bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial Antioxidant Administration Ameliorates the Erectile Response to PDE5 Regardless of the Extension of the Atherosclerotic Process
Authors: Vicari Enzo , La Vignera Sandro , Condorelli Rosita , Calogero Aldo Eugenio
Published: August 2009

Introduction

The lack of phosphodiesterase type 5 inhibitor effects in patients with erectile dysfunction (ED) of arterial origin may be caused by an endothelial dysfunction that causes a series of biochemical alterations leading to a reduced nitric oxide (NO) bioavailability and increased oxidative stress.

Aim

The aim of this study was to evaluate the effects of the treatment with endothelial antioxidant compounds (EAC) on the erectile response to sildenafil in patients with arterial ED already treated with sildenafil (100 mg twice a week for 8 weeks).

Mean Outcome Measures

A patient was considered responsive when the 5-item International Index of Erectile Function questionnaire score increased by >5 points.

Methods

Fifty-three patients with arterial ED, hypertension, and diabetes mellitus were randomly given, for 8 weeks, EAC (1 dose/day) and, after a wash out of 8 weeks, sildenafil (100 mg) plus EAC. The patients were divided into the following four groups: A (N=12): patients with ED alone; B (N=14): patients with ED plus atheromasic plaques and/or increased intima-media thickness of common carotid arteries; C (N=14): patients with ED plus lower limb artery abnormalities; and D (N=13): patients with ED plus carotid and lower limb artery abnormalities.

Results

The administration of EAC plus sildenafil resulted in a significantly higher number of responsive patients (N=36, 68%) compared with sildenafil alone (N=24, 45%) or EAC alone (N=17, 32%). The percentage of patients who successfully responded to the combined treatment increased in the various groups. It was 83%, 64%, 71%, and 54%, respectively, for groups A, B, C, and D. Furthermore, patients treated with EAC and sildenafil reached a successful response in a shorter length of time (3 weeks) compared with patients responsive to sildenafil (5.2 weeks) or EAC (5.7 weeks) alone.

Conclusion

EAC administration to patients with arterial ED improved the success rate to sildenafil. These data suggest that, in such patients, a combined treatment may be considered to increase bioavailable NO and to neutralize radical oxygen species, which in turn inactive NO.
Erectile Dysfunction (ED) is a Shared Sexual Concern of Couples II: Association of Female Partner Characteristics with Male Partner ED Treatment Seeking and Phosphodiesterase Type 5 Inhibitor Utilization
Authors: Fisher William A. , Eardley Ian , McCabe Marita , Sand Michael
Published: August 2009

Introduction

Erectile dysfunction (ED) is a prevalent condition that impacts on both patients and their female partners. ED may therefore be regarded as a shared sexual concern for couples. The current analysis of the Female Experience of Men’s Attitudes to Life Events and Sexuality (FEMALES) study data addresses women’s perceptions, beliefs, and attitudes concerning their partner’s ED, and whether these are associated with the likelihood of the male partner seeking medical advice and utilizing phosphodiesterase type 5 inhibitors.

Aim

The current research sought to explore the association of female partners’ perceptions of male partners’ ED and male partners’ medical consultation and treatment seeking for ED.

Methods

Questionnaires were sent to partners of men who participated in the Men’s Attitudes to Life Events and Sexuality (MALES) 2004 study, and who consented to their partner’s involvement. A modified version of the questionnaire used in the MALES study was developed for the FEMALES study, reflecting the female partner’s perspective.

Main Outcome Measure

A 65-item questionnaire assessing women’s perceptions, beliefs, and attitudes regarding various aspects of ED.

Results

Women’s perceptions of the nature and causes of their partner’s ED were significantly associated with men’s treatment seeking and utilization. Significant associations were observed between women’s level of satisfaction with the relationship before ED onset; perceptions of the impact of ED on quality of life; desire to deal with ED; attitudes to ED treatment; and the treatment-seeking behavior of the male partner. Multivariate regression analyses identified a mixture of female and male partner perceptions and attitudes that uniquely accounted for >30% of the variance in men’s ED treatment-seeking behavior and treatment utilization.

Conclusion

This study illustrates the importance of the female partner’s attitudes to ED in men’s ED treatment-seeking behavior. These findings strongly support the potential benefits of partner integration into ED consultation and treatment strategies.
The nature of law as an interpretive practice and its associated modes of inquiry
Authors: Gibbs Nathan
Published: August 2009

The paper provides a critical survey of certain methodological debates in the field of legal philosophy in order to assess their implications for legal research in general. Underpinning this survey is a concern to establish the independence and integrity of both legal practice and legal research in the light of the risks posed by preponderant forms of instrumental rationality. Thus, Brian Leiter's recent call for a ‘naturalised’ jurisprudence is criticised for the instrumentalist basis upon which he claims to privilege forms of legal research apparently ‘continuous with’ the natural and empirical social sciences. As against Leiter, it is argued that there are in fact a range of distinct but interrelated modes of legal research. In this respect, the work of HLA Hart is interpreted as an example of a distinctively theoretical mode of inquiry into law. In addition, an account of the nature of a distinctively practical mode of legal inquiry is developed from a critique of Ronald Dworkin's excessively ‘theoretical’ reading of the interpretive character of legal practice. A constitutive practical feature of both modes of inquiry is their capacity to take up a certain distance from any exclusive concern with instrumental or pragmatic action.
atetra, a new software program to analyse tetraploid microsatellite data: comparison with tetra and tetrasat
Authors: VAN PUYVELDE K. , VAN GEERT A. , TRIEST L.
Published: August 2009

Despite the importance of tetraploid species, most population genetic studies deal with diploid ones because of difficulties in analysing codominant microsatellite data in tetraploid species. We developed a new software program—atetra—which combines both the rigorous method of enumeration for small data sets and Monte Carlo simulations for large ones. We discuss the added value of atetra by comparing its precision, stability and calculation time for different population sizes with those obtained from previous software programs tetrasat and tetra. The influence of the number of simulations on the calculation stability is also investigated. atetra and tetrasat proved to be more precise when compared with tetra, which, however, remains faster. atetra has the same precision than tetrasat, but is much faster, can handle an infinite number of partial heterozygotes and calculates more genetic variables. The more user‐friendly interface of atetra reduces possible mistakes.
Significance of Wip1 overexpression in breast cancer: Strong association with hormone receptor expression and nodal metastasis
Authors: Choi Jene , Kim Mi‐Jung , Han Hye‐Sook , Gong Gyungyub , Yu Eunsil
Published: August 2009

Background and aim: Wild‐type p53‐induced phosphatase (Wip1), a serine/threonine phosphatase encoded by Ppm1d, is a protein, induced by p53 in response to DNA damage. Recently, correlation between Ppm1d amplification and erbB2 expression has been reported in breast cancers. However, in vitro experiments provide evidences suggesting a relationship between Wip1 and hormone receptor (HR) activity. The aim of the current study was to clarify the relationship between Wip1 overexpression and the expression of HR and erbB2, and to investigate the prognostic significance of Wip1 in breast cancer. Methods: Using tissue microarrays that contained 743 cases of primary invasive breast cancers, we analyzed Ppm1d copy number and examined the expression of Wip1, HRs, p53 and erbB2 by immunohistochemistry. Results:Ppm1d was amplified in 4.7% of breast cancer tumors, while Wip1 was overexpressed in 20.8%. Wip1 overexpression was associated with low nuclear grade (P= 0.032), higher expression of progesterone receptor (P= 0.001), and increased nodal metastasis (P= 0.013). No statistically significant correlations were identified among other clinicopathologic parameters. Conclusions: The close correlation between Wip1 overexpression, progesterone receptor expression and nodal metastasis suggest that Wip1 expression is closely associated with HR activity and might heighten the malignant properties of breast cancers through hormone‐mediated tumor growth and progression.
Clinicopathologic significance of survivin expression in colorectal adenocarcinoma
Authors: Na Woong , Jang Se Min , Jun Young Jin , Song Young Soo , Jang Ki‐Seok , Lee Kang Hong , Lee Kyeong Geun , Han Hong Xiu , Paik Seung Sam
Published: August 2009

Background and aim: Survivin, an antiapoptotic protein, is involved in both the control of the cell division and the inhibition of apoptosis. The regulation of apoptotic cell death may have a profound effect on the carcinogenesis and progression of colorectal cancer. This study was designed to evaluate the survivin expression in colorectal tissues and to investigate whether the survivin expression is associated with the clinicopathologic characteristics and the patient survival. Methods: Immunohistochemical analysis of survivin was performed using the tissue microarrays of 622 colorectal tissue samples from 529 colorectal adenocarcinomas, 40 normal mucosa, 34 adenomatous polyps, and 59 metastatic lymph nodes. Results: Normal colorectal mucosa were completely negative for survivin (0/40, 0%), but survivin was expressed in adenomatous polyps (8/34, 23.5%), adenocarcinomas (327/529, 61.8%), and metastatic lymph nodes (27/59, 45.8%). In the analyses between the survivin expression and clinicopathologic parameters, the survivin expression was correlated with tumor location in colon (P= 0.026), lymph node metastasis (P= 0.003) and American Joint Committee on Cancer (AJCC) stage (P= 0.040). The patient survival was significantly associated with age, histologic grade, AJCC stage, and lymphovascular invasion. On stage wise analyses of patient survival, the survivin expression was significantly correlated with overall survival (P < 0.001) and disease free survival (P < 0.001), especially in stage II colorectal adenocarcinomas. Conclusions: The results suggest that the survivin expression is a relatively frequent early event of colorectal carcinogenesis and may play an important role in the adenoma‐carcinoma transition sequence. Survivin expression provides important prognostic information and an apoptosis‐based therapeutic target in colorectal adenocarcinomas.
History of reimbursement system for routine histopathology services by the National Health Insurance in Korea
Authors: Seo Jeong‐Wook , Jang Se Jin , Kim Min Suk , Kang Chang Suk , Han Woon Sup
Published: August 2009

In January 2009, a new classification of pathology services was been launched for the reimbursement by the National Health Insurance system in Korea. Five basic types of surgical pathology services are reclassified into 13 types and their resource based relative value scores are adjusted. In this report, we summarize the history of the classification system for the reimbursement on pathology services and report the impact of the change in January 2009 on the distribution of cases and contribution on the income of the department of pathology from each class at the Seoul National University Hospital.
Reporting on Service Efforts and Accomplishments on a Whole of Government‘ Basis
Authors: Walker R. G.
Published: August 2009

The United States' Governmental Accounting Standards Board has fostered the development of reports on “service efforts and accomplishments”. The SEAs framework for classifying performance indicators and providing accompanying contextual data and interpretative commentary was adopted in New South Wales, but developed through its application on a “whole of government” basis and the adoption of distinctions between “program outcomes” and “community outcomes”. The whole‐of‐government approach has the potential to provide a more consistent track record of public‐sector performance in the face of departmental restructuring or the shifting of programs or subprograms between agencies.
The New Business of Government Budgeting: Reporting Non‐Financial Performance Information in Victoria
Authors: Carlin Tyrone , Guthrie James
Published: August 2009

Since the early 1990s the general and financial management of the Victorian public sector has been significantly transformed. This research examines and explains the content, nature and quality of non‐financial disclosures, including those related to performance indicators, through a disclosure indicator analysis of reporting practices in recent government budget papers. It reports the results of its application to the last three years' budget papers. The findings highlight the problems in the reporting of non‐financial performance indicators in the Victorian budget papers. These results indicate a significant gap between “official” expectations of the type of items required to be reported and actual budgetary reporting practices – some many years after regulation and major financial accountability reforms have taken place.
Frontiers of Non‐Financial Performance Reporting in New Zealand
Authors: Neale Ann , Pallot June
Published: August 2009

In 1989, legislation in New Zealand introduced requirements for non‐financial performance information in the public sector to be reported and audited. This paper describes the initial responses of the Institute of Chartered Accountants of New Zealand and the Audit Office to this challenge and examines their further development following a decade of experience.
A Review of New Public Financial Management Change in Australia
Authors: Guthrie J. , Parker L. , English L. M.
Published: August 2009

The Australian public sector, like many in other Western democratic countries, has in past decades undergone fundamental reform of its structure, processes and underlying ideology. Our objective is to document the key features of the transformation and the influences that appear to have been at work, and to trace changes in the continuing reform of public‐sector financial management. In doing so we focus on the emerging debates over the implementation of financial management reforms and increasing public disquiet over many aspects of these reforms. The main focus is on the national level of government in Australia; however, we also draw on state government examples.
The PSASB: The Accounting Profession in Regulatory Space
Authors: Kent Jenny
Published: August 2009

This study uses the “regulatory space” construct to examine the role of the organised accounting profession in expanding and enhancing the domain of accrual accounting to Australian public‐sector financial reporting, through the advent, operations and output of the PSASB as its participant in regulatory space. To fully understand the role of the accounting profession, its actions and impacts are placed in historical and political contexts that also give consideration to the roles of other participants in regulatory space.
Public‐Interest Arguments in Privatising Government Audit
Authors: Karan Ram
Published: August 2009

The privatisation of the state audit office of Victoria in 1996–97 engendered a widespread debate that was joined by the two main accounting bodies in Australia. Although the accounting bodies adopted divergent positions, both rationalised their arguments in terms of public interest. An analysis of this paradox shows that the accountants pursued their commercial interests through intra‐professional conflict and cooperation behind the cloak of public‐interest arguments, showing little concern for the public accountability function of public‐sector audits and reporting requirements.
Are Superannuation Disclosures in Company Financial Reports Useful?
Authors: Gallery Natalie
Published: August 2009

An analysis of superannuation disclosures in the financial reports of 120 public companies shows surprisingly frequent instances of non‐compliance with AASB 1028. This is attributed to inherent weaknesses in the mandatory disclosure requirements. Significant problems include inconsistencies in the reporting of information about hybrid superannuation funds sponsored by companies, absence of timeliness, and non‐disclosure of contribution holidays. These findings suggest that present superannuation disclosure requirements do not meet the objective of providing useful information for decision‐making.
Tsunami Swamps Aid Agency Accountability: Government Waives Requirements
Authors: ABRAHAM ANNE
Published: August 2009

Following the devastating tsunamis of 26 December 2004, Australians were eager to donate money to the relief effort. An issue for many was identifying a trustworthy agency; this could be done through direct knowledge of an organisation, or by depending on the recommendations of a source whose competence and integrity was readily accepted. The Australian government provided this external credibility to the 34 charities it listed on its official tsunami assistance website. However, an investigation of these agencies and the actual appeals conducted by them indicates that the government may have waived its normal requirements by moving away from its two accountability programs, AusAID and ACFID accreditation.
An Examination of Worldwide Assured Sustainability Reporting
Authors: MOCK THEODORE J. , STROHM CHRISTIANE , SWARTZ KEVIN M.
Published: August 2009

This paper examines a sample of 130 entities worldwide which issued assured sustainability reports between 2002 and 2004. We investigate which countries and industries are more likely to have an assurance statement, what levels of assurance are provided, and what factors affect the level of assurance provided. In particular we investigate the association between the type of assurance provider (Big 4 and Non‐Big 4)1 and the nature of the assurance service provided. Descriptive statistics show that more than half of the assured sustainability reports were issued in the European Union and that Non‐Big 4 firms assured more than 60% of the reports.
A Matter of Record: Document Management as Part of Good Corporate Governance, Risk Management and Decision‐Making
Authors: BARRETT PAT
Published: August 2009

Good governance, risk management and decision‐making are facilitated by a proactive approach to document management which includes keeping necessary records but goes beyond that in order to achieve efficient and effective organisational performance. This paper's focus is on organisational knowledge, which is increasingly facilitated by information technology, and communications to capture effectively the intelligence (broadly defined) and understanding of people within the organisation. Documentation of our knowledge assets is a major exercise in risk management and its associated control environment and essential for individual and collective accountability for performance.
Actions of antidiuretic hormone analogues on intact and nystatin‐permeabilized frog skins
Authors: Jared Silviya Rajakumari , Rao J. Prakasa , Subramani Sathya
Published: August 2009

The roles of two antidiuretic hormone analogues, namely arginine vasotocin (AVT) and lysine vasopressin (LVP), in solute transport across the ventral abdominal skin of frogs (Rana hexadactyla) were studied using voltage‐clamp methods on intact and nystatin‐permeabilized preparations. Arginine vasotocin (40 nm), the amphibian analogue of antidiuretic hormone, did not have any effect on the skin of Rana hexadactyla. However, LVP, the porcine antidiuretic hormone, increased the transepithelial potential difference (TEPD) and short‐circuit current (SCC) significantly, without affecting the slope conductance. Lysine vasopressin had no action subsequent to addition of amiloride (100 μm) on the apical side or ouabain (10 μm) on the basolateral side. Lysine vasopressin increased slope conductance in the nystatin‐permeablized skin while decreasing TEPD. Such a change was not seen in chloride‐free solutions. To elucidate the mechanism of action of LVP on intact skin, experiments were done with forskolin and a V2 receptor blocker. The effects of forskolin (10 μm) were different from those of LVP in that forskolin significantly increased SCC and conductance of the intact skin, while decreasing TEPD. The forskolin‐induced increase in conductance was not abolished by amiloride. Use of the V2 receptor blocker inhibited the effects of LVP. We conclude that AVT does not have an action on the skin of Rana hexadactyla. Lysine vasopressin enhances transepithelial sodium transport by increasing sodium–potassium pump activity, while not affecting the epithelial sodium channel conductance. Lysine vasopressin also enhances an inward‐directed conductance on the basolateral membrane, probably a chloride conductance. The action of LVP on the intact frog skin is through the V2 receptors; however, downstream signalling does not seem to be mediated by cAMP. Analysis of the electrophysiological model of frog skin with LVP allows us additionally to conclude that modulation of channel activity and not carrier‐mediated transport affects slope conductance.
Influence of arousal threshold and depth of sleep on respiratory stability in man: analysis using a mathematical model
Authors: Longobardo G. S. , Evangelisti C. J. , Cherniack N. S.
Published: August 2009

We examined the effect of arousals (shifts from sleep to wakefulness) on breathing during sleep using a mathematical model. The model consisted of a description of the fluid dynamics and mechanical properties of the upper airways and lungs, as well as a controller sensitive to arterial and brain changes in CO2, changes in arterial oxygen, and a neural input, alertness. The body was divided into multiple gas store compartments connected by the circulation. Cardiac output was constant, and cerebral blood flows were sensitive to changes in O2 and CO2 levels. Arousal was considered to occur instantaneously when afferent respiratory chemical and neural stimulation reached a threshold value, while sleep occurred when stimulation fell below that value. In the case of rigid and nearly incompressible upper airways, lowering arousal threshold decreased the stability of breathing and led to the occurrence of repeated apnoeas. In more compressible upper airways, to maintain stability, increasing arousal thresholds and decreasing elasticity were linked approximately linearly, until at low elastances arousal thresholds had no effect on stability. Increased controller gain promoted instability. The architecture of apnoeas during unstable sleep changed with the arousal threshold and decreases in elasticity. With rigid airways, apnoeas were central. With lower elastances, apnoeas were mixed even with higher arousal thresholds. With very low elastances and still higher arousal thresholds, sleep consisted totally of obstructed apnoeas. Cycle lengths shortened as the sleep architecture changed from mixed apnoeas to total obstruction. Deeper sleep also tended to promote instability by increasing plant gain. These instabilities could be countered by arousal threshold increases which were tied to deeper sleep or accumulated aroused time, or by decreased controller gains.
Heat Transfer and Pressure Drop Measurements in Constant and Converging Section Pin and Diamond Pedestal Arrays
Authors: Jaswal I. , Ames F. E.
Published: August 2009

High solidity pin and pedestal arrays are beneficial in reducing temperature gradients and distributing stress across double wall cooling channels such as trailing edge regions. In this study two high solidity (45%) cooling channel geometries were selected and tested in both constant channel height and converging channel configurations. One geometry consisted of a high solidity round pin fin array and the other geometry consisted of a rounded diamond pedestal array designed to minimize pressure drop. Heat transfer rates for both geometries were determined on a row by row basis for both the constant channel and converging channel configurations. Heat transfer and pressure drop measurements were acquired in a bench scale test rig. Reynolds numbers ranged from approximately 3000 to 60,000 for the constant channel arrays and 3500 to 100,000 for the converging arrays based on the characteristic dimension of the pin or pedestal and the local maximum average velocity across a row. The high solidity pin fin array had an axial spacing (X/D) of 1.043 and a cross channel spacing (Z/D) of 1.674. The high solidity diamond pedestal array had an axial spacing of 1.00 and a cross channel spacing of 1.93. The constant section pin fin array had a channel height to diameter of 0.95 while the constant section diamond pedestal array had a height to characteristic dimension of 0.96. The converging pin fin array had an inlet to exit convergence ratio of 2.87 over five heated rows while the converging pedestal array had an inlet to exit convergence ratio of 3.53 over seven heated rows. The constant channel height internal cooling schemes have shown that the high solidity pin fin and the rounded diamond pedestal arrays produce comparable heat transfer and array pressure drop. Both the converging channel arrays show a noticeable (5–7%) reduction in heat transfer compared with the constant height channels. Array pressure drop for the two converging geometries was found to be quite consistent.
A Thermal Model for Concentric-Tube Overfire Air Ports
Authors: Swanson Larry W. , Moyeda David K.
Published: August 2009

A quasisteady multimode heat-transfer model for boiler concentric-tube overfire air ports has been developed that predicts the effect of geometry, furnace heat source and heat sink temperatures, axial injector wall conduction, and coolant flow rate on the tube wall temperature distributions. The model imposes a radiation boundary condition at the outlet tip of the ports, which acts as a heat source. The model was validated using field data and showed that both the airflow distribution in the ports and tube diameter can be used to control the maximum tube wall temperature. This helps avoid tube overheating and thermal degradation. For nominal operating conditions, highly nonlinear axial temperature distributions were observed in both tubes near the hot outlet end of the port.
Interfacial Area Transport Equation and Implementation Into Two-Fluid Model
Authors: Ishii Mamoru , Kim Seungjin , Sun Xiaodong , Hibiki Takashi
Published: August 2009

A dynamic treatment of interfacial area concentration has been studied over the last decade by employing the interfacial area transport equation. When coupled with the two-fluid model, the interfacial area transport equation replaces the flow regime dependent correlations for interfacial area concentration and eliminates potential artificial bifurcation or numerical oscillations stemming from these static correlations. An extensive database has been established to evaluate the model under various two-phase flow conditions. These include adiabatic and heated conditions, vertical and horizontal flow orientations, round, rectangular, annulus, and 8×8 rod-bundle channel geometries, and normal-gravity and reduced-gravity conditions. Currently, a two-group interfacial area transport equation is available and applicable to comprehensive two-phase flow conditions spanning from bubbly to churn-turbulent flow regimes. A framework to couple the two-group interfacial area transport equation with the modified two-fluid model is established in view of multiphase computational fluid dynamics code applications as well as reactor system analysis code applications. The present study reviews the current state-of-the-art in the development of the interfacial area transport equation, available experimental databases, and the analytical methods to incorporate the interfacial area transport equation into the two-fluid model.
A classroom demonstration of levitation and suspension of a superconductor over a magnetic track
Authors: Strehlow C. P. , Sullivan M. C.
Published: August 2009

The suspension and levitation of superconductors by permanent magnets is a fascinating consequence of superconductivity, and a wonderful way to generate interest in low-temperature physics and electrodynamics. We present a classroom demonstration of the levitation/suspension of a superconductor over a magnetic track that maximizes the levitation/suspension time and the separation distance between the magnetic track and superconductor. The demonstration, as described, is both inexpensive and easy to construct.
Echoes from the Moon
Authors: Girlanda Luca
Published: August 2009

We report on a determination of the Earth-Moon distance, performed by students of an Italian high school, based on measurements of the time delay of the “echo” in the radio communications between NASA mission control in Houston and the Apollo astronauts on the lunar surface. By using open-source audio-editing software, the distance can be determined with a∼0.1% accuracy, allowing us to observe the effect of the eccentricity of the orbit of the Moon.
Magnetic dipoles and electric currents
Authors: Corbò Guido , Testa Massimo
Published: August 2009

We discuss several similarities and differences between the concepts of electric and magnetic dipoles. We then consider the relationship between the magnetic dipole and a current loop and show that in the limit of a pointlike circuit, their magnetic fields coincide. The presentation is accessible to undergraduate students with knowledge on the basic ideas of classical electromagnetism.
Hidden momentum, field momentum, and electromagnetic impulse
Authors: Babson David , Reynolds Stephen P. , Bjorkquist Robin , Griffiths David J.
Published: August 2009

Electromagnetic fields carry energy, momentum, and angular momentum. The momentum density, ϵ0(E×B), accounts (among other things) for the pressure of light. But even static fields can carry momentum, and this would appear to contradict a general theorem that the total momentum of a closed system is zero if its center of energy is at rest. In such cases, there must be some other (nonelectromagnetic) momenta that cancel the field momentum. What is the nature of this “hidden momentum” and what happens to it when the electromagnetic fields are turned off?
Anti-Newtonian dynamics
Authors: Sprott J. C.
Published: August 2009

This paper describes a world in which Newton’s first and second laws hold, but Newton’s third law takes the form that the forces between any two objects are equal in magnitude and direction. The dynamics for such a system exhibit curious and unfamiliar features including chaos for two bodies in two spatial dimensions.
Cotransfer of Antibiotic Resistance Genes and a

hyl
Efm

-Containing Virulence Plasmid in
Enterococcus faecium
Authors: Arias Cesar A. , Panesso Diana , Singh Kavindra V. , Rice Louis B. , Murray Barbara E.
Published: August 2009

The

hyl
Efm

gene (encoding a putative hyaluronidase) has been found almost exclusively in
Enterococcus faecium
clinical isolates, and recently, it was shown to be on a plasmid which increased the ability of
E. faecium
strains to colonize the gastrointestinal tract. In this work, the results of mating experiments between

hyl
Efm

-containing strains of
E. faecium
belonging to clonal cluster 17 and isolated in the United States and Colombia indicated that the

hyl
Efm

gene of these strains is also carried on large plasmids (>145 kb) which we showed transfer readily from clinical strains to
E. faecium
hosts. Cotransfer of resistance to vancomycin and high-level resistance (HLR) to aminoglycosides (gentamicin and streptomycin) and erythromycin was also observed. The
vanA
gene cluster and gentamicin resistance determinants were genetically linked to

hyl
Efm

, whereas
erm
(B) and
ant(6)-I
, conferring macrolide-lincosamide-streptogramin B resistance and HLR to streptomycin, respectively, were not. A

hyl
Efm

-positive transconjugant resulting from a mating between a well-characterized endocarditis strain [TX0016 (DO)] and a derivative of a fecal strain of
E. faecium
from a healthy human volunteer (TX1330RF) exhibited increased virulence in a mouse peritonitis model. These results indicate that
E. faecium
strains use a strategy which involves the recruitment into the same genetic unit of antibiotic resistance genes and determinants that increase the ability to produce disease. Our findings indicate that the acquisition of the

hyl
Efm

plasmids may explain, at least in part, the recent successful emergence of some
E. faecium
strains as nosocomial pathogens.
Examination of Potential Mechanisms To Explain the Association between Proton Pump Inhibitors and
Clostridium difficile
Infection
Authors: Nerandzic Michelle M. , Pultz Michael J. , Donskey Curtis J.
Published: August 2009

Proton pump inhibitors (PPIs) have been associated with
Clostridium difficile
infection (CDI) in several recent studies. However, other studies have not shown this association, and the mechanism by which PPIs might promote CDI has not been elucidated. We hypothesized two possible mechanisms of causation: first, by raising pH, PPIs may prevent gastric contents from killing
C. difficile
spores; second, gastric contents of PPI-treated patients may promote germination and outgrowth of
C. difficile
spores. Survival rates of spores from six different strains of
C. difficile
in acidic gastric contents were assessed using quantitative cultures on selective media. Germination and outgrowth of spores were assessed by heat shock at 80°C, phase-contrast microscopy, and ethanol shock after incubation for 24 h in the gastric contents of patients and in the gastric, small intestinal, and cecal contents of mice.
C. difficile
spores survived and remained dormant in nonbilious gastric contents with acidic pH. Germination did not occur in unmodified gastric contents of patients but did occur with the addition of taurocholic acid and amino acids. In mice, germination did not occur in gastric contents but did occur in small intestinal and cecal contents. In summary,
C. difficile
spores survived in acidic gastric contents and did not undergo germination and outgrowth in gastric contents, probably due to lack of essential germinants, such as taurocholic acid. Our results suggest that the effects of PPIs in the stomach do not contribute to the pathogenesis of CDI.
Effect of Mild and Moderate Liver Disease on the Pharmacokinetics of Isavuconazole after Intravenous and Oral Administration of a Single Dose of the Prodrug BAL8557
Authors: Schmitt-Hoffmann A. , Roos B. , Spickermann J. , Heep M. , Peterfaí É. , Edwards D. J. , Stoeckel K.
Published: August 2009

Isavuconazole is a promising new antifungal drug with favorable pharmacokinetic properties and excellent activity against a number of fungi. It is administered as a water-soluble prodrug (BAL8557) that is cleaved by plasma esterases to isavuconazole, which is eliminated primarily by hepatic metabolism. The objective of this investigation was to assess the effect of alcohol-related liver disease on the pharmacokinetics of isavuconazole. Subjects were 16 healthy individuals, 16 with mild liver impairment, and 16 with moderate liver impairment who were randomized to receive a single oral or intravenous dose of BAL8557 equivalent to 100 mg isavuconazole. Blood samples were collected for 21 days following drug administration, and plasma concentrations of isavuconazole, BAL8557, and the cleavage product BAL8728 were measured using high-pressure liquid chromatography coupled with tandem mass spectrometry. Following intravenous administration, the half-life of isavuconazole increased from 123 h for healthy volunteers to 224 h and 302 h for subjects with mild and moderate liver impairment, respectively. The systemic clearance of isavuconazole following intravenous administration decreased from 2.73 liters/h for healthy subjects to 1.43 liters/h for subjects with moderate liver impairment (47.6% decrease [
P
< 0.05]). A similar decrease (23.5%) was observed after oral administration. These results suggest that a dose adjustment may be needed when isavuconazole is used to treat fungal infections in patients with liver disease.
Antibiotic Usage and Risk of Colonization and Infection with Antibiotic-Resistant Bacteria: a Hospital Population-Based Study
Authors: Tacconelli Evelina , De Angelis Giulia , Cataldo Maria Adriana , Mantengoli Elisabetta , Spanu Teresa , Pan Angelo , Corti Giampaolo , Radice Anna , Stolzuoli Lucia , Antinori Spinello , Paradisi Franco , Carosi Giampiero , Bernabei Roberto , Antonelli Massimo , Fadda Giovanni , Rossolini Gian Maria , Cauda Roberto
Published: August 2009

Accurate assessment of risk factors for nosocomial acquisition of colonization by antibiotic-resistant bacteria (ARB) is often confounded by scarce data on antibiotic use. A 12-month, nested, multicenter cohort study was conducted. Target ARB were methicillin (meticillin)-resistant
Staphylococcus aureus
(MRSA), vancomycin-resistant enterococci (VRE), and ciprofloxacin-resistant
Pseudomonas aeruginosa
(CR-PA). Nares and rectal swabs were obtained before and after starting antibiotics. Pulsed-field gel electrophoresis was done to define genetic relatedness of the strains. Primary outcomes were (i) the mean time, in days, for acquisition of target ARB colonization in patients previously not colonized; (ii) the rate of acquisition per 1,000 antibiotic-days according to different classes of antibiotics; (iii) the rate of infection caused by the same bacteria as those previously isolated in screening samples; and (iv) the risk factors for ARB acquisition. In total, 6,245 swabs from 864 inpatients were processed. The rate of acquisition was 3%, 2%, and 1% for MRSA, VRE, and CR-PA, respectively. The rate of acquisition of ARB per 1,000 antibiotic-days was 14 for carbapenems, 9 for glycopeptides, and 6 for broad-spectrum cephalosporins and quinolones. The highest rates of acquisition were observed for carbapenems in dialyzed and diabetic patients. Four risk factors were independently associated with acquisition of target ARB: use of carbapenems, age of >70 years, hospitalization for >16 days, and human immunodeficiency virus infection. During the 30-day follow-up, 4 among 42 patients newly colonized by ARB (9%) suffered from an infection due to the same bacteria as those isolated in a previous screening sample. Colonizing and infecting strains from single patients were genotypically identical. Identifying ARB colonization early during antibiotic therapy could target a high-risk hospitalized population that may benefit from intervention to decrease the risk of subsequent nosocomial infections.
Brain Penetration of Colistin in Mice Assessed by a Novel High-Performance Liquid Chromatographic Technique
Authors: Jin Liang , Li Jian , Nation Roger L. , Nicolazzo Joseph A.
Published: August 2009

A sensitive and reliable liquid chromatographic method was developed and validated for the determination of colistin concentrations in mouse brain homogenate. With a mobile phase consisting of acetonitrile-tetrahydrofuran-water (50:25:25 [vol/vol]) at a flow rate of 1 ml/min, a linear correlation between peak area and colistin concentration was observed over the concentration range of 93.8 to 3,000 ng/g in brain tissue (
R
2
> 0.994). Intra- and interday coefficients of variation were 5.1 to 8.3% and 5.8 to 8.5%, respectively, and the recovery ranged from 85% to 94%. This assay was then utilized to determine the amount of colistin that permeated the blood-brain barrier over a 2-h period following bolus intravenous administration of colistin sulfate to mice. After a single dose of 5 mg/kg of body weight to mice, brain homogenate concentrations of colistin were very low, relative to plasma colistin concentrations, suggesting that colistin permeability across the healthy blood-brain barrier is negligible during this experimental period.
Body Weight Cutoff for Daily Dosage of Efavirenz and 60-Week Efficacy of Efavirenz-Based Regimen in Human Immunodeficiency Virus and Tuberculosis Coinfected Patients Receiving Rifampin
Authors: Manosuthi Weerawat , Sungkanuparph Somnuek , Tantanathip Preecha , Mankatitham Wiroj , Lueangniyomkul Aroon , Thongyen Supeda , Eampokarap Boonchuay , Uttayamakul Sumonmal , Suwanvattana Pawita , Kaewsaard Samroui , Ruxrungtham Kiat
Published: August 2009

Seventy-one human immunodeficiency virus-infected patients with tuberculosis who were receiving a rifampin (rifampicin)-containing regimen were initiated on treatment with efavirenz at 600 mg/day plus stavudine-lamivudine. Fasting efavirenz concentrations at 12 h after dosing (C12) were monitored. The mean ± standard deviation efavirenz C12at weeks 6 and 12 and after rifampin discontinuation were 4.5 ± 4.3, 3.8 ± 3.5, and 3.5 ± 2.7 mg/liter, respectively. High body weight was associated with a low efavirenz C12at weeks 6 and 12 (P= 0.003,r= −0.255). The efavirenz C12regression prediction line at 1 mg/liter intercepted a mean body weight of 57.5 kg.
Pharmacokinetics of Fosamprenavir plus Ritonavir in Human Immunodeficiency Virus Type 1-Infected Adult Subjects with Hepatic Impairment
Authors: Pérez-Elías María J. , Morellon María Larrousse , Ortega Enrique , Hernández-Quero José , Rodríguez-Torres Maribel , Clotet Bonaventura , Felizarta Franco , Gutiérrez Felix , Pineda Juan A. , Nichols Garrett , Lou Yu , Wire Mary Beth
Published: August 2009

The effect of hepatic impairment on fosamprenavir/ritonavir pharmacokinetics was investigated. Sixty human immunodeficiency virus type 1-infected subjects, including 13, 20, and 10 subjects with mild, moderate, and severe hepatic impairment, respectively, and a comparator group of 17 subjects with normal hepatic function, were enrolled. Subjects with normal hepatic function received fosamprenavir at 700 mg plus ritonavir at 100 mg twice daily, whereas subjects with hepatic impairment received adjusted doses in anticipation of increased exposures. For subjects with mild hepatic impairment, the studied regimen of fosamprenavir 700 mg twice daily plus ritonavir 100 mg once daily delivered 17% higher values for the maximum plasma amprenavir concentration at the steady state (Cmax), 22% higher values for the area under the plasma concentration versus time curve over the dosing interval at the steady state [AUC(0-τ)], similar values for the concentration at the end of the dosing interval (Cτ), and 114% higher unboundCτvalues. For subjects with moderate hepatic impairment, the studied dosage regimen of fosamprenavir at 300 mg twice daily plus ritonavir at 100 mg once daily delivered 27% lower plasma amprenavirCmaxvalues, 27% lower AUC(0-24)values, 57% lowerCτvalues, and 21% higher unbound amprenavirCτvalues. For subjects with severe hepatic impairment, the studied dosage regimen of fosamprenavir at 300 mg twice daily plus ritonavir at 100 mg once daily delivered 19% lower plasma amprenavirCmaxvalues, 23% lower AUC(0-24)values, 38% lowerCτvalues, and similar unbound amprenavirCτvalues. With a reduced ritonavir dosing frequency of 100 mg once daily, the plasma ritonavir AUC(0-24)values were 39% lower, similar, and 40% higher for subjects with mild, moderate, and severe hepatic impairment, respectively. The results of the study support the use of reduced fosamprenavir/ritonavir doses or dosing frequencies in the treatment of patients with hepatic impairment. No significant safety issues were identified; however, plasma amprenavir and ritonavir exposures were more variable in subjects with hepatic impairment, and those patients should be closely monitored for safety and virologic response.
Longitudinal Analysis of Raltegravir Susceptibility and Integrase Replication Capacity of Human Immunodeficiency Virus Type 1 during Virologic Failure
Authors: Fransen Signe , Karmochkine Marina , Huang Wei , Weiss Laurence , Petropoulos Christos J. , Charpentier Charlotte
Published: August 2009

We characterized the raltegravir (RAL) susceptibility and the integrase (IN)-mediated replication capacity (RC) of RAL-resistant human immunodeficiency virus type 1 from two patients experiencing virologic failure during continuous RAL salvage therapy. The following two distinct outcomes were observed: (i) the selective outgrowth of virus with high-level RAL resistance and high IN-mediated RC leading to significant viral load rebound and (ii) the selection of virus with a slight reduction in RAL susceptibility and low IN-mediated RC resulting in sustained low-level viremia.
Antimalarial Activity of Simalikalactone E, a New Quassinoid from
Quassia amara
L. (Simaroubaceae)
Authors: Cachet N. , Hoakwie F. , Bertani S. , Bourdy G. , Deharo E. , Stien D. , Houel E. , Gornitzka H. , Fillaux J. , Chevalley S. , Valentin A. , Jullian V.
Published: August 2009

We report the isolation and identification of a new quassinoid named simalikalactone E (SkE), extracted from a widely used Amazonian antimalarial remedy made out of
Quassia amara
L. (Simaroubaceae) leaves. This new molecule inhibited the growth of
Plasmodium falciparum
cultured in vitro by 50%, in the concentration range from 24 to 68 nM, independently of the strain sensitivity to chloroquine. We also showed that this compound was able to decrease gametocytemia with a 50% inhibitory concentration sevenfold lower than that of primaquine. SkE was found to be less toxic than simalikalactone D (SkD), another antimalarial quassinoid from
Q. amara
, and its cytotoxicity on mammalian cells was dependent on the cell line, displaying a good selectivity index when tested on nontumorogenic cells. In vivo, SkE inhibited murine malaria growth of
Plasmodium vinckei petteri
by 50% at 1 and 0.5 mg/kg of body weight/day, by the oral or intraperitoneal routes, respectively. The contribution of quassinoids as a source of antimalarial molecules needs therefore to be reconsidered.
Aspergillus nidulans
Protein
O
-Mannosyltransferases Play Roles in Cell Wall Integrity and Developmental Patterning
Authors: Kriangkripipat Thanyanuch , Momany Michelle
Published: August 2009

Protein
O
-mannosyltransferases (Pmts) initiate
O
-mannosyl glycan biosynthesis from Ser and Thr residues of target proteins. Fungal Pmts are divided into three subfamilies, Pmt1, -2, and -4.
Aspergillus nidulans
possesses a single representative of each Pmt subfamily,
pmtA
(subfamily 2),
pmtB
(subfamily 1), and
pmtC
(subfamily 4). In this work, we show that single Δ
pmt
mutants are viable and have unique phenotypes and that the Δ
pmtA
Δ
pmtB
double mutant is the only viable double mutant. This makes
A. nidulans
the first fungus in which all members of individual Pmt subfamilies can be deleted without loss of viability. At elevated temperatures, all
A. nidulans
Δ
pmt
mutants show cell wall-associated defects and increased sensitivity to cell wall-perturbing agents. The Δ
pmt
mutants also show defects in developmental patterning. Germ tube emergence is early in Δ
pmtA
and more frequent in Δ
pmtC
mutants than in the wild type. In Δ
pmtB
mutants, intrahyphal hyphae develop. All Δ
pmt
mutants show distinct conidiophore defects. The Δ
pmtA
strain has swollen vesicles and conidiogenous cells, the Δ
pmtB
strain has swollen conidiophore stalks, and the Δ
pmtC
strain has dramatically elongated conidiophore stalks. We also show that AN5660, an ortholog of
Saccharomyces cerevisiae
Wsc1p, is modified by PmtA and PmtC. The Δ
pmt
phenotypes at elevated temperatures, increased sensitivity to cell wall-perturbing agents and restoration to wild-type growth with osmoticum suggest that
A. nidulans
Pmts modify proteins in the cell wall integrity pathway. The altered developmental patterns in Δ
pmt
mutants suggest that
A. nidulans
Pmts modify proteins that serve as spatial cues.