bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventilator‐Associated Pneumonia Bundled Strategies: An Evidence‐Based Practice
Authors: O'Keefe‐McCarthy Sheila , Santiago Cecilia , Lau Gemma
Published: December 2008

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

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 < 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

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 >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

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

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.
A Bubble Dynamics Based Approach to the Simulation of Cavitation in Lubricated Contacts
Authors: Geike Thomas , Popov Valentin L.
Published: December 2008

The negative squeeze lubrication problem is investigated by means of numerical simulations that account for the dynamics of vaporization. The model is based on bubble dynamics, governed by the Rayleigh–Plesset equation, and the Reynolds equation for compressible fluids. Unlike most existing simulation models our model can predict tensile stresses in the fluid film prior to its rupture, which is in accordance with experimental evidence.
Quantification of breast density with dual energy mammography: A simulation study
Authors: Ducote Justin L. , Molloi Sabee
Published: December 2008

Breast density, the percentage of glandular breast tissue, has been identified as an important yet underutilized risk factor in the development of breast cancer. A quantitative method to measure breast density with dual energy imaging was investigated using a computer simulation model. Two configurations to measure breast density were evaluated: the usage of monoenergetic beams and an ideal detector, and the usage of polyenergetic beams with spectra from a tungsten anode x‐ray tube with a detector modeled after a digital mammography system. The simulation model calculated the mean glandular dose necessary to quantify the variability of breast density to within . The breast was modeled as a semicircle in radius with equal homogenous thicknesses of adipose and glandular tissues. Breast thicknesses were considered in the range of 2–10 cm and energies in the range of 10–150 keV for the two monoenergetic beams, and 20–150 kVp for spectra with a tungsten anode x‐ray tube. For a 4.2 cm breast thickness, the required mean glandular doses were for two monoenergetic beams at 19 and 71 keV, and for two polyenergetic spectra from a tungsten anode at 32 and 96 kVp with beam filtrations of Rh and Cu for the low and high energy beams, respectively. The results suggest that for either configuration, breast density can be precisely measured with dual energy imaging requiring only a small amount of additional dose to the breast. The possibility of using a standard screening mammogram as the low energy image is also discussed.
Automatic segmentation of the facial nerve and chorda tympani in CT images using spatially dependent feature values
Authors: Noble Jack H. , Warren Frank M. , Labadie Robert F. , Dawant Benoit M.
Published: December 2008

In cochlear implant surgery, an electrode array is permanently implanted in the cochlea to stimulate the auditory nerve and allow deaf people to hear. A minimally invasive surgical technique has recently been proposed—percutaneous cochlear access—in which a single hole is drilled from the skull surface to the cochlea. For the method to be feasible, a safe and effective drilling trajectory must be determined using a preoperative CT. Segmentation of the structures of the ear would improve trajectory planning safety and efficiency and enable the possibility of automated planning. Two important structures of the ear, the facial nerve and the chorda tympani, are difficult to segment with traditional methods because of their size (diameters as small as 1.0 and , respectively), the lack of contrast with adjacent structures, and large interpatient variations. A multipart, model‐based segmentation algorithm is presented in this article that accomplishes automatic segmentation of the facial nerve and chorda tympani. Segmentation results are presented for ten test ears and are compared to manually segmented surfaces. The results show that the maximum error in structure wall localization is voxels for the facial nerve and the chorda, demonstrating that the method the authors propose is robust and accurate.
Objective assessment of deformable image registration in radiotherapy: A multi‐institution study
Authors: Kashani Rojano , Hub Martina , Balter James M. , Kessler Marc L. , Dong Lei , Zhang Lifei , Xing Lei , Xie Yaoqin , Hawkes David , Schnabel Julia A. , McClelland Jamie , Joshi Sarang , Chen Quan , Lu Weiguo
Published: December 2008

The looming potential of deformable alignment tools to play an integral role in adaptive radiotherapy suggests a need for objective assessment of these complex algorithms. Previous studies in this area are based on the ability of alignment to reproduce analytically generated deformations applied to sample image data, or use of contours or bifurcations as ground truth for evaluation of alignment accuracy. In this study, a deformable phantom was embedded with 48 small plastic markers, placed in regions varying from high contrast to roughly uniform regional intensity, and small to large regional discontinuities in movement. CT volumes of this phantom were acquired at different deformation states. After manual localization of marker coordinates, images were edited to remove the markers. The resulting image volumes were sent to five collaborating institutions, each of which has developed previously published deformable alignment tools routinely in use. Alignments were done, and applied to the list of reference coordinates at the inhale state. The transformed coordinates were compared to the actual marker locations at exhale. A total of eight alignment techniques were tested from the six institutions. All algorithms performed generally well, as compared to previous publications. Average errors in predicted location ranged from , depending on technique. No algorithm was uniformly accurate across all regions of the phantom, with maximum errors ranging from . Larger errors were seen in regions near significant shape changes, as well as areas with uniform contrast but large local motion discontinuity. Although reasonable accuracy was achieved overall, the variation of error in different regions suggests caution in globally accepting the results from deformable alignment.
Dosimetric characterization of a brachytherapy source by thermoluminescence dosimetry in liquid water
Authors: Tailor Ramesh , Ibbott Geoffrey , Lampe Stephanie , Bivens Warren Whitney , Tolani Naresh
Published: December 2008

Dosimetry measurements of a brachytherapy source have been performed in liquid water employing thermoluminescence dosimeters. A search of the literature reveals that this is the first time a complete set of dosimetric parameters for a brachytherapy “seed” source has been measured in liquid water. This method avoids the medium correction uncertainties introduced by the use of water‐equivalent plastic phantoms. To assure confidence in the results, four different sources were employed for each parameter measured, and measurements were performed multiple times. The measured dosimetric parameters presented here are based on the AAPM Task Group 43 formalism. The dose‐rate constant measured in liquid water was and was based on the air‐kerma strength standard for this source established by the National Institute of Standards and Technology. Measured values for the 2D anisotropy function and the radial dose function are presented.
Optimization of super‐resolution processing using incomplete image sets in PET imaging
Authors: Chang Guoping , Pan Tinsu , Clark John W. , Mawlawi Osama R.
Published: December 2008

Super‐resolution (SR) techniques are used in PET imaging to generate a high‐resolution image by combining multiple low‐resolution images that have been acquired from different points of view (POVs). The number of low‐resolution images used defines the processing time and memory storage necessary to generate the SR image. In this paper, the authors propose two optimized SR implementations (ISR‐1 and ISR‐2) that require only a subset of the low‐resolution images (two sides and diagonal of the image matrix, respectively), thereby reducing the overall processing time and memory storage. In an matrix of low‐resolution images, ISR‐1 would be generated using images from the two sides of the matrix, while ISR‐2 would be generated from images across the diagonal of the image matrix. The objective of this paper is to investigate whether the two proposed SR methods can achieve similar performance in contrast and signal‐to‐noise ratio (SNR) as the SR image generated from a complete set of low‐resolution images (CSR) using simulation and experimental studies. A simulation, a point source, and a NEMA/IEC phantom study were conducted for this investigation. In each study, 4 or 16 low‐resolution images were reconstructed from the same acquired data set while shifting the reconstruction grid to generate images from different POVs. SR processing was then applied in each study to combine all as well as two different subsets of the low‐resolution images to generate the CSR, ISR‐1, and ISR‐2 images, respectively. For reference purpose, a native reconstruction (NR) image using the same matrix size as the three SR images was also generated. The resultant images (CSR, ISR‐1, ISR‐2, and NR) were then analyzed using visual inspection, line profiles, SNR plots, and background noise spectra. The simulation study showed that the contrast and the SNR difference between the two ISR images and the CSR image were on average 0.4% and 0.3%, respectively. Line profiles of the point source study showed that the three SR images exhibited similar signal amplitudes and FWHM. The NEMA/IEC study showed that the average difference in SNR among the three SR images was 2.1% with respect to one another and they contained similar noise structure. ISR‐1 and ISR‐2 can be used to replace CSR, thereby reducing the total SR processing time and memory storage while maintaining similar contrast, resolution, SNR, and noise structure.
Dynamic Analyses of
Drosophila
Gastrulation Provide Insights into Collective Cell Migration
Authors: McMahon Amy , Supatto Willy , Fraser Scott E. , Stathopoulos Angelike
Published: December 2008

The concerted movement of cells from different germ layers contributes to morphogenesis during early embryonic development. Using an optimized imaging approach and quantitative methods, we analyzed the trajectories of hundreds of ectodermal cells and internalized mesodermal cells within
Drosophila
embryos over 2 hours during gastrulation. We found a high level of cellular organization, with mesoderm cell movements correlating with some but not all ectoderm movements. During migration, the mesoderm population underwent two ordered waves of cell division and synchronous cell intercalation, and cells at the leading edge stably maintained position. Fibroblast growth factor (FGF) signaling guides mesodermal cell migration; however, we found some directed dorsal migration in an FGF receptor mutant, which suggests that additional signals are involved. Thus, decomposing complex cellular movements can provide detailed insights into collective cell migration.
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

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

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

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.
An overview of the epidermal growth factor receptor fluorescence in situ hybridisation challenge in tumour pathology
Authors: Martin V , Mazzucchelli L , Frattini M
Published: December 2008

Epidermal growth factor receptor (EGFR) is deregulated in a variety of solid malignant tumours. Due to the availability of specific targeted therapies, the request to evaluate EGFR in neoplastic tissues in pathology is dramatically increasing. In analogy to HER2, EGFR evaluation by FISH seems to be superior than immunohistochemistry to select patients for targeted therapies. However, the lack of consensus on how to assess the presence and extent of EGFR gene status deregulation in tissue sections has generated a confusion of inadequately defined criteria, which impairs the quality of communication in both routine patient care and research studies. The objectives of this review are: (1) to analyse methodological aspects, signals evaluation and interpretation criteria related to the detection of EGFR alterations by FISH in cancer samples, highlighting technical limits and controversies; (2) to review the literature concerning EGFR FISH on formalin-fixed paraffin-embedded tissue sections from different types of solid tumours, with a particular focus on the clinical significance of numerical EGFR gene alterations with respect to targeted therapies. Further advances in improving the quality of care of patients with cancers characterised by EGFR gene deregulation will depend on answering some of the questions underlined throughout this overview.
WAVELENGTH SELECTIVE BOLOMETER DESIGN
Authors: HAN SANGWOOK , JUNG JOO-YUN , NEIKIRK DEAN P.
Published: December 2008

Multi-color narrow-band Salisbury Screen and Jaumann Absorbers combined with optimized thick Si 3 N 4 support layers are designed for wavelength selectivity in 7~14µm wavelength band. The Jaumann Absorbers are adopted as a vertically ‘stacked’ pixel structure to save space and enhance resolution compared against ‘tiled’ structure (pixels lying in a common plane).
PRECISION MEASUREMENT OF ATMOSPHERIC TRACE CONSTITUENTS USING A COMPACT FABRY-PEROT RADIOMETER
Authors: HEAPS WILLIAM S. , WILSON EMILY L. , GEORGIEVA ELENA M.
Published: December 2008

To address the problem of sources and sinks of atmospheric CO 2, measurements are needed on a global scale. Satellite instruments show promise, but typically measure the total column. Since sources and sinks at the surface represent a small perturbation to the total column, a precision of better than 1% is required. No species has ever been measured from space at this level. Over the last three years, we have developed a small instrument based upon a Fabry-Perot interferometer that is highly sensitive to atmospheric CO 2. We have tested this instrument in a ground based configuration and from aircraft platforms simulating operation from a satellite. The instrument is characterized by high signal to noise ratio, fast response and great specificity. We have performed simulations and instrument designs for systems to detect, H 2 O , CO , 13 CO 2, CH 4, CH 2 O , NH 3, SO 2, N 2 O , NO 2, and O 3. The high resolution and throughput, and small size of this instrument make it adaptable to many other atmospheric species. We present results and discuss ways this instrument can be used for ground, aircraft or space based surveillance and the detection of pollutants, toxics and industrial effluents in a variety of scenarios including battlefields, industrial monitoring, or pollution transport.
ESTIMATING THE LIMIT OF BIO-AEROSOL DETECTION WITH PASSIVE INFRARED SPECTROSCOPY
Authors: IFARRAGUERRI AGUSTIN , BEN-DAVID AVISHAI , VANDERBEEK RICHARD G.
Published: December 2008

To investigate the detection limits of biological aerosols using passive infrared measurements, we have developed a computational model that relies on physics-based simulations to generate a statistical sample. The simulation consists of three principal models: an atmospheric turbulence model, a radiative transfer model and a target detection model. The turbulence model is used to generate microscale atmospheric variability. Resulting temperature and density profiles, along with custom aerosol profiles, are used to generate inputs for MODTRAN5, which produces simulated atmospheric spectral radiance. The simulated data is then analyzed by using an optimal detection algorithm and a hypothesis test, resulting in receiver operating characteristic (ROC) curves.
EXISTENCE OF PERIODIC SOLUTIONS FOR A FREE BOUNDARY PROBLEM OF HYPERBOLIC TYPE
Authors: NAKANE KAZUAKI , SHINOHARA TOMOKO
Published: December 2008

A free boundary problem that arises from the physical phenomenon of "peeling a thin tape from a domain" is treated. In this phenomenon, the movement of the tape is governed by a hyperbolic equation and is affected by the peeling front. We are interested in the behavior of the peeling front, especially, the phenomenon of self-excitation vibration. In the present paper, a mathematical model of this phenomenon is proposed. The cause of this vibration is discussed in terms of adhesion.
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.
Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells
Authors: Sundivakkam Premanand C. , Kwiatek Angela M. , Sharma Tiffany T. , Minshall Richard D. , Malik Asrar B. , Tiruppathi Chinnaswamy
Published: December 2008

Caveolin-1 (Cav-1) regulates agonist-induced Ca2+ entry in endothelial cells; however, how Cav-1 regulates this process is poorly understood. Here, we describe that Cav-1 scaffold domain (NH2-terminal residues 82–101; CSD) interacts with transient receptor potential canonical channel 1 (TRPC1) and inositol 1,4,5-trisphosphate receptor 3 (IP3R3) to regulate Ca2+ entry. We have shown previously that the TRPC1 COOH-terminal residues 781-789 bind to CSD. In the present study, we show that the TRPC1 COOH-terminal residues 781-789 truncated (TRPC1-CΔ781-789) mutant expression abolished Ca2+ store release-induced Ca2+ influx in human dermal microvascular endothelial cell line (HMEC) and human embryonic kidney (HEK-293) cells. To understand the basis of loss of Ca2+ influx, we determined TRPC1 binding to IP3R3. We observed that the wild-type (WT)-TRPC1 but not TRPC1-CΔ781-789 effectively interacted with IP3R3. Similarly, WT-TRPC1 interacted with Cav-1, whereas TRPC1-CΔ781-789 binding to Cav-1 was markedly suppressed. We also assessed the direct binding of Cav-1 with TRPC1 and observed that the WT-Cav-1 but not the Cav-1ΔCSD effectively interacted with TRPC1. Since the interaction between TRPC1 and Cav-1ΔCSD was reduced, we measured Ca2+ store release-induced Ca2+ influx in Cav-1ΔCSD-transfected cells. Surprisingly, Cav-1ΔCSD expression showed a gain-of-function in Ca2+ entry in HMEC and HEK-293 cells. We observed a similar gain-of-function in Ca2+ entry when Cav-1ΔCSD was expressed in lung endothelial cells of Cav-1 knockout mice. Immunoprecipitation results revealed that WT-Cav-1 but not Cav-1ΔCSD interacted with IP3R3. Furthermore, we observed using confocal imaging the colocalization of IP3R3 with WT-Cav-1 but not with Cav-1ΔCSD on Ca2+ store release in endothelial cells. These findings suggest that CSD interacts with TRPC1 and IP3R3 and thereby regulates Ca2+ store release-induced Ca2+ entry in endothelial cells.
Vasopressin regulation of the renal UT-A3 urea transporter
Authors: Stewart G. S. , Thistlethwaite A. , Lees H. , Cooper G. J. , Smith Craig
Published: December 2008

Facilitative urea transporters in the mammalian kidney play a vital role in the urinary concentrating mechanism. The urea transporters located in the renal inner medullary collecting duct, namely UT-A1 and UT-A3, are acutely regulated by the antidiuretic hormone vasopressin. In this study, we investigated the vasopressin regulation of the basolateral urea transporter UT-A3 using an MDCK-mUT-A3 cell line. Within 10 min, vasopressin stimulates urea flux through UT-A3 transporters already present at the plasma membrane, via a PKA-dependent process. Within 1 h, vasopressin significantly increases UT-A3 localization at the basolateral membrane, causing a further increase in urea transport. While the basic trafficking of UT-A3 to basolateral membranes involves both protein kinase C and calmodulin, its regulation by vasopressin specifically occurs through a casein kinase II-dependent pathway. In conclusion, this study details the effects of vasopressin on UT-A3 urea transporter function and hence its role in regulating urea permeability within the renal inner medullary collecting duct.
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

CD4+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

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

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

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.
Soft drinks and 'desire to drink' in preschoolers
Authors: Sweetman Claire , Wardle Jane , Cooke Lucy
Published: December 2008

Interest in soft drink consumption has increased following a dramatic rise in intake over recent years. Research to date has focused primarily on general trends in consumption or on understanding the mechanism by which soft drink consumption may be linked to weight gain. It is clear however that there is considerable individual variability in the extent to which soft drinks are consumed and factors potentially influencing intake have received little attention. This study examines how the Child Eating Behaviour Questionnaire (CEBQ) construct 'Desire to Drink' (DD) relates to drink consumption, preferences and BMI-SDS.

Three hundred and forty six same-sex twin children (mean age 11.2 years; s.d. 0.54; 56% female; 53% dizygotic) were weighed, measured and reported their liking for milk, water, fruit juice, fruit squash and sweetened soft drinks. Mothers reported on their child's drink consumption and completed the CEBQ.

Scores on the CEBQ DD subscale were not significantly related to child BMI-SDS in this sample. Children scoring higher on DD had higher preferences for sugar-sweetened soft drinks (p = 0.016), fruit squash (p = 0.042) and milk (p = 0.020) than children scoring lower on the scale. DD was also positively related to more frequent consumption of sugar-sweetened soft drinks (p = 0.017) and low calorie soft drinks (p = 0.003). No relationship was observed between DD scores and liking for or intake of water or 100% fruit juice.

These findings suggest that the construct desire to drink in children is related to a liking for consuming sweetened drinks, and does not appear to simply denote greater thirst or hunger. This may have important implications for the ongoing development of dietary patterns and weight status in the longer term through an increased preference for sweet things in the mouth and a failure to compensate for calories provided by drinks.
HIV-1 coreceptor usage prediction without multiple alignments: an application of string kernels
Authors: Boisvert Sébastien , Marchand Mario , Laviolette François , Corbeil Jacques
Published: December 2008

Background

Human immunodeficiency virus type 1 (HIV-1) infects cells by means of ligand-receptor interactions. This lentivirus uses the CD4 receptor in conjunction with a chemokine coreceptor, either CXCR4 or CCR5, to enter a target cell. HIV-1 is characterized by high sequence variability. Nonetheless, within this extensive variability, certain features must be conserved to define functions and phenotypes. The determination of coreceptor usage of HIV-1, from its protein envelope sequence, falls into a well-studied machine learning problem known asclassification. The support vector machine (SVM), with string kernels, has proven to be very efficient for dealing with a wide class of classification problems ranging from text categorization to protein homology detection. In this paper, we investigate how the SVM can predict HIV-1 coreceptor usage when it is equipped with an appropriate string kernel.

Results

Three string kernels were compared. Accuracies of 96.35% (CCR5) 94.80% (CXCR4) and 95.15% (CCR5 and CXCR4) were achieved with the SVM equipped with thedistant segments kernelon a test set of 1425 examples with a classifier built on a training set of 1425 examples. Our datasets are built with Los Alamos National Laboratory HIV Databases sequences. A web server is available athttp://genome.ulaval.ca/hiv-dskernel.

Conclusion

We examined string kernels that have been used successfully for protein homology detection and propose a new one that we call thedistant segments kernel. We also show how to extract the most relevant features for HIV-1 coreceptor usage. The SVM with thedistant segments kernelis currently the best method described.
Cauda equina compression in an achondroplastic dwarf. Is complex anterior and posterior surgical intervention necessary?
Authors: Sapkas George , Kateros Konstantinos , Papadakis Stamatios A , Papadakis Michael , Machairas George
Published: December 2008

We report the case of an achondroplastic dwarf who presented with partial paraplegia due to cauda equina compression. The patient had marked thoracolumbar kyphosis and spinal stenosis at L2–L3. Although only posterior decompression is recommended in the literature for the treatment of achondroplastic patients presenting with neurological problems, a staged anterior and posterior decompression and stabilization was considered necessary for the treatment of this particular patient due to the presence of kyphosis. Satisfactory clinical results were achieved and sustained for six years following this complex operation.
Orocervical foetus-in-foetu with prenatal sonographic diagnosis: a case report
Authors: Braimoh Kolawole T , Abdulkadir Adekunle Y , Balogun Rabiu O
Published: December 2008

Introduction

Foetus-in-foetu is a very rare congenital abnormality where a malformed foetus is included within the body of another foetus. Less than 200 cases have been reported with over 80% occurring in the abdomen. Only three cases of cervical foetus in foetu have been reported. The present case of giant orocervical foetus-in-foetu appears to be an index case.

Case presentation

This is a report of an extremely rare orocervical foetus-in-foetu with grotesque oddity diagnosed on prenatal ultrasonography at 35 weeks gestational age in a 28-year-old, G2P1+0, Nigerian woman who was unsure of her last menstrual date or month. The included foetus had two eyes, cranium, nose, long bones and a spine. The mother's attempts at vaginal delivery rather than the elective Caesarean delivery she was offered resulted in obstructed labour and intrauterine foetal demise.

Conclusion

Giant cervical foetus-in-foetu is extremely rare. It could result in obstructed labour if vaginal delivery is attempted.