Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigation of the variability of etoposide pharmacokinetics in children.

PROBLEM The interindividual variation of etoposide pharmacokinetics under different therapeutic schedules and the rationale of dose reduction in young children and newborns were investigated in the present study. PATIENTS AND METHODS We evaluated pharmacokinetic parameters during short-term infusion in 21 therapy cycles (18 children) on different therapeutic schedules (66-200 mg/m2). In 33 patients state levels (Css) during continuous infusion of 125 mg/m2/96 h were analyzed by an HPLC-method. RESULTS During short-term infusion half-life (3.3 +/- 0.7 h) and total body clearance (26 +/- 6 ml/min/m2) showed a relatively narrow range. Calculation of the area under the curve was standardized to a dosage of 100 mg/m2 (AUC/[100 mg/m2]). The AUC then was 68 +/- 17 (micrograms.h/ml)/(100 mg/m2) with a coefficient of variation of 25%. In the subgroup of 10 patients who received 150 mg/m2 the AUC was 106 +/- 15 micrograms.h/ml with only 14% coefficient of variation. In children < 2 years, pharmacokinetic parameters were within the normal range. Calculation of the doses the short-term infusion per kg resulted in a dose reduction or 31% (mean, n = 5) and in 22% (mean) lower AUC's. With continuous infusion of 125 mg/m2 etoposide the interpatient variability was greater with a 33% coefficient of variation of the Css (4.4 +/- 1.4 micrograms/ml; n = 24). Calculation of the doses per kg (age < 1 year) or 2/3.kg resulted in reduced Css. Standardization of these levels showed Css (125 mg/m2) of 4.6 +/- 1.4 micrograms/ml and a coefficient of variation of 31%. CONCLUSIONS Interpatient variability of etoposide pharmacokinetics at least during short-term infusion is limited. Dose reduction is not substantiated in children < 2 years by our pharmacokinetic data.
Suicide prevention at a United States Navy training command.

In a 2-year retrospective study, suicide prevention efforts produced a significant reduction in suicide attempts at a U.S. Navy training command. Evidence was presented that suicide prevention may be a more pressing issue at training commands than operational commands. The approach described here focused on instructors rather than on the students who were the usual patients presenting with suicidal ideation or attempts. Instructors were taught how to identify and help individuals at risk and how to get help for them.
The KEGG database.

KEGG (http://www.genome.ad.jp/kegg/) is a suite of databases and associated software for understanding and simulating higher-order functional behaviours of the cell or the organism from its genome information. First, KEGG computerizes data and knowledge on protein interaction networks (PATHWAY database) and chemical reactions (LIGAND database) that are responsible for various cellular processes. Second, KEGG attempts to reconstruct protein interaction networks for all organisms whose genomes are completely sequenced (GENES and SSDB databases). Third, KEGG can be utilized as reference knowledge for functional genomics (EXPRESSION database) and proteomics (BRITE database) experiments. I will review the current status of KEGG and report on new developments in graph representation and graph computations.
Protein structure by mechanical triangulation

Knowledge of protein structure is essential to understand protein function. High-resolution protein structure has so far been the domain of ensemble methods. Here, we develop a simple single-molecule technique to measure spatial position of selected residues within a folded and functional protein structure in solution. Construction and mechanical unfolding of cysteine-engineered polyproteins with controlled linkage topology allows measuring intramolecular distance with angstrom precision. We demonstrate the potential of this technique by determining the position of three residues in the structure of green fluorescent protein (GFP). Our results perfectly agree with the GFP crystal structure. Mechanical triangulation can find many applications where current bulk structural methods fail.
Bibliometric Analysis of Nursing Research in Taiwan 1991-2004

&NA; This study examined nursing research performance in Taiwan from 1991 to 2004 by conducting bibliometric analysis of papers published by researchers affiliated with nursing institutes in Taiwan. Bibliometric information of papers that were published between 1991 and 2004 and had contact address including the words “Taiwan”, and “nursing” were downloaded from the ISI Web of Knowledge website. The information used for this research included number of papers, number of authors, number of references listed, impact factors of publishing journals, times cited, and whether the paper was written through international or domestic collaboration. The information was coded and tabulated. Bibliometric characteristics were compared between 1995-1999 and 2000-2004. Furthermore, an exponential model was fitted to show the past growth trend in research outputs. The results showed that there was a significant growth in quantity of papers from 1991 to 2004. In general, recent papers had averaged more authors, more domestic collaboration, more international collaboration, higher impact factors, and more references listed than earlier papers. Papers written with collaboration tended to have a higher average number of authors and more references listed, and tended to be published in journals with higher impact factors. The exponential model proved to be in good fit with the past growth pattern. The authors speculate that the recent increase in research collaboration, both internationally and domestically, may have contributed to the significant increase in output. It is not clear whether the growth in quantity of papers will continue or for how long. Based on past data, however, no sign of leveling off has been observed. More research is needed to understand what societal and individual level factors were involved in fueling such a dramatic increase in quantity in the last decade. Furthermore, as the quantity of papers has increased steadily, more focus can be placed on improving the quality of research papers.
Laboratory strength of glass ionomer cement, compomers, and resin composites.

PURPOSE The study evaluates the compressive, flexural, and diametral tensile strengths of 8 core build-up materials from different material classes (highly viscous glass ionomer cement, autocured resin composite, and compomers). MATERIALS AND METHODS All materials were manipulated according to the manufacturers' recommendations for use as core materials. At a temperature of 23.0 +/- 1.0 degrees C the properties of compressive, diametral tensile and flexural strength were determined using a universal testing machine at 15 minutes, 1 hour, and 24 hours after material preparation. Using one-way analysis of variance (ANOVA), multiple mean value comparisons were performed to determine significant differences (p< or =.05) between the core restoration materials. RESULTS The values for compressive strength varied from 40.3 +/- 5.2 MPa (compomer) to 237.4 +/- 37.3 MPa (autocured resin composite) for the 3 measurement times. At 15 minutes, 1 hour, and 24 hours after first mixing, the ANOVA showed significant differences (p < or =.05) between the resin composite Core Paste and all of the other materials. Diametral tensile strengths ranged from 5.5 +/- 1.1 MPa for glass ionomer cement to 39.1 +/- 2.9 MPa for composite core material. Three-point flexural strength showed values ranging from 12.1 +/- 2.5 MPa for glass ionomer cement to 92.1 +/- 9.7 MPa for compomer between the 3 measurement times. CONCLUSIONS Setting time influences the mechanical properties of the materials tested in this study. Autopolymerizing resin composite Core Paste demonstrated greater compressive and flexural strengths at the 3 measurement times than the other materials tested. Reinforced composites, in comparison to the autocured resin composites, yielded no improvement in tensile strength. Flexural and tensile strengths of the glass ionomer cement were lower than those of autocured resin composites and compomers.
Citalopram as an adjuvant in chronic schizophrenia: a double‐blind placebo‐controlled study

The effects of citalopram — the most selective serotonin reuptake inhibitor on the market — on psychopathological symptoms were studied in chronic schizophrenic patients on a stable regimen of neuroleptic medication. Outpatients suffering from schizophrenic disorder (DSM‐III‐R) with Positive and Negative Symptom Scale (PANSS) scores higher than 50 were included in a double‐blind placebo‐controlled add‐on study. The daily dose of citalopram was 20 mg in the first week and 40 mg for the remaining period. A total of 90 patients (45 patients receiving citalopram and 45 receiving placebo) completed the 12‐week trial. There were no changes in neuroleptic plasma levels during the trial. There was a significant decrease in total PANNS scores during the trial, although no statistically significant differences between the citalopram group and the placebo group were revealed. The number of responders in terms of severity of illness (CGI) was higher and the increase in subjective well‐being (VAS) was greater in patients on citalopram than in those receiving placebo. There were no significant differences in the occurrence of side‐effects. It is concluded that, in chronic schizophrenic out‐patients, citalopram has no clear effect on the psychopathological symptoms; it may improve the general clinical condition, and it appears to increase the subjective well‐being of these patients. Citalopram appears to be safe when used to treat schizophrenic patients who are receiving concomitant neuroleptic treatment.
In vivo induction of the nitric oxide pathway in hepatocytes after injection with irradiated malaria sporozoites, malaria blood parasites or adjuvants

The mechanisms responsible for malarial immunity induced by repetitive injections of X‐irradiated sporozoites have not been fully established. We demonstrate here that a single injection of irradiated sporozoites induced, as soon as 24 h after, a non‐permissive state to hepatocyte reinfection with sporozoites in vitro. The same effect was observed when malarial blood forms, irradiated promastigotes of Leishmania infantum, adjuvants (muramyl dipeptide, poly acidylic uridylic) or interferon‐γ was injected. Activation of the nitric oxide (NO) pathway in the hepatocyte by these factors was found to be responsible for hepatocyte refractory status. Additionally, this metabolic pathway is involved in protection given by repeated injections of irradiated sporozoites since protection could be reversed by treating mice at the time of sporozoite challenge with a competitive inhibitor (NG‐monomethyl‐L‐arginine) of the NO pathway. These results suggest that, in view of an antisporozoite vaccine, further studies are needed to find out how to activate specifically a long‐lasting nonspecific immune response.
When the solution is part of the problem: problem solving in elderly suicide attempters

Depression, loss, and physical illness are associated with suicide in the elderly. However, the nature of individual vulnerability remains poorly understood. Poor problem solving has been suggested as a risk factor for suicide in younger adults. Unresolved problems may create an accumulation of stressors. Thus, those with perceived deficits in problem‐solving ability may be predisposed to suicidal behavior. To test this hypothesis, we investigated whether elderly suicide attempters perceived their problem solving as deficient.
Comparative analysis of signature genes in PRRSV-infected porcine monocyte-derived cells to different stimuli

Monocyte-derived DCs (mDCs) are major target cells in porcine reproductive and respiratory syndrome virus (PRRSV) pathogenesis; however, the plasticity of mDCs in response to activation stimuli and PRRSV infection remains unstudied. In this study, we polarized mDCs, and applied genome-wide transcriptomic analysis and predicted protein-protein interaction networks to compare signature genes involved in mDCs activation and response to PRRSV infection. Porcine mDCs were polarized with mediators for 30 hours, then mock-infected, infected with PRRSV strain VR2332, or a highly pathogenic PRRSV strain (rJXwn06), for 5 h. Total RNA was extracted and used to construct sequencing libraries for RNA-Seq. Comparisons were made between each polarized and unpolarized group (i.e. mediator vs. PBS), and between PRRSV-infected and uninfected cells stimulated with the same mediator. Differentially expressed genes (DEG) from the comparisons were used for prediction of interaction networks affected by the viruses and mediators. The results showed that PRRSV infection inhibited M1-prone immune activity, downregulated genes, predicted network interactions related to cellular integrity, and inflammatory signaling in favor of M2 activity. Additionally, the number of DEG and predicted network interactions stimulated in HP-PRRSV infected mDCs was superior to the VR-2332 infected mDCs and conformed with HP-PRRSV pathogenicity.
Efficacy of Percutaneous Cementoplasty for Bone Metastasis from Hepatocellular Carcinoma

Objective: To assess the efficacy of percutaneous cementoplasty for painful bone metastasis from hepatocellular carcinoma (HCC). Methods: Cementoplasty was performed for 22 metastatic bone tumors in 13 patients. All patients had intractable pain and were diagnosed as metastatic bone tumor from HCC. The ostyneedle was inserted in the center of the site of bone metastasis under CT guidance. VAS score, Tokuhashi score and Frankel score were used for assessment of the efficacy of cementoplasty. We also assessed the response to treatment, adverse events and prognosis. Results: Only the VAS score, but not Tokuhashi and Frankel scores, improved after cementoplasty. Cementoplasty for painful bone metastasis provided relief of severe pain but did not improve prognosis, neurological function or survival. Eleven of 13 (85%) patients showed CR or PR and the mean pain-free period was 5 months, including a 10-month pain-free period in one case. No major complications were encountered. Conclusions: Percutaneous cementoplasty can provide pain relief and improvement of quality of life, though without survival benefits, for HCC patients with painful bone metastasis.
Use of a nutrition support protocol to increase enteral nutrition delivery in critically ill patients.

BACKGROUND Early enteral nutrition is recommended for patients in intensive care units, but nutrition provision is often hindered by a variety of unit-specific problems. OBJECTIVES To evaluate the impact of a nutrition support protocol on nutrition prescription and delivery in the intensive care unit. METHODS Nutrition-related data from 73 patients receiving mechanical ventilation who were treated in an adult medical intensive care unit before introduction of an enteral nutrition support protocol were retrospectively compared with data for 87 patients admitted after implementation of the protocol. RESULTS After implementation of the protocol, enteral nutrition was started significantly earlier (P = .007) and enteral feeding goals were reached significantly faster (6 vs 10 days, P < .001) than before. Prescription of enteral nutrition on the first day of invasive mechanical ventilation increased from 38% before to 54% after (P = .03) implementation of the protocol. Prescribed and delivered nutrition doses on the first 2 days of mechanical ventilation also increased significantly (P < .001) after the protocol was implemented. Nasojejunal feeding tubes were used in 52% of patients before and 56% of patients after protocol implementation P = . 63). Jejunal tubes were placed earlier after the protocol was implemented than before (median 5 vs 6.5 days), and when a jejunal tube was in place, feeding goals were reached faster (median 2 vs 3 days, P = .002). CONCLUSION Implementing an enteral nutrition support protocol shortened the time to reach feeding goals. Jejunal feeding tubes were necessary in more than half of the patients, and with a jejunal feeding tube in place, feeding goals were reached rapidly.
Modules sémantiques robustes pour une réutilisation saine en DL-lite

L'extraction de modules a partir d'ontologies a ete recemment etudie dans le cadre des logiques de description, qui sont au coeur des langages modernes d'ontologies. Dans cet article, nous definissons une nouvelle notion de modules semantiques capturant a la fois les modules obtenus par extraction d'un sous-ensemble d'une Tbox ou par "forgetting" de concepts et de roles d'une Tbox. Nous definissons et etudions ensuite la reutilisation saine d'un module semantique d'une Tbox globale afin de construire des Aboxes locales et de les interroger soit independamment, soit de facon conjointe avec la Abox globale. Afin que la Abox locale (associee au module) et que la Abox globale (associee a la Tbox initiale) puissent evoluer independamment, mais de maniere coherente, nous generalisons la notion d'extension conservative de requete et nous l'etendons au test de consistance. Enfin, nous fournissons des algorithmes et des resultats de complexite pour le calcul de modules semantiques minimaux et robustes dans DL-liteF et DL-liteR. Ces dialectes sont membres de la famille DL-lite qui a ete specialement definie pour l'interrogation efficace de grandes masses de donnees.
Catecholamine Use is Associated With Enterocyte Damage in Critically Ill Patients

ABSTRACT Small bowel damage is frequent but underdiagnosed among critically ill patients with shock. High catecholamine doses may have a deleterious effect on mesenteric blood flow. Plasma intestinal fatty acid–binding protein (I-FABP) concentration is a marker of enterocyte damage, whereas plasma citrulline concentration is a marker of functional enterocyte mass. We hypothesized that high doses of catecholamines in critically ill patients may be associated with enterocyte damage. This study aimed to determine the link between catecholamine use and dose with enterocyte damage. This is a prospective observational study performed in a large regional university teaching hospital. Critically ill patients requiring epinephrine and/or norepinephrine at admission to a medical intensive care unit (ICU) were included, as well as controls not receiving catecholamines. We evaluated at admission plasma I-FABP and citrulline concentrations, abdominal perfusion pressure (APP), and variables relating to prognosis and treatment. Patients were categorized according to the quartiles of catecholamine dose at ICU admission. Sixty critically ill patients receiving catecholamines and 27 not receiving catecholamines were included. Plasma I-FABP was higher among patients receiving catecholamine than in controls. Among patients receiving catecholamines, a dose of 0.48 &ggr; kg−1 min−1 or more at ICU admission was associated with a higher I-FABP concentration. A Sepsis-related Organ Failure Assessment score higher than 11 and plasma I-FABP more than 524 pg mL−1 at ICU admission were independently associated with 28-day mortality (odds ratio, 4.0 [1.24–12.95] and odds ratio, 4.90 [1.44–16.6], respectively). Catecholamine use is associated with I-FABP elevation in critically ill patients. Critically ill patients receiving more than 0.48 &ggr; kg−1 min−1 of epinephrine and/or norepinephrine at ICU admission have high I-FABP concentrations. This suggests that enterocyte damage reflects the severity of shock, and an adverse effect of catecholamines per se is possible.
Self-Selection of Auditors and Audit Pricing in Private Firms

Prior research has examined audit pricing for publicly held firms and provided some evidence of a Big 8 premium in pricing. We investigate audit pricing among private firms, and provide evidence that private firms do not pay such a premium on average. The relatively greater degree of dispersion in auditor choice (between Big 5 and non‐Big 5 auditors) in our large sample of privately held audit clients allows us to predict the auditor choice for each firm and to control for potential self‐selection. We reject the null hypothesis that clients are randomly allocated across Big 5 and non‐Big 5 auditors. Using standard OLS regressions, we document a Big 5 premium; however this premium vanishes once we control for self‐selection bias. Moreover, we find that client firms choosing Big 5 auditors generally would have faced higher fees had they chosen non‐Big 5 auditors, given their firm‐specific characteristics. Our results are consistent with audit markets for private firms being segmented along cost‐effective li.
An Examination of Computer-Mediated Communication for Engineering-Related Tasks

This study aims to understand the course of communication media selection in cross-organizational engineering teams on high-tech product development. We argue that, although collaborative engineering tasks have been highly internationalized, communication media development for the pervasive global technological activities has not been sufficient, and thus when complex product design in connection with numerous technological issues is discussed on computer-mediated communication, the challenges can be more. This study conducted a multiple-case study approach, involving four case studies regarding inter-organizational collaborations on high-tech product developments. Participant observation was employed as the primary method of data collection, and extensive data was collected and analyzed. This research has found that high reliance on email communication among the participant organizations ultimately contributed to conflict occurrence, and the research findings for theoretical and practical implications are discussed.
Assessment of Commercialization Strategy Using R&D Capability

Purpose – The purpose of this paper is to present a cooperation model identifying the R&D capability as the central driver of startup commercialization strategy, by which new startups can evaluate their relative R&D capability and consequently choose an appropriate commercialization strategy.Design/methodology/approach – A cooperation model has been constructed, and drawing upon the patent data of 91 aluminum nitride manufacturers, the implications of R&D capability for commercialization strategy are illustrated.Findings – The authors' analysis suggests that competitive interaction between startup innovators and established firms depends on the R&D capability of the startup innovators, which can be evaluated by patent data.Practical implications – For technologically efficient firms, a high level of integration to achieve the benefits of economies of scope will lead to more profits. However, for technologically inefficient firms, maintaining a low level of integration to achieve the benefits of specializa.
Article Title

This paper details a new decision support that adds a proactive function to the actual line aircraft maintenance turn-around-time (TAT) process, where next-flight decisions are assisted by the health assessment function of the integrated vehicle health management (IVHM) of an aircraft. The ‘operational risk assessment’ concept appears an extended function supported on the IVHM information for calculating and evaluating the operational risk for aircraft and fleet operations. It creates or reshapes maintenance plans based on predictions of the future maintenance relevant events (e.g. component-degradation-driven repair or replacement events) and its impact on the operational planning of the aircraft/fleet. ‘Operational risk assessment’ makes it possible to turn the scheduled line maintenance into a proactively defined maintenance. The paper also illustrates the first step involved in this approach: ‘condition view’ function, which is responsible for the provision of the remaining useful life (RUL) prediction of a health managed component. This function provides the basis for the operational risk estimation on the aircraft in order to identify maintenance actions that can be deferred.