases studies, we demonstrate that phylogeographic approaches can be particularly useful for identifying biogeographic barriers and refugia, testing alternative demographic models, identifying concordant demographic patterns between species within a single ecosystem and testing temporal niche conservatism. We also find that landscape genetic approaches are particularly useful for quantifying landscape permeability and source/sink dynamics of meta‐populations and identifying adaptive variation in the landscape. A summary of parameters that are derivable from such studies for modelling and conservation applications is provided.Main conclusions  Molecular marker methods have much to offer species distribution modelling, particularly in the field of climate adaptation. Molecular information can inform on species historical dynamics and contemporary demography necessary to advance species modelling paradigms that seek to integrate climatic and demographic drivers. Furthermore, recognizing diversity below species level and incorporating this information into modelling frameworks will enable conservation managers to plan for the capture of areas of evolutionary potential.
Diabetic Patients on Peritoneal Dialysis
Authors: Passadakis Ploumis S. , Oreopoulos Dimitrios G. 
Published: April 2010

AbstractDuring the past two decades, a number of studies have tried to evaluate the clinical status of dialyzed diabetic patients and the factors that may affect their outcomes. However, only a small number of diabetic patients on peritoneal dialysis (PD) have been followed for over 5 years, which is largely because of the presence of various comorbid conditions at the start of dialysis, the coexisting, far‐advanced, target‐organ damage that may gradually progress during the course of dialysis and limit the long‐term survival on PD. On the contrary, among renal replacement therapies, survival of diabetic patients undergoing either PD or hemodialysis (HD) is probably similar, while diabetic patients on PD and HD have a lower actuarial survival than nondiabetic counterparts. This paper reviews our experience and the literature concerning the long‐term outcome of diabetic patients on PD.
Numerical Simulation of Thrombus Aspiration in Two Realistic Models of Catheter Tips
Authors: Pennati Giancarlo , Balossino Rossella , Dubini Gabriele , Migliavacca Francesco 
Published: April 2010

AbstractThrombus aspiration catheters are devices used to remove a blood clot from a vessel, usually prior to angioplasty or stent implantation. However, in vitro results showed that the use of different commercial devices could produce very different thrombus removals, suggesting a primary dependence on the distal tip configuration of the catheter. A computational methodology based on realistic catheter tip modeling was developed to investigate the factors affecting the thrombus suction. Two different designs were considered, either with a single central lumen or a combination of central and side holes. First, steady‐state aspiration of distilled water from a reservoir was simulated and compared with experimental tests. Subsequently, the aspiration of a totally occlusive thrombus, modeled as a high viscous fluid, was simulated solving a complex two‐phase (blood and thrombus) problem. In particular, the benefit of additional openings was investigated. Good matching between the steady‐state experimental and numerically simulated hydraulic behaviors allowed a validation of the numerical models. Numerical results of thrombus aspiration showed that the catheter with central and side holes had a worse performance if compared with the single central lumen catheter. Indeed, the inlets in contact with both blood and thrombus preferentially aspirate blood due to its much lower viscosity. This effect hindered the aspiration of thrombus. The amount of aspirated thrombus highly depends on the complex, two‐phase fluid dynamics occurring across the catheter tips. Results suggested that location of additional holes is crucial in the catheter aspiration performance.
Natural and Prosthetic Heart Valve Calcification: Morphology and Chemical Composition Characterization
Authors: Weska Raquel F. , Aimoli Cassiano G. , Nogueira Grínia M. , Leirner Adolfo A. , Maizato Marina J.S. , Higa Olga Z. , Polakievicz Bronislaw , Pitombo Ronaldo N.M. , Beppu Marisa M. 
Published: April 2010

AbstractCalcification is the most common cause of damage and subsequent failure of heart valves. Although it is a common phenomenon, little is known about it, and less about the inorganic phase obtained from this type of calcification. This article describes the scanning electron microscopy (SEM)/energy dispersive X‐ray spectroscopy and Ca K‐edge X‐ray absorption near edge structure (XANES) characterization performed in natural and bioprosthetic heart valves calcified in vivo (in comparison to in vitro‐calcified valves). SEM micrographs indicated the presence of deposits of similar morphology, and XANES results indicate, at a molecular level, that the calcification mechanism of both types of valves are probably similar, resulting in formation of poorly crystalline hydroxyapatite deposits, with Ca/P ratios that increase with time, depending on the maturation state. These findings may contribute to the search for long‐term efficient anticalcification treatments.
ORIGINAL ARTICLE: AIDS and optic neuritis in a rhesus monkey infected with the R5 clade C SHIV‐1157ipd3N4
Authors: García Anapatricia , Siddappa Nagadenahalli B. , Li Qingsheng , Haase Ashley T. , Paul Katherine , Stroud Fawn , Zhang Xiaodong , Fountain Jack A. , Villinger François , Novembre Francis J. , Else James G , Evan Secor W. , Ruprecht Ruth M. 
Published: April 2010

AbstractA Chinese rhesus macaque infected with the pathogenic CCR5‐tropic clade C simian‐human immunodeficiency virus, SHIV‐1157ipd3N4, had persistent viremia, depletion of CD4+ T cells to <200 cells/μl, opportunistic infections, coagulopathy, and gradual development of bilateral blindness. MRI revealed marked thickening of both optic nerves. Histopathological evaluation showed diffuse cellular infiltration at necropsy and a focus of SHIV‐infected cells. This is the first report of CNS pathology following chronic infection with an obligate R5 SHIV.
REGULATION IMPACT ASSESSMENT
Authors: SERPELL ANDREW 
Published: April 2010

Regulation impact assessment is a process by which policy makers can systematically assess the impact on affected stakeholder groups of various feasible alternatives for addressing an identified regulatory problem. This should enable better regulatory decisions to be made. The regulation impact assessment requirements for Commonwealth Government entities are set out in the Best Practice Regulation Handbook (OBPR, 2007).The general approach set out in the Handbook is sound. Clearly policy makers should first work out whether or not there is a problem before they attempt to fix it. Having clearly identified a problem, they should then carefully consider whether regulation is a justified response. Although the fundamental thinking behind the Handbook is sound, numerous issues and challenges will arise for government departments and agencies—as well as affected stakeholder groups—in complying with the new requirements.
Interactions between heart rate variability and pulmonary gas exchange efficiency in humans
Authors: Sin Peter Y. W. , Webber Matthew R. , Galletly Duncan C. , Ainslie Philip N. , Brown Stephen J. , Willie Chris K. , Sasse Alexander , Larsen Peter D. , Tzeng Yu‐Chieh 
Published: April 2010

The respiratory component of heart rate variability (respiratory sinus arrhythmia, RSA) has been associated with improved pulmonary gas exchange efficiency in humans via the apparent clustering and scattering of heart beats in time with the inspiratory and expiratory phases of alveolar ventilation, respectively. However, since human RSA causes only marginal redistribution of heart beats to inspiration, we tested the hypothesis that any association between RSA amplitude and pulmonary gas exchange efficiency may be indirect. In 11 patients with fixed‐rate cardiac pacemakers and 10 healthy control subjects, we recorded R–R intervals, respiratory flow, end‐tidal gas tension and the ventilatory equivalents for carbon dioxide
and oxygen
during ‘fast’ (0.25 Hz) and ‘slow’ paced breathing (0.10 Hz). Mean heart rate, mean arterial blood pressure, mean arterial pressure fluctuations, tidal volume, end‐tidal CO2,
and
were similar between pacemaker and control groups in both the fast and slow breathing conditions. Although pacemaker patients had no RSA and slow breathing was associated with a 2.5‐fold RSA amplitude increase in control subjects (39 ± 21 versus 97 ± 45 ms, P < 0.001), comparable
(main effect for breathing frequency, F(1,19) = 76.54, P < 0.001) and
reductions (main effect for breathing frequency, F(1,19) = 23.90, P < 0.001) were observed for both cohorts during slow breathing. In addition, the degree of
(r=−0.36, P= 0.32) and
reductions (r=−0.29, P= 0.43) from fast to slow breathing were not correlated to the degree of associated RSA amplitude enhancements in control subjects. These findings suggest that the association between RSA amplitude and pulmonary gas exchange efficiency during variable‐frequency paced breathing observed in prior human work is not contingent on RSA being present. Therefore, whether RSA serves an intrinsic physiological function in optimizing pulmonary gas exchange efficiency in humans requires further experimental validation.
Genomewide Screening for Novel Genetic Variations Associated with Ciprofloxacin Resistance in
Bacillus anthracis
Authors: Serizawa Masakuni , Sekizuka Tsuyoshi , Okutani Akiko , Banno Satomi , Sata Tetsutaro , Inoue Satoshi , Kuroda Makoto 
Published: April 2010

ABSTRACT

Fluoroquinolone (FQ) resistance of
Bacillus anthracis
is a serious concern in the fields of biodefense and bioterrorism since FQs are very effective antibiotics and are recommended as first-line treatment against this lethal bacterium. In this study, we obtained 2 strains of
B. anthracis
showing resistance or intermediate resistance to ciprofloxacin (CIP) by a stepwise selection procedure with increasing CIP concentrations. Fifteen genetic variations were identified between the parental and CIP-resistant strains by next-generation sequencing. Nonsynonymous mutations in the quinolone resistance-determining region (QRDR) of type II DNA topoisomerase were identified in the resistant strain but not in the intermediate-resistant strain. The GBAA0834 (TetR-type transcriptional regulator) locus was also revealed to be a novel “mutation hot spot” that leads to the increased expression of multidrug efflux systems for CIP resistance. As an initial step of CIP resistance in
B. anthracis
, such disruptive mutations of GBAA0834 appear to be more easily acquired than those in an essential gene, such as that encoding type II DNA topoisomerase. Such an intermediate-resistant phenotype could increase a cell population under CIP-selective pressure and might promote the emergence of highly resistant isolates. Our findings reveal, in addition to QRDR, crucial genetic targets for the investigation of intermediate resistance of
B. anthracis
to FQs.
Pharmacokinetics of Darunavir at 900 Milligrams and Ritonavir at 100 Milligrams Once Daily when Coadministered with Efavirenz at 600 Milligrams Once Daily in Healthy Volunteers
Authors: Soon Gaik H. , Shen Ping , Yong Eu-Leong , Pham Paul , Flexner Charles , Lee Lawrence 
Published: April 2010

ABSTRACTRitonavir-boosted darunavir with efavirenz may be considered a nucleoside-sparing regimen for treatment-naïve HIV-infected patients. However, the pharmacokinetics of this combination administered once daily have not been studied. We conducted a three-period interaction study with healthy volunteers. The subjects were given darunavir at 900 mg with ritonavir at 100 mg once daily for 10 days. Efavirenz at 600 mg once daily was added for 14 days. Darunavir-ritonavir was then stopped and efavirenz alone was given for 14 days. At the end of each period, blood was taken predosing and for up to 24 h postdosing to measure the drug concentrations. We recruited seven males and five females ages 24 to 49 years and weighing 50 to 83 kg. The darunavir trough concentrations were reduced after efavirenz administration (geometric mean ratio [GMR], 0.43; 90% confidence interval [CI], 0.32 to 0.57];P< 0.001). The mean darunavir trough concentrations were 1,180 ng/ml (standard deviation, 1,138 ng/ml) after efavirenz administration, but all darunavir trough concentrations were above the 50% effective concentration (EC50) of 55 ng/ml for the wild-type virus. For darunavir, the area under the concentration-time curve from 0 to 24 h (AUC0-24) (GMR, 0.86; 90% CI, 0.75 to 0.97;P= 0.05) and the half-life (GMR, 0.56; 90% CI, 0.49 to 0.65;P< 0.001) were also significantly reduced. The darunavir peak concentrations were not significantly changed (GMR, 0.92; 90% CI, 0.82 to 1.03;P= 0.23). The ritonavir trough concentrations (GMR, 0.46; 90% CI, 0.33 to 0.63;P= 0.001), AUC0-24(GMR, 0.74; 90% CI, 0.64 to 0.86;P= 0.004), and half-life (GMR, 0.80; 90% CI, 0.75 to 0.86;P< 0.001) were also significantly reduced. The efavirenz half-life was significantly longer when it was coadministered with darunavir-ritonavir than when it was given alone (GMR, 1.66; 90% CI, 1.24 to 2.23;P= 0.01), but there were no differences in the efavirenz trough or peak concentration or AUC0-24when it was coadministered with darunavir-ritonavir. Efavirenz reduced the trough concentrations of darunavir significantly, but the concentrations remained above the EC50for the wild-type virus. This regimen should be evaluated with treatment-naïve patients with no preexisting resistance.
Population Pharmacokinetics of Doripenem Based on Data from Phase 1 Studies with Healthy Volunteers and Phase 2 and 3 Studies with Critically Ill Patients
Authors: Nandy Partha , Samtani Mahesh N. , Lin Rachel 
Published: April 2010

ABSTRACT

A population pharmacokinetic model of doripenem was constructed using data pooled from phase 1, 2, and 3 studies utilizing nonlinear mixed effects modeling. A 2-compartment model with zero-order input and first-order elimination best described the log-transformed concentration-versus-time profile of doripenem. The model was parameterized in terms of total clearance (CL), central volume of distribution (

V
c

), peripheral volume of distribution (

V
p

), and distribution clearance between the central and peripheral compartments (
Q
). The final model was described by the following equations (for
j
th subject): CL

j

(liters/h) = 13.6·(CL
CR

j

/98 ml/min)
0.659
·(1 + CL
race

j

[0 for Caucasian]);

V
c

j

(liters) = 11.6·(weight

j

/73 kg)
0.596
;

Q
j

(liters/h) = 4.74·(weight

j

/73)
1.06
; and

V
p

j

(liters) = 6.04·(CL
CR

j

/98 ml/min)
0.417
·(weight

j

/73 kg)
0.840
·(age

j

/40 years)
0.307
. According to the final model, population mean parameter estimates and interindividual variability (percent coefficient of variation [% CV]) for CL (liters/h),

V
c

(liters),

V
p

(liters), and
Q
(liters/h) were 13.6 (19%), 11.6 (19%), 6.0 (25%), and 4.7 (42%), respectively. Residual variability, estimated using three separate additive residual error models, was 0.17 standard deviation (SD), 0.55 SD, and 0.92 SD for phase 1, 2, and 3 data, respectively. Creatinine clearance was the most significant predictor of doripenem clearance. Mean Bayesian clearance was approximately 33%, 55%, and 76% lower for individuals with mild, moderate, or severe renal impairment, respectively, than for those with normal renal function. The population pharmacokinetic model based on healthy volunteer data and patient data informs us of doripenem disposition in a more general population as well as of the important measurable intrinsic and extrinsic factors that significantly influence interindividual pharmacokinetic differences.
Cellular Pharmacokinetics of the Novel Biaryloxazolidinone Radezolid in Phagocytic Cells: Studies with Macrophages and Polymorphonuclear Neutrophils
Authors: Lemaire Sandrine , Tulkens Paul M. , Van Bambeke Françoise 
Published: April 2010

ABSTRACT
Radezolid (RX-1741) is the first biaryloxazolidinone in clinical development. It shows improved activity, including against linezolid-resistant strains. Radezolid differs from linezolid by the presence of a biaryl spacer and of a heteroaryl side chain, which increases the ionization and hydrophilicity of the molecule at physiological pH and confers to it a dibasic character. The aim of this study was to determine the accumulation and subcellular distribution of radezolid in phagocytic cells and to decipher the underlying mechanisms. In THP-1 human macrophages, J774 mouse macrophages, and human polymorphonuclear neutrophils, radezolid accumulated rapidly and reversibly (half-lives of approximately 6 min and 9 min for uptake and efflux, respectively) to reach, at equilibrium, a cellular concentration 11-fold higher than the extracellular one. This process was concentration and energy independent but pH dependent (accumulation was reduced to 20 to 30% of control values for cells in medium at a pH of <6 or in the presence of monensin, which collapses pH gradients between the extracellular and intracellular compartments). The accumulation at equilibrium was not affected by efflux pump inhibitors (verapamil and gemfibrozil) and was markedly reduced at 4°C but was further increased in medium with low serum content. Subcellular fractionation studies demonstrated a dual subcellular distribution for radezolid, with ∼60% of the drug colocalizing to the cytosol and ∼40% to the lysosomes, with no specific association with mitochondria. These observations are compatible with a mechanism of transmembrane diffusion of the free fraction and partial segregation of radezolid in lysosomes by proton trapping, as previously described for macrolides.
Cellular Pharmacodynamics of the Novel Biaryloxazolidinone Radezolid: Studies with Infected Phagocytic and Nonphagocytic cells, UsingStaphylococcus aureus,Staphylococcus epidermidis,Listeria monocytogenes, andLegionella pneumophila
Authors: Lemaire Sandrine , Kosowska-Shick Klaudia , Appelbaum Peter C. , Verween Gunther , Tulkens Paul M. , Van Bambeke Françoise 
Published: April 2010

ABSTRACTRadezolid is a novel biaryloxazolidinone in clinical development which shows improved activity, including against linezolid-resistant strains. In a companion paper (29), we showed that radezolid accumulates about 11-fold in phagocytic cells, with ∼60% of the drug localized in the cytosol and ∼40% in the lysosomes of the cells. The present study examines its activity against (i) bacteria infecting human THP-1 macrophages and located in different subcellular compartments (Listeria monocytogenes, cytosol;Legionella pneumophila, vacuoles;Staphylococcus aureusandStaphylococcus epidermidis, mainly phagolysosomal), (ii) strains ofS. aureuswith clinically relevant mechanisms of resistance, and (iii) isogenic linezolid-susceptible and -resistantS. aureusstrains infecting a series of phagocytic and nonphagocytic cells. Radezolid accumulated to similar levels (∼10-fold) in all cell types (human keratinocytes, endothelial cells, bronchial epithelial cells, osteoblasts, macrophages, and rat embryo fibroblasts). At equivalent weight concentrations, radezolid proved consistently 10-fold more potent than linezolid in all these models, irrespective of the bacterial species and resistance phenotype or of the cell type infected. This results from its higher intrinsic activity and higher cellular accumulation. Time kill curves showed that radezolid's activity was more rapid than that of linezolid both in broth and in infected macrophages. These data suggest the potential interest of radezolid for recurrent or persistent infections where intracellular foci play a determinant role.