bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ventilator‐Associated Pneumonia Bundled Strategies: An Evidence‐Based Practice
Authors: O'Keefe‐McCarthy Sheila , Santiago Cecilia , Lau Gemma 
Published: December 2008

ABSTRACT Background: Ventilator‐associated pneumonia (VAP) is an ongoing challenge for critical care nurses as they use current evidence‐based strategies to decrease its incidence and prevalence. Mechanical intubation negates effective cough reflexes and impedes mucociliary clearance of secretions, causing leakage and microaspiration of virulent bacteria into the lungs. VAP is responsible for 90% of nosocomial infections and occurs within 48 hours of intubation. VAP is a major health care burden in terms of mortality, escalating health care costs, increased length of ventilator days and length of hospital stay. Aim: (1) To provide a review of the literature on VAP bundle (VAPB) practices. (2) To describe the etiology and risk factors and define bundled practices. (3) To discuss an explanatory framework that promotes knowledge translation of VAPBs into clinical settings. (4) To identify areas for further research and implications for practice to decrease the incidence of VAP. Methods: Electronic searches in MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Collaboration were conducted using keywords specific to VAP. The inclusion criteria were: (1) Studies were original quantitative research published in an English peer‐reviewed journal for the years 1997 to 2007. (2) Each study included an examination of bundled practices. (3) The clinical outcomes of critically ill adults with VAP were assessed. The studies were identified from the bibliographies of key references. Six studies were accepted based on the inclusion criteria. Each contributing author conducted the review and analysis of selected studies independently. The findings were compared and contrasted by all authors to establish consensus. Results: Evidence shows that VAPB practices decrease VAP rates. Bundled practices result in decreased ventilator days, intensive care unit length of stay, and mortality rates. A strong association was seen, with an increased clinician compliance with VAPB protocols with decreased VAP rates. Conclusions and Implications: Methodologically robust randomized controlled trials are required to examine the efficacy of VAPBs and determine causality between VAPBs and clinical outcomes. Organizational commitment is needed to adopt a conceptual framework that promotes effective knowledge translation, incorporating factors of evidence, context, and facilitation of VAPBs into clinical settings. Instituting nurse‐led intervention champion leaders to facilitate reliable and consistent implementation of VAPBs into practice is warranted.
Efficacy and Safety of Medium and Long-Term Tadalafil Use in Spinal Cord Patients with Erectile Dysfunction
Authors: Lombardi Giuseppe , Macchiarella Angelo , Cecconi Filippo , Del Popolo Giulio 
Published: December 2008

ABSTRACT

Introduction
The efficacy of phosphodiesterase type 5 inhibitors for a broad spectrum of erectile dysfunction (ED) is largely reported in literature. Data are lacking concerning medium and long-term effects and safety of these treatments.

Aim
The aim of this study was to evaluate the efficacy and safety of medium and long-term use of tadalafil in subjects with ED because of spinal cord injury (SCI).

Methods
Phase 1: From March 2003 to March 2007, 103 SCI patients with ED, mean age 39 years, were given 10 mg of tadalafil after a 4-week treatment-free period. For patients with a score lower than 26 in the erectile domain of the International Index of Erectile Function (IIEF15) and with total unsuccessful sexual attempts of more than 25% according to the Sexual Encounter Profile questions 2 and 3 (SEP2–3), the dosage of tadalafil was increased to 20 mg.
Phase 2: Only responding patients entered phase 2 where the subjects were evaluated in office visits every 6 months using the IIEF15 questionnaire and a diary reporting the day and time the drug was taken. All final visits were concluded by May 2008.

Main Outcome Measures
The improvement of ED was measured using the IIEF15 and the SEP2–3 questions.

Results
Twenty-nine patients were excluded from phase 2: Twenty-seven did not respond to the drug and two left the study because of mild drawbacks. During the 6-month follow-up, nine left the study. Sixty-five individuals continued treatment with median follow-up of 33.6 months, 31 of whom took 10 mg and 34 who used 20 mg. Each group maintained up until the final visit a significant statistical improvement in erectile function, sexual satisfaction, overall satisfaction and percentages of “yes” responses to the SEP2–3 compared with baseline using the Wilcoxon test (P &lt; 0.05).

Conclusion
Tadalafil represents an effective and safe long-term option for SCI patients with ED.
Use of Penile Extender Device in the Treatment of Penile Curvature as a Result of Peyronie’s Disease. Results of a Phase II Prospective Study
Authors: Gontero Paolo , Di Marco Massimiliano , Giubilei Gianluca , Bartoletti Riccardo , Pappagallo Giovanni , Tizzani Alessandro , Mondaini Nicola 
Published: December 2008

ABSTRACT

Introduction
Pilot experiences have suggested that tension forces exerted by a penile extender may reduce penile curvature as a result of Peyronie’s disease.

Aim
To test this hypothesis in a Phase II study using a commonly marketed brand of penile extender.

Methods
Peyronie’s disease patients with a curvature not exceeding 50° with mild or no erectile dysfunction (ED) were eligible. Fifteen patients were required to test the efficacy of the device assuming an effect size of &gt;0.8, consistent with an “important” reduction in penile curvature. Changes in penile length over baseline and erectile function (EF) domain scores of the International Index of Erectile Function (IIEF) constituted secondary end points.

Main Outcome Measures
Patients were counselled on the use of the penile extender for at least 5 hours per day for 6 months. Photographic pictures of the erect penis and measurements were carried out at baseline, at 1, 3, 6, and 12 months (end of study). The IIEF-EF domain scores were administered at baseline and at the end of study. Treatment satisfaction was assessed at end of study using a nonvalidated institutional 5-item questionnaire.

Results
Penile curvature decreased from an average of 31° to 27° at 6 months without reaching the effect size (P = 0.056). Mean stretched and flaccid penile length increased by 1.3 and 0.83 cm, respectively at 6 months. Results were maintained at 12 months. Overall treatment results were subjectively scored as acceptable in spite of curvature improvements, which varied from “no change” to “mild improvement.”

Conclusions
In our study, the use of a penile extender device provided only minimal improvements in penile curvature but a reasonable level of patient satisfaction, probably attributable to increased penile length. The selection of patients with a stabilized disease, a penile curvature not exceeding 50°, and no severe ED may have led to outcomes underestimating the potential efficacy of the treatment.
Allocating emission allowances: towards a sustainable approach
Authors: Fries Steven 
Published: December 2008

Abstract:The paper examines a politically sensitive issue in design of emission allowance trading systems – how to allocate initially the allowances. In most systems, whether they cover greenhouse gases (GHG) or other pollutants, initial allowance allocations have been largely free and based on past emissions. An alternative is to allocate allowances by auctioning. Political economy considerations point to greater future use of auctioning. This paper sets out reasons for this conclusion, while arguing for a phased transition towards greater auctioning.
The EU Emissions Trading Scheme: assessment and outlook
Authors: Walker Sébastien E. J. 
Published: December 2008

Abstract:In this article I assess the design of the EU Emissions Trading Scheme and the performance of its first Phase. The article argues that, contrary to common belief, Phase I fulfilled its objectives. It then discusses the changes that have been made to the Scheme's framework for Phase II, and those that are planned for Phase III, covering the latest developments and the recent price trends for emissions allowances. I conclude that the aforementioned changes constitute substantial improvements to the Scheme, while unwelcome uncertainties nevertheless remain over long‐term price signals.
Evaluation of a Screening Test for Detection of
Giardia
and
Cryptosporidium
Parasites
Authors: Youn Sojin , Kabir Mamun , Haque Rashidul , Petri William A. 
Published: December 2008

ABSTRACT

The
Giardia/Cryptosporidium Chek
test (TechLab, Inc.), a screening test for
Giardia
and
Cryptosporidium
, was evaluated with 136 fecal samples. Using the results of the
Giardia II
test and
Cryptosporidium II
test as gold standards, it was 98.4% sensitive and 100% specific and had positive and negative predictive values of 98.7% and 99.3%.
Novel Influenza Virus NS1 Antagonists Block Replication and Restore Innate Immune Function
Authors: Basu Dipanwita , Walkiewicz Marcin P. , Frieman Matthew , Baric Ralph S. , Auble David T. , Engel Daniel A. 
Published: December 2008

ABSTRACT
The innate immune system guards against virus infection through a variety of mechanisms including mobilization of the host interferon system, which attacks viral products mainly at a posttranscriptional level. The influenza virus NS1 protein is a multifunctional facilitator of virus replication, one of whose actions is to antagonize the interferon response. Since NS1 is required for efficient virus replication, it was reasoned that chemical inhibitors of this protein could be used to further understand virus-host interactions and also serve as potential new antiviral agents. A yeast-based assay was developed to identify compounds that phenotypically suppress NS1 function. Several such compounds exhibited significant activity specifically against influenza A virus in cell culture but had no effect on the replication of another RNA virus, respiratory syncytial virus. Interestingly, cells lacking an interferon response were drug resistant, suggesting that the compounds block interactions between NS1 and the interferon system. Accordingly, the compounds reversed the inhibition of beta interferon mRNA induction during infection, which is known to be caused by NS1. In addition, the compounds blocked the ability of NS1 protein to inhibit double-stranded RNA-dependent activation of a transfected beta interferon promoter construct. The effects of the compounds were specific to NS1, because they had no effect on the ability of the severe acute respiratory syndrome coronavirus papainlike protease protein to block beta interferon promoter activation. These data demonstrate that the function of NS1 can be modulated by chemical inhibitors and that such inhibitors will be useful as probes of biological function and as starting points for clinical drug development.
Deletion of Nonstructural Proteins NS1 and NS2 from Pneumonia Virus of Mice Attenuates Viral Replication and Reduces Pulmonary Cytokine Expression and Disease
Authors: Buchholz Ursula J. , Ward Jerrold M. , Lamirande Elaine W. , Heinze Britta , Krempl Christine D. , Collins Peter L. 
Published: December 2008

ABSTRACT
Pneumonia virus of mice (PVM) strain 15 causes fatal pneumonia in mice and provides a convenient model for human respiratory syncytial virus pathogenesis and immunobiology. We prepared PVM mutants lacking the genes for nonstructural proteins NS1 and/or NS2. In Vero cells, which lack type I interferon (IFN), deletion of these proteins had no effect on the efficiency of virus growth. In IFN-competent mouse embryo fibroblasts, wild-type (wt) PVM and the ΔNS1 virus grew efficiently and strongly inhibited the IFN response, whereas virus lacking NS2 was highly attenuated and induced high levels of IFN and IFN-inducible genes. In BALB/c mice, intranasal infection with wt PVM caused overt disease that began on day 6 and was lethal by day 9 postinoculation. In comparison, ΔNS1 induced transient, reduced disease, and ΔNS2 and ΔNS12 caused no disease. Thus, NS1 and NS2 are virulence factors, with NS2 being a major antagonist of the type I IFN system. The pulmonary titers of wt PVM and ΔNS1 were high on day 3 and increased further by day 6; in addition, expression of IFN and representative proinflammatory cytokines/chemokines and T lymphocyte-related cytokines was undetectable on day 3 but increased dramatically by day 6 coincident with the onset of disease. The titers of ΔNS2 and ΔNS12 were somewhat lower on day 3 and decreased further by day 6; in addition, these viruses induced a more circumscribed set of cytokines/chemokines (IFN, interleukin-6 [IL-6], and CXCL10) that were detected on day 3 and had largely subsided by day 6. Lung immunohistology revealed abundant PVM-positive pneumocytes and bronchial and bronchiolar epithelial cells in wt PVM- and ΔNS1-infected mice on day 6 compared to few PVM-positive foci with ΔNS2 and ΔNS12. These results indicate that severe PVM disease is associated with high, poorly controlled virus replication driving the expression of high levels of pulmonary IFN and a broad array of cytokines/chemokines. In contrast, in the absence of NS2, there was an early, transient innate response involving moderate levels of IFN, IL-6, and CXCL10 that restricted virus replication and prevented disease.
Impact of research on practice in the field of inspections, reviews and walkthroughs
Authors: Rombach Dieter , Ciolkowski Marcus , Jeffery Ross , Laitenberger Oliver , McGarry Frank , Shull Forrest 
Published: December 2008

Software inspections, reviews, and walkthroughs have become a standard process component in many software development domains. Maturity level 3 of the CMM-I requires establishment of peer reviews [12] and substantial sustained improvements in quality and productivity have been reported as a result of using reviews ([16], [21], [22], [27]). The NSF Impact project identifies the degree to which these industrial success cases have been instigated and improved by research in software engineering.
This research identifies that there is widespread adoption of inspections, reviews or walkthroughs but that companies do not generally exploit their full potential. However there exist sustained industrial success cases with respect to the wide-spread and measurably successful application of them. It also identifies research in software engineering that can be credibly documented as having influenced the industrial success cases. Credible documentation may exist in the form of publications or documented reports by witnesses. Due to the semi-formal nature of inspections, reviews, and walkthroughs, a specific focus is given to empirical research results as motivators for adoption. Through the examination of one detailed case study, it is shown that software engineering research has had a significant impact on practice and that the impact can be traced in this case from research to that practice. The case study chosen provides evidence of both success and failure regarding sustained application in practice.
Thus the analysis of historic impact chains of research reveals a clear impact of software engineering research on sustained industrial success for inspections, reviews and walkthroughs. More importantly, in impact chains where the empirical results have not been established, we conclude that success has not been achieved or has not been sustained.
The paper closes with (1) lessons learned for creating the sustained use and impact of semi-formal software engineering processes, (2) a request for researchers and practitioners to further consider how their work can improve the effectiveness of research and practice, and (3) a request to contribute additional success cases and impact factors to the authors database for future enhancements of this paper.
De novo induction of platelet-specific CD4+CD25+ regulatory T cells from CD4+CD25− cells in patients with idiopathic thrombocytopenic purpura
Authors: Zhang Xiao-Lin , Peng Jun , Sun Jian-Zhi , Liu Jia-Jun , Guo Cheng-Shan , Wang Zhen-Guang , Yu Yuan , Shi Yan , Qin Ping , Li Shu-Guang , Zhang Li-Ning , Hou Ming 
Published: December 2008

AbstractCD4+CD25+ regulatory T cells (Treg) play the critical role in maintenance of peripheral immune tolerance. However, the numbers of naturally occurring Treg (nTreg) that can be isolated from periphery are far too small to be clinically effective. The isolation and expansion of nTreg for treatment of autoimmune diseases encounter great difficulties. Whether autoantigen-specific Treg could be converted from CD4+CD25− T cells in patients with autoimmune diseases has not been reported. Here, we demonstrated that platelet glycoprotein (GP)–specific induced Treg (GP-iTreg) could be generated de novo from nonregulatory CD4+CD25−CD45RA+ cells in patients with idiopathic thrombocytopenic purpura and induced both antigen-specific and linked suppression. GP-iTreg mediated regulatory effects via modulating the T cell–stimulatory capacity of dendritic cells. By investigating the gene expression profile of iTreg-modulated dendritic cells, we provided a genome-wide assessment of the changes induced by antigen-specific iTreg and identified that the Toll-like receptor, Notch and transforming growth factor-β signaling pathways were related to the GP-specific tolerance, with the Toll-like receptor pathway being dominant. The findings in patients with idiopathic thrombocytopenic purpura will facilitate our understanding of the mechanisms of induction and maintenance of autoantigen-specific tolerance and highlight the considerable potential of antigen-specific iTreg for targeted immunotherapy in human auto-immune diseases.
Detecting coevolution without phylogenetic trees? Tree-ignorant metrics of coevolution perform as well as tree-aware metrics
Authors: Caporaso J Gregory , Smit Sandra , Easton Brett C , Hunter Lawrence , Huttley Gavin A , Knight Rob 
Published: December 2008

Abstract

Background
Identifying coevolving positions in protein sequences has myriad applications, ranging from understanding and predicting the structure of single molecules to generating proteome-wide predictions of interactions. Algorithms for detecting coevolving positions can be classified into two categories: tree-aware, which incorporate knowledge of phylogeny, and tree-ignorant, which do not. Tree-ignorant methods are frequently orders of magnitude faster, but are widely held to be insufficiently accurate because of a confounding of shared ancestry with coevolution. We conjectured that by using a null distribution that appropriately controls for the shared-ancestry signal, tree-ignorant methods would exhibit equivalent statistical power to tree-aware methods. Using a novel t-test transformation of coevolution metrics, we systematically compared four tree-aware and five tree-ignorant coevolution algorithms, applying them to myoglobin and myosin. We further considered the influence of sequence recoding using reduced-state amino acid alphabets, a common tactic employed in coevolutionary analyses to improve both statistical and computational performance.

Results
Consistent with our conjecture, the transformed tree-ignorant metrics (particularly Mutual Information) often outperformed the tree-aware metrics. Our examination of the effect of recoding suggested that charge-based alphabets were generally superior for identifying the stabilizing interactions in alpha helices. Performance was not always improved by recoding however, indicating that the choice of alphabet is critical.

Conclusion
The results suggest that t-test transformation of tree-ignorant metrics can be sufficient to control for patterns arising from shared ancestry.
A toolbox for epitope-tagging and genome-wide location analysis in Candida albicans
Authors: Lavoie Hugo , Sellam Adnane , Askew Christopher , Nantel André , Whiteway Malcolm 
Published: December 2008

Abstract

Background

Candida albicans is a diploid pathogenic fungus not yet amenable to routine genetic investigations. Understanding aspects of the regulation of its biological functions and the assembly of its protein complexes would lead to further insight into the biology of this common disease-causing microbial agent.

Results
We have developed a toolbox allowing in vivo protein tagging by PCR-mediated homologous recombination with TAP, HA and MYC tags. The transformation cassettes were designed to accommodate a common set of integration primers. The tagged proteins can be used to perform tandem affinity purification (TAP) or chromatin immunoprecipitation coupled with microarray analysis (ChIP-CHIP). Tandem affinity purification of C. albicans Nop1 revealed the high conservation of the small processome composition in yeasts. Data obtained with in vivo TAP-tagged Tbf1, Cbf1 and Mcm1 recapitulates previously published genome-wide location profiling by ChIP-CHIP. We also designed a new reporter system for in vivo analysis of transcriptional activity of gene loci in C. albicans.

Conclusion
This toolbox provides a basic setup to perform purification of protein complexes and increase the number of annotated transcriptional regulators and genetic circuits in C. albicans.
Physiological and pathological aspects of Aβ in iron homeostasis via 5'UTR in the APP mRNA and the therapeutic use of iron-chelators
Authors: Avramovich-Tirosh Yael , Amit Tamar , Bar-Am Orit , Weinreb Orly , Youdim Moussa BH 
Published: December 2008

Abstract
Many studies have highlighted the pathological involvement of iron accumulation and iron-related oxidative stress (OS) in Alzheimer's disease (AD). Iron was further demonstrated to modulate expression of the Alzheimer's amyloid precursor holo-protein (APP) by a mechanism similar to that of regulation of ferritin-L and -H mRNA translation through an iron-responsive element (IRE) in their 5' untranslated regions (UTRs). Here, we discuss two aspects of the link between iron and AD, in relation to the recently discovered IRE in the 5'UTR of APP mRNA. The first is the physiological aspect: a compensatory neuroprotective response of amyloid-β protein (Aβ) in reducing iron-induced neurotoxicity. Thus, given that Aβ possesses iron chelation sites, it is hypothesized that OS-induced intracellular iron may stimulate APP holo-protein translation (via the APP 5'UTR) and subsequently the generation of its cleavage product, Aβ, as a compensatory response that eventually reduces OS. The second is the pathological aspect: iron chelating compounds target the APP 5'UTR and possess the capacity to reduce APP translation, and subsequently Aβ levels, and thus represent molecules with high potential in the development of drugs for the treatment of AD.