bluuebunny/crossref_metadata_2025 huggingface dataset:
The User Perspective in Performance Auditing—A Case Study of Norway
Authors: Arthur Arnfrid , Rydland Lars Tore , Amundsen Kristin
Published: May 2011

The user perspective is an important contextual factor for Supreme Audit Institutions (SAIs). This article provides examples from performance audits in Norway and explores why the user perspective has become important in performance audit practices. It shows that user satisfaction can be employed as a key performance indicator of effectiveness of public services. It addresses the following questions: (a) How does performance auditing relate to the evaluation field? (b) Why is the user perspective important? (c) How can the user perspective add value in performance audits? And finally, (d) How can the user perspective in performance auditing be applied to improve public services? At the end, the article identifies some challenges and opportunities that evolve from applying a user perspective.
When citizens go against elite directions
Authors: Aaroe Lene
Published: May 2011

While much research has investigated the persuasive effects of partisan cues on citizens’ evaluations of political messages, our knowledge regarding failed persuasion is limited. It remains particularly unclear whether failed elite attempts at persuasion simply leave citizens’ attitudes unchanged or whether such attempts at persuading one segment of the electorate can actually lead to a loss of support in others. This study therefore investigates partisan cues and the occurrence of contrast effects, i.e. when the presence of an elite cue induces citizens to shift their attitudes away from the viewpoint advocated in a persuasive message. Based on data from three experiments involving two different party leader cues, I demonstrate that partisan cues can trigger contrast effects among those perceiving the party leader in question as non-likeable and those who vote for a party which is politically opposed to the source. The implications of the findings are discussed.
The archive and the processor: The internal logic of Web 2.0
Authors: Gehl Robert W.
Published: May 2011

In Web 2.0, there is a social dichotomy at work based upon and reflecting the underlying Von Neumann Architecture of computers. In the hegemonic Web 2.0 business model, users are encouraged to process digital ephemera by sharing content, making connections, ranking cultural artifacts, and producing digital content, a mode of computing I call ‘affective processing.’ The Web 2.0 business model imagines users to be a potential superprocessor. In contrast, the memory possibilities of computers are typically commanded by Web 2.0 site owners. They seek to surveil every user action, store the resulting data, protect that data via intellectual property, and mine it for profit. Users are less likely to wield control over these archives. These archives are comprised of the products of affective processing; they are archives of affect, sites of decontextualized data which can be rearranged by the site owners to construct knowledge about Web 2.0 users.
Cross-cultural divergence and convergence: With special reference to the family firm in South East Asia and China
Authors: Minkes A.L. , Foster M.J.
Published: May 2011

This article examines the role of culture in the workings of firms, especially family firms, with particular reference to Hong Kong and China, and by extension to South East Asia. The article expresses the view that while culture is a very important variable in understanding and hence facilitating crosscultural business transaction, it is only one part of the explanation for the behaviour of firms and the problems which they are often observed to experience. The argument draws on a number of case studies, some real, some allegorical, drawn from the authors' experience, which illustrate the relevance of factors which transcend national and societal factors. Other secondary data are also used to support the argument. The conclusions set out are: that it is likely that, where firms are engaged in cross-cultural dealings, they will be well advised to give careful attention to what they have in common with their business collaborators, so that the expected differences may be highlighted, but seen in proper perspective; that family firms can have a real choice between ‘family oriented’ styles of management and professionally oriented management; that, as foreign direct investment into South East Asia and China grows, such considerations will become increasingly important, as will the English language as a common meeting ground.
Succession and authority: A case study of an African family business and a clan chief
Authors: Osnes Gry
Published: May 2011

The aim of this article was to explore succession as a role phenomenon. It further explores the relationship between the succession process and authority. The usefulness of the concepts of succession systems, role history and role biography are explored and discussed. The theoretical framework is based both on a system psychodynamic perspective of role and authority in organizations, and a transitional approach. The cases are from Africa, principally a family hotel owner and a clan chief. The material was mainly gathered through interviews and observations.
Implementing State Tobacco Treatment Services
Authors: Pbert Lori , Zapka Jane , Jolicoeur Denise G. , White Mary Jo , Valentine Goins Karin , Reed George , Ockene Judith K.
Published: May 2011

This case study was conducted between 2000 and 2003 to examine the implementation of community based tobacco treatment programs funded by the Massachusetts Department of Public Health Tobacco Control Program (MTCP). Four dimensions of implementation, drawn from several models of program evaluation are explored: (a) quantity of services, (b) quality of services, (c) implementation/use of systems, and (d) sustainability. The quantity of services delivered was high, reflecting MTCP’s focus on increasing availability of services, particularly in underserved populations. The quality of physician-delivered tobacco intervention did not meet national benchmarks for delivery of all 5As (Ask, Advise, Assess, Assist, Arrange follow-up) and only about half of organizations reported routine systems for auditing tobacco use documentation. Implementation of systems to identify tobacco users and deliver tobacco treatment varied widely by community health settings, with low rates of tobacco use documentation found. Finally, in an era of greater competition for scarce prevention dollars, sustainability of services over time must be planned for from the outset, as indicated by the success of programs that sustained services by proactively and creatively incorporating tobacco treatment into their organizations. This case study can inform states’ policies in their design of tobacco treatment services in community health settings.
Efficiency of Predicting Risk in Word Reading Using Fewer, Easier Letters
Authors: Petscher Yaacov , Kim Young-Suk
Published: May 2011

Letter-name identification has been widely used as part of early screening to identify children who might be at risk for future word reading difficulty. The goal of the present study was to examine whether a reduced set of letters could have similar diagnostic accuracy rather than a full set (i.e., 26 letters) when used as a screen. First, we examined whether a hierarchical scale existed among letters by using a Mokken scale analysis. Then, we contrasted diagnostic accuracy among the 5, 10, 15, and 20 easiest letters, with all 26 letters by using receiver operating characteristic (ROC) curves and indices of sensitivity, specificity, positive predictive power, and negative predictive power. Results demonstrated that a hierarchical scale existed among items in the letter-name knowledge test. In addition, assessing students on the easiest 15 letters was not statistically distinguished from all 26 letters in diagnostic accuracy. The implications of the results for the use of a Mokken scale analysis in educational research are discussed.
Oxygenated Perfluorocarbons Protect the Intestine From the Ischemia/Reperfusion Injury in Rabbits
Authors: Ntinas Achilleas , Vrochides Dionisios , Iliadis Stavros , Papageorgiou Georgios , Alvanou-Achparaki Athanasia , Papadimitriou Dimitrios , Spiridis Charalambos , Gerasimidis Thomas
Published: May 2011

Objective: To investigate whether intraluminal administration of oxygenated perfluorocarbons (PFCs) protects the enterocyte from acute ischemia-reperfusion (I/R) injury. Materials and Methods: Twenty rabbits were divided in 4 groups: sham-operated controls (group A), acute I/R (group B), acute I/R plus infusion of oxygenated PFCs 30 minutes before ischemia (group C), and acute I/R plus infusion of oxygenated PFCs 30 minutes before reperfusion (group D). Serum creatine phosphokinase (CPK) and mucosal disaccharidase activity were examined. Intestinal biopsies were obtained for electron microscopy study. Results: Group B CPK mean values are 3495.2 ± 157.35 and 4855 ± 350.21 U/L. Group C: 2674.6 ± 265.87 and 3231 ± 232.30. Group D: 2382.2 ± 102.90 and 3217.6 ± 185.61 at 120 and 180 minutes (P < .05). At 180 minutes, maltase and sucrose values were 33.63, 51.88, 8.45, and 19.91, and 17.99, 22.87, 6.62, and 14.24 µmol/min per g for groups A, B, C, and D, respectively (P < .05). Histopathology showed the least cellular deterioration in PFC groups. Conclusion: Oxygenated PFCs protect the enterocyte during bowel I/R.
Percutaneous Balloon-Expandable Stent Graft Repair of a Ruptured Iliac Aneurysm
Authors: Cookson Daniel , Raza Zahid
Published: May 2011

Elective stent graft repair of iliac aneurysm is successful and safe. There are, however, few published data on stent grafting unstable patients with acute iliac aneurysm rupture. Iliac diameter mismatch can also present a challenge to emergency endovascular treatment. We report the treatment of an unstable patient with iliac aneurysm rupture and diameter mismatch using a percutaneous balloon-expandable polytetrafluoroethylene (PTFE) stent graft. Outcomes were satisfactory up to 12-month follow-up. Treatment of iliac aneurysm rupture using a balloon-expandable stent graft can be successful in selected patients. A percutaneous approach and targeted stent graft postdilatation enable prompt repair in the presence of diameter mismatch, facilitating emergency therapy.
Emergency Endovascular Repair of Aortocaval Fistula-A Single Center Experience
Authors: Akwei Solomon , Altaf Nishath , Tennant William , MacSweeney Shane , Braithwaite Bruce
Published: May 2011

Purpose: To review the outcomes of patients undergoing emergency endovascular repair of aortocaval fistula (ACF) secondary to abdominal aortic aneurysm (AAA). Case Report: Four consecutive patients who underwent emergency endovascular repair of ACF associated with AAA in a tertiary institution between 2002 and 2009. Of the 4 patients, 3 had initially been misdiagnosed and managed for several days by other specialists for their symptoms prior to diagnosis of their ACF. Three patients died in the early postoperative period. The fourth patient made a satisfactory postoperative recovery but subsequently required further endovascular surgery to treat a persistent type 1 endoleak. Conclusions: Our experience illustrates the importance of early diagnosis and management of ACF. Even in experienced hands, the management of spontaneous ACF associated with AAA is challenging. Endovascular surgery may still have a role in improving outcomes in these patients.
Endovascular Therapy for Hepatic Artery Stenosis and Thrombosis Following Liver Transplantation
Authors: Sabri Saher S. , Saad Wael E. A. , Schmitt Timothy M. , Turba Ulku C. , Kumer Sean C. , Park Auh-Whan , Matsumoto Alan H. , Angle John F.
Published: May 2011

Purpose: To evaluate the effectiveness of endovascular management of steno-oclusive disease in liver transplants. Methods: Retrospective review of liver transplant recipients with hepatic artery stenosis (HAS) or thrombosis (HAT) was performed. The HAS group was treated with balloon angioplasty with selective stent placement. The HAT group was treated with catheter-directed thrombolysis. Primary, unassisted, and assisted patency and graft survival rates were calculated. Results: In all, 31 patients were identified (21 males; mean age, 51 years). A total of 25 of 31 (81%) patients had HAS and 6 of 31 (19%) had HAT. Collectively, a total of 35 endovascular procedures were performed to treat HAS in 25 patients. Overall technical success rate was 91%, with 11% major complication rate. Primary-assisted patency rate and graft survival at 6 and 12 months were 87% and 81%, and 76% and 72%, respectively. Only 1 successful thrombolysis of HAT was achieved. Conclusion: Endovascular management is effective for HAS but not for HAT.
The Vascular Adventitia: Its Role in the Arterial Injury Response
Authors: Havelka George E. , Kibbe Melina R.
Published: May 2011

The belief that the adventitia serves only a structural purpose has changed over the last decade. Studies have begun to elucidate the role the adventitia plays in the arterial response to injury. The adventitial fibroblast plays an integral part in the development of neointimal hyperplasia. Adiponectin, an adipokine produced from periadventitial adipose tissue, exhibits numerous vasoprotective properties. Stem cells arise, in part, from the adventitia, and stem cell recruitment into the adventitia from the vasa vasorum has been shown to be important in the development of neointimal hyperplasia. The exact role the vasa vasorum plays in neointimal growth is poorly understood and different studies endorse conflicting viewpoints. Thus, understanding the nuances of adventitial pathophysiology will allow us to better appreciate the mechanisms behind the pathology of neointimal hyperplasia. This review will summarize recent findings on the active role the adventitia plays toward the development of neointimal hyperplasia.
Outcome of Lower Limb Distal Bypass in Afro-Caribbean Populations
Authors: Tiwari Alok , Slim Hani , Edmonds Michael , Ritter Jens Carsten , Rashid Hisham
Published: May 2011

There is little data on outcome following lower limb bypass surgery in ethnic minorities in the United Kingdom. We looked at the results of distal bypass surgery in Afro-Caribbeans (AFCs) and compared it to caucasians (CAs). Patients undergoing distal bypass between 2004 and 2009 were analyzed. Life table analyses and log rank were used to compare graft patency and amputation-free survival. A total of 86 CA and 39 AFC patients, with a median age of 78 years and 73 years, respectively (P = .01), underwent bypass. There were more women in AFC groups (41.1%) compared to CA group (19.2%, P = .01). Tissue loss as indication for surgery was more in AFC than in CA group (92.3% vs73.9%, P = .03). Primary, primary-assisted and secondary patency rates, and amputation-free survival at 12 months for AFCs compared to CAs (51.3 vs 44.6; 85.2 vs 80.9; 91.2 vs 84.4; and 84.9 vs 75.1). Graft patency after lower limb distal revascularization in AFCs is comparable to CAs.
Transradial Embolization of a Bleeding Renal Angiomyolipoma
Authors: Abrams Joseph , Yee Dominic C. , Clark Timothy W. I.
Published: May 2011

Renal angiomyolipoma (AML) is a benign neoplasm with a propensity to bleed among patients with tumors exceeding 4 cm in diameter but can be effectively treated with transarterial embolization to arrest or prevent hemorrhage. We report the use of transradial approach to embolize a bleeding AML in a pregnant patient in order to minimize pelvic radiation. This case illustrates the utility of transradial access as an access approach for performing superselective visceral embolization when a femoral approach is undesirable or not possible.
Clinical Science Review Article: Understanding the Implications of Diabetes on the Vascular System
Authors: Emond Zachary M. , Kibbe Melina R.
Published: May 2011

Patients with diabetes comprise an extremely complex subset of patients for the vascular surgeon. Often, they have numerous comorbidities that can further complicate matters. The diabetic environment is highly complex and the interplay of various diseases makes this an extremely challenging condition to manage. Knowing the mechanisms by which diabetes inflicts adverse microscopic changes in the vasculature allows the clinician to anticipate problems and minimize the heightened risks observed in diabetic patients undergoing surgery. In this review, we will illustrate how diabetes affects the vasculature and how the molecular and cellular derangements that occur in diabetic environments lead to these pathophysiologic consequences.
Treatment of Chronic Venous Stent Occlusion With a Wildcat Catheter
Authors: Smeds Matthew R. , Jacobs Donald L.
Published: May 2011

A 47-year-old female with an occluded iliac vein stent originally placed for deep venous thrombosis and May-Thurner syndrome presented to our clinic with complaints of left lower extremity pain and swelling. Multiple previous attempts had been made to cross this lesion with guidewire and catheter techniques without success. We were able to cross the lesion with the Wildcat catheter. Subsequent directional laser atherectomy and balloon angioplasty followed by stent placement resulted in a patent stent and resolution of her symptoms. This is the first reported use of the Wildcat catheter in chronic venous stent occlusions.
Spinal Cord Ischemia Following External Iliac Artery Angioplasty: A Case Report
Authors: Bani-Hani Mohamed G. , Friere Victoria , Byrne Ben E. , Plant Graham R. , Moawad Magdy R.
Published: May 2011

Spinal cord ischemia (SCI) is a rare disease that leads to variable degrees of neurological deficit including permanent paraplegia. It has been reported after open and endovascular interventions of the thoracic and abdominal aorta, but it is extremely rare after interventions involving peripheral vessels. We present a case of permanent paraplegia after iliac angioplasty and stenting for critical limb ischemia and a related review of the literature.
Pandemic Influenza A (H1N1) Infection among HIV-Infected Adults in France
Authors: Tourdjman Mathieu , Chea Sokéo , Goff Jérome Le , De Verdiere Nathalie Colin , Scemla Anne , Pavie Juliette , Simon François , Molina Jean-Michel
Published: May 2011

Clinical, biological, and radiological findings of influenza A (H1N1)-confirmed cases among HIV-infected patients presenting in a French university hospital between October 2009 and January 2010 were systematically reviewed. No severe influenza infection was observed, but a high frequency of secondary bacterial pneumonia is reported among pneumococcal unvaccinated patients.
The Struggle for Heterofeminine Recognition: Bullying, Embodiment, and Reactive Sexual Offending by Adolescent Girls
Authors: Messerschmidt James W.
Published: May 2011

No criminological research has yet examined how embodied interaction in a particular local in school, gendered milieu, may be related to engaging in sexual offenses by adolescent girls outside school boundaries. Additionally, studies of adolescent sexual offending by girls are appallingly gender and sexuality blind; no research considers the impact of both gender and sexuality on such girls. This work seeks to remedy these two crucial oversights by scrutinizing the movement from having been bullied to engaging specifically in outside-school sexual offenses, and how this social process is related specifically to embodied heterofemininities by adolescent girls.
Metabolic syndrome and exaggerated blood pressure response to exercise in newly diagnosed hypertensive patients
Authors: Tsioufis Costas , Kasiakogias Alexandros , Tsiachris Dimitris , Kordalis Athanasios , Thomopoulos Costas , Giakoumis Michalis , Bounas Pavlos , Pittaras Andreas , Michaelides Andreas , Stefanadis Christodoulos
Published: May 2011

Background: Running evidence supports a prognostic value of an exaggerated blood pressure response to exercise (EBPR). The impact of the metabolic syndrome (MS) on EBPR in hypertensive patients has not been investigated.

Design: A cross-sectional study in the setting of an outpatient hypertension clinic.

Methods: In total, 325 non-diabetic patients with newly diagnosed hypertension were divided into two groups based on the presence ( n = 95) or absence ( n = 230) of the MS as defined with NCEP-ATP III criteria. All subjects underwent ambulatory blood pressure monitoring, echocardiography and exercise treadmill testing.

Results: Hypertensive patients with MS exhibited higher prevalence of EBPR (by 17%, p = 0.002) and peak exercise systolic BP (by 10.4 mmHg, p = 0.001) irrespectively of confounders. Metabolic equivalents were higher in hypertensives with MS (by 0.6 ml/kg/min, p = 0.048), but the difference lost significance after adjusting for confounders, including body mass index. Logistic regression analysis identified the MS as an independent predictor of an EBPR ( p = 0.016). Hypertensive patients with MS had a 2.3-fold risk of exhibiting EBPR compared to those without MS. However, individual components of MS altogether as well as each one separately failed to predict EBPR.

Conclusions: Presence of MS in newly diagnosed hypertensive patients is associated with increased peak exercise BP and a higher frequency of EBPR over and above its separate elements.
Distribution of short and lifetime risks for cardiovascular disease in Italians
Authors: Di Castelnuovo Augusto , Costanzo Simona , Persichillo Mariarosaria , Olivieri Marco , de Curtis Amalia , Zito Francesco , Donati Maria Benedetta , de Gaetano Giovanni , Iacoviello Licia
Published: May 2011

Background: Guidelines for primary prevention recommend calculation of lifetime risk for cardiovascular disease (CVD) in addition to short-time risk. We aimed at evaluating the distribution of CVD lifetime risk and the percentage of Italians having low short-term, but high lifetime, risk.

Design: Cross-sectional general population-based cohort study.

Methods: We included 8,403 (46% men) cardiovascular disease-free individuals aged 35–50 years, among those randomly recruited in the framework of the MOLI-SANI cohort. Participants were stratified into three groups: low short-time (10-year) (≤3% and non diabetic)/low lifetime, low short-time/high lifetime, and high short-time risk. Short-time risk was evaluated by the equation provided by the Italian CUORE project. Lifetime risk was evaluated using the algorithm derived from the Framingham cohort.

Results: High short-time risk was prevalent in 16% population (32% of men and 2% of women). Among individuals with low short-time risk, 80% had high lifetime risk (82% men and 78% women). The proportion of individuals with very low lifetime risk due to all optimal risk factors was 4.1% only (1.5% men and 6.3% women).

Conclusions: A large proportion of Italian adults not qualified for CVD primary prevention because of their very low short-time predicted CVD risk, are in fact at high risk to develop a CVD event in their lifetime; therefore population-based approaches should be sought to modify the overall distribution of individual risk factors. These findings offer helpful information for policy makers involved in contrasting the burden of CVD, especially in women and young men.
A review of the literature relating to psychological interventions and people with intellectual disabilities: Issues for research, policy, education and clinical practice
Authors: Brown Michael , Duff Heather , Karatzias Thanos , Horsburgh Dorothy
Published: May 2011

The aim of this review is to identify and analyse the published evidence base and wider literature in relation to psychological interventions for adults with intellectual disabilities. The review suggests that the evidence base regarding psychological interventions is sparse yet growing, and if the therapeutic approaches are modified and adapted to meet the distinct needs of people with intellectual disabilities these may be life enhancing. The lack of access to psychotherapies for people with intellectual disabilities has led to their exclusion from mainstream research, thereby limiting the evidence base on effective interventions and treatment approaches. This has significant implications for research, policy, education and clinical practice and is an area requiring strategic and local attention and development in the future.
Preventing abuse in accommodation services: From procedural response to protective cultures
Authors: Robinson Sally , Chenoweth Lesley
Published: May 2011

This article reviews current approaches of disability accommodation services to addressing the abuse and neglect of people with intellectual disability who live in them. We review international literature and provide practice examples from accommodation services for people with intellectual disability in Australia to develop a framework of current research, policy and practice in this area. The results of this review show that dominant policy and practice approaches do not give adequate consideration to the prevention and protection of people from harm, focusing primarily on responding to individual instances of maltreatment. Managerial, compliance-based systems may be deflecting attention from recognizing and responding more effectively to abuse and neglect at individual, systemic and structural levels. The current dominant approach fails to develop a culture of prevention and protection for people with intellectual disability. Further, some systemic and structural preconditions are set which make abuse and neglect less likely to be prevented.
Eigenstructure assignment-based controllers applied to flexible spacecraft
Authors: Crespo J , Aranda J
Published: May 2011

The objective of this article is to evaluate the behaviour of a controller designed using a parametric eigenstructure assignment method and to evaluate its suitability for use in flexible spacecraft. The challenge of this objective lies in obtaining a suitable controller that is specifically designated to alleviate the deflections and vibrations suffered by external appendages in a flexible spacecraft while performing attitude manoeuvres. One of the main problems in these vehicles is the mechanical cross-coupling that exists between the rigid and flexible parts of the spacecraft. Spacecraft with fine attitude pointing requirements need precise control of the mechanical coupling to avoid undesired attitude misalignment. In designing an attitude controller, it is necessary to consider the possible vibration of the solar panels and how it may influence the performance of the rest of the vehicle. The nonlinear mathematical model of a flexible spacecraft is considered a close approximation to the real system. During the process of controller evaluation, the design process has also been taken into account as a factor in assessing the robustness of the system.
Development of low frequency pulse detonation engine with high-G mitigating system for aero-spacecraft propulsion
Authors: Gong ShaoWei
Published: May 2011

This research proposes a low-frequency pulse detonation engine (LPDE) with the corresponding method of anti-high- G effect. It tries to adopt the advantages of both the traditional pulse detonation engine (PDE) and the solid fuel rocket to form a new kind of engine that can use high-energy solid fuel with enclosed high-pressure explosion to generate efficient pulse propulsion. With the development, not only will the benefits of the PDE and the solid fuel rocket be greatly promoted, but the possible damage of high- G effect associated with large pulse thrust can also be prevented. As a result, it conducts the development of a cutting-edge propulsion technology that can be employed in both aeronautical and astronautical engineering. With comparison of existing propulsion technologies, the proposed LPDE technology is expected to have the characteristics of small volume, light weight, high fuel efficiency, large propulsion thrust, effective mitigation of high- G effect, and being suitable for a new generation of aero-spacecrafts to run in both low atmospheric layer and outer space. Based on theoretical analysis, the research has essentially paved the way for the realization of LPDE technology. Two examples, one in zero-gravity environment and the other in one-gravity environment, are discussed to demonstrate the significance of the research.
Discrimination of approved drugs from experimental drugs by learning methods
Authors: Tang Kailin , Zhu Ruixin , Li Yixue , Cao Zhiwei
Published: May 2011

Background

To assess whether a compound is druglike or not as early as possible is always critical in drug discovery process. There have been many efforts made to create sets of 'rules' or 'filters' which, it is hoped, will help chemists to identify 'drug-like' molecules from 'non-drug' molecules. However, among the chemical space of the druglike molecules, the minority will be approved drugs. Classifying approved drugs from experimental drugs may be more helpful to obtain future approved drugs. Therefore, discrimination of approved drugs from experimental ones has been done in this paper by analyzing the compounds in terms of existing drugs features and machine learning methods.

Results

Four methodologies were compared by their performance to classify approved drugs from experimental ones. The best results were obtained by SVM, in which the accuracy is 0.7911, the sensitivity is 0.5929, and the specificity is 0.8743. Based on the results, consensus model was developed to effectively discriminate drugs, which further pushed the correct classification rate up to 0.8517, sensitivity up to 0.7242, specificity up to 0.9352. The applications on the Traditional Chinese Medicine Ingredients Database (TCM-ID) tested the methods. Therefore this model has been proven to be a potent tool for identifying drug molecules.

Conclusion

The studies would have potential applications in the research of combinatorial library design and virtual high throughput screening for drug discovery.
Conformational and functional analysis of molecular dynamics trajectories by Self-Organising Maps
Authors: Fraccalvieri Domenico , Pandini Alessandro , Stella Fabio , Bonati Laura
Published: May 2011

Background

Molecular dynamics (MD) simulations are powerful tools to investigate the conformational dynamics of proteins that is often a critical element of their function. Identification of functionally relevant conformations is generally done clustering the large ensemble of structures that are generated. Recently, Self-Organising Maps (SOMs) were reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data mining problems. We present a novel strategy to analyse and compare conformational ensembles of protein domains using a two-level approach that combines SOMs and hierarchical clustering.

Results

The conformational dynamics of the α-spectrin SH3 protein domain and six single mutants were analysed by MD simulations. The Cα's Cartesian coordinates of conformations sampled in the essential space were used as input data vectors for SOM training, then complete linkage clustering was performed on the SOM prototype vectors. A specific protocol to optimize a SOM for structural ensembles was proposed: the optimal SOM was selected by means of a Taguchi experimental design plan applied to different data sets, and the optimal sampling rate of the MD trajectory was selected. The proposed two-level approach was applied to single trajectories of the SH3 domain independently as well as to groups of them at the same time. The results demonstrated the potential of this approach in the analysis of large ensembles of molecular structures: the possibility of producing a topological mapping of the conformational space in a simple 2D visualisation, as well as of effectively highlighting differences in the conformational dynamics directly related to biological functions.

Conclusions

The use of a two-level approach combining SOMs and hierarchical clustering for conformational analysis of structural ensembles of proteins was proposed. It can easily be extended to other study cases and to conformational ensembles from other sources.
Detection of QTL with effects on osmoregulation capacities in the rainbow trout (Oncorhynchus mykiss)
Authors: Le Bras Yvan , Dechamp Nicolas , Krieg Francine , Filangi Olivier , Guyomard René , Boussaha Mekki , Bovenhuis Henk , Pottinger Thomas G , Prunet Patrick , Le Roy Pascale , Quillet Edwige
Published: May 2011

Background

There is increasing evidence that the ability to adapt to seawater in teleost fish is modulated by genetic factors. Most studies have involved the comparison of species or strains and little is known about the genetic architecture of the trait. To address this question, we searched for QTL affecting osmoregulation capacities after transfer to saline water in a nonmigratory captive-bred population of rainbow trout.

Results

A QTL design (5 full-sib families, about 200 F2 progeny each) was produced from a cross between F0 grand-parents previously selected during two generations for a high or a low cortisol response after a standardized confinement stress. When fish were about 18 months old (near 204 g body weight), individual progeny were submitted to two successive hyper-osmotic challenges (30 ppt salinity) 14 days apart. Plasma chloride and sodium concentrations were recorded 24 h after each transfer. After the second challenge, fish were sacrificed and a gill index (weight of total gill arches corrected for body weight) was recorded. The genome scan was performed with 196 microsatellites and 85 SNP markers. Unitrait and multiple-trait QTL analyses were carried out on the whole dataset (5 families) through interval mapping methods with the QTLMap software. For post-challenge plasma ion concentrations, significant QTL (P < 0.05) were found on six different linkage groups and highly suggestive ones (P < 0.10) on two additional linkage groups. Most QTL affected concentrations of both chloride and sodium during both challenges, but some were specific to either chloride (2 QTL) or sodium (1 QTL) concentrations. Six QTL (4 significant, 2 suggestive) affecting gill index were discovered. Two were specific to the trait, while the others were also identified as QTL for post-challenge ion concentrations. Altogether, allelic effects were consistent for QTL affecting chloride and sodium concentrations but inconsistent for QTL affecting ion concentrations and gill morphology. There was no systematic lineage effect (grand-parental origin of QTL alleles) on the recorded traits.

Conclusions

For the first time, genomic loci associated with effects on major physiological components of osmotic adaptation to seawater in a nonmigratory fish were revealed. The results pave the way for further deciphering of the complex regulatory mechanisms underlying seawater adaptation and genes involved in osmoregulatory physiology in rainbow trout and other euryhaline fishes.
A sequence-based genetic linkage map as a reference for Brassica rapa pseudochromosome assembly
Authors: Wang Yan , Sun Silong , Liu Bo , Wang Hui , Deng Jie , Liao Yongcui , Wang Qian , Cheng Feng , Wang Xiaowu , Wu Jian
Published: May 2011

Background

Brassica rapa is an economically important crop and a model plant for studies concerning polyploidization and the evolution of extreme morphology. The multinational B. rapa Genome Sequencing Project (BrGSP) was launched in 2003. In 2008, next generation sequencing technology was used to sequence the B. rapa genome. Several maps concerning B. rapa pseudochromosome assembly have been published but their coverage of the genome is incomplete, anchoring approximately 73.6% of the scaffolds on to chromosomes. Therefore, a new genetic map to aid pseudochromosome assembly is required.

Results

This study concerns the construction of a reference genetic linkage map for Brassica rapa, forming the backbone for anchoring sequence scaffolds of the B. rapa genome resulting from recent sequencing efforts. One hundred and nineteen doubled haploid (DH) lines derived from microspore cultures of an F1 cross between a Chinese cabbage (B. rapa ssp. pekinensis) DH line (Z16) and a rapid cycling inbred line (L144) were used to construct the linkage map. PCR-based insertion/deletion (InDel) markers were developed by re-sequencing the two parental lines. The map comprises a total of 507 markers including 415 InDels and 92 SSRs. Alignment and orientation using SSR markers in common with existing B. rapa linkage maps allowed ten linkage groups to be identified, designated A01-A10. The total length of the linkage map was 1234.2 cM, with an average distance of 2.43 cM between adjacent marker loci. The lengths of linkage groups ranged from 71.5 cM to 188.5 cM for A08 and A09, respectively. Using the developed linkage map, 152 scaffolds were anchored on to the chromosomes, encompassing more than 82.9% of the B. rapa genome. Taken together with the previously available linkage maps, 183 scaffolds were anchored on to the chromosomes and the total coverage of the genome was 88.9%.

Conclusions

The development of this linkage map is vital for the integration of genome sequences and genetic information, and provides a useful resource for the international Brassica research community.
PNA-FISH as a new diagnostic method for the determination of clarithromycin resistance of Helicobacter pylori
Authors: Cerqueira Laura , Fernandes Ricardo M , Ferreira Rui M , Carneiro Fátima , Dinis-Ribeiro Mário , Figueiredo Céu , Keevil Charles W , Azevedo Nuno F , Vieira Maria J
Published: May 2011

Background

Triple therapy is the gold standard treatment for Helicobacter pylori eradication from the human stomach, but increased resistance to clarithromycin became the main factor of treatment failure. Until now, fastidious culturing methods are generally the method of choice to assess resistance status. In this study, a new genotypic method to detect clarithromycin resistance in clinical samples, based on fluorescent in situ hybridization (FISH) using a set of peptide nucleic acid probes (PNA), is proposed.

Results

The set of probes targeting the point mutations responsible for clarithromycin resistance was applied to H. pylori suspensions and showed 100% sensitivity and specificity (95% CI, 79.9-100 and 95% CI, 71.6-100 respectively). This method can also be amenable for application to gastric biopsy samples, as resistance to clarithromycin was also detected when histological slides were tested.

Conclusions

The optimized PNA-FISH based diagnostic method to detect H. pylori clarithromycin resistance shown to be a very sensitive and specific method for the detection of clarithromycin resistance in the H. pylori smears and also proved to be a reliable method for the diagnosis of this pathogen in clinical samples and an alternative to existing plating methods.
Sequencing and Characterization of Pseudomonas aeruginosa phage JG004
Authors: Garbe Julia , Bunk Boyke , Rohde Manfred , Schobert Max
Published: May 2011

Background

Phages could be an important alternative to antibiotics, especially for treatment of multiresistant bacteria as e.g. Pseudomonas aeruginosa. For an effective use of bacteriophages as antimicrobial agents, it is important to understand phage biology but also genes of the bacterial host essential for phage infection.

Results

We isolated and characterized a lytic Pseudomonas aeruginosa phage, named JG004, and sequenced its genome. Phage JG004 is a lipopolysaccharide specific broad-host-range phage of the Myoviridae phage family. The genome of phage JG004 encodes twelve tRNAs and is highly related to the PAK-P1 phage genome. To investigate phage biology and phage-host interactions, we used transposon mutagenesis of the P. aeruginosa host and identified P. aeruginosa genes, which are essential for phage infection. Analysis of the respective P. aeruginosa mutants revealed several characteristics, such as host receptor and possible spermidine-dependance of phage JG004.

Conclusions

Whole genome sequencing of phage JG004 in combination with identification of P. aeruginosa host genes essential for infection, allowed insights into JG004 biology, revealed possible resistance mechanisms of the host bacterium such as mutations in LPS and spermidine biosynthesis and can also be used to characterize unknown gene products in P. aeruginosa.
Cell-to-cell diversity in protein levels of a gene driven by a tetracycline inducible promoter
Authors: Smolander Olli-Pekka , Kandhavelu Meenakshisundaram , Mannerström Henrik , Lihavainen Eero , Kalaichelvan Shanmugapriya , Healy Shannon , Yli-Harja Olli , Karp Matti , Ribeiro Andre S
Published: May 2011

Background

Gene expression in Escherichia coli is regulated by several mechanisms. We measured in single cells the expression level of a single copy gene coding for green fluorescent protein (GFP), integrated into the genome and driven by a tetracycline inducible promoter, for varying induction strengths. Also, we measured the transcriptional activity of a tetracycline inducible promoter controlling the transcription of a RNA with 96 binding sites for MS2-GFP.

Results

The distribution of GFP levels in single cells is found to change significantly as induction reaches high levels, causing the Fano factor of the cells' protein levels to increase with mean level, beyond what would be expected from a Poisson-like process of RNA transcription. In agreement, the Fano factor of the cells' number of RNA molecules target for MS2-GFP follows a similar trend. The results provide evidence that the dynamics of the promoter complex formation, namely, the variability in its duration from one transcription event to the next, explains the change in the distribution of expression levels in the cell population with induction strength.

Conclusions

The results suggest that the open complex formation of the tetracycline inducible promoter, in the regime of strong induction, affects significantly the dynamics of RNA production due to the variability of its duration from one event to the next.
Bayesian adjustment for measurement error in continuous exposures in an individually matched case-control study
Authors: Espino-Hernandez Gabriela , Gustafson Paul , Burstyn Igor
Published: May 2011

Background

In epidemiological studies explanatory variables are frequently subject to measurement error. The aim of this paper is to develop a Bayesian method to correct for measurement error in multiple continuous exposures in individually matched case-control studies. This is a topic that has not been widely investigated. The new method is illustrated using data from an individually matched case-control study of the association between thyroid hormone levels during pregnancy and exposure to perfluorinated acids. The objective of the motivating study was to examine the risk of maternal hypothyroxinemia due to exposure to three perfluorinated acids measured on a continuous scale. Results from the proposed method are compared with those obtained from a naive analysis.

Methods

Using a Bayesian approach, the developed method considers a classical measurement error model for the exposures, as well as the conditional logistic regression likelihood as the disease model, together with a random-effect exposure model. Proper and diffuse prior distributions are assigned, and results from a quality control experiment are used to estimate the perfluorinated acids' measurement error variability. As a result, posterior distributions and 95% credible intervals of the odds ratios are computed. A sensitivity analysis of method's performance in this particular application with different measurement error variability was performed.

Results

The proposed Bayesian method to correct for measurement error is feasible and can be implemented using statistical software. For the study on perfluorinated acids, a comparison of the inferences which are corrected for measurement error to those which ignore it indicates that little adjustment is manifested for the level of measurement error actually exhibited in the exposures. Nevertheless, a sensitivity analysis shows that more substantial adjustments arise if larger measurement errors are assumed.

Conclusions

In individually matched case-control studies, the use of conditional logistic regression likelihood as a disease model in the presence of measurement error in multiple continuous exposures can be justified by having a random-effect exposure model. The proposed method can be successfully implemented in WinBUGS to correct individually matched case-control studies for several mismeasured continuous exposures under a classical measurement error model.
Pulmonary melioidosis in Cambodia: A prospective study
Authors: Rammaert Blandine , Beauté Julien , Borand Laurence , Hem Sopheak , Buchy Philippe , Goyet Sophie , Overtoom Rob , Angebault Cécile , Te Vantha , Try Patrich Lorn , Mayaud Charles , Vong Sirenda , Guillard Bertrand
Published: May 2011

Background

Melioidosis is a disease caused by Burkholderia pseudomallei and considered endemic in South-East Asia but remains poorly documented in Cambodia. We report the first series of hospitalized pulmonary melioidosis cases identified in Cambodia describing clinical characteristics and outcomes.

Methods

We characterized cases of acute lower respiratory infections (ALRI) that were identified through surveillance in two provincial hospitals. Severity was defined by systolic blood pressure, cardiac frequency, respiratory rate, oxygen saturation and body temperature. B. pseudomallei was detected in sputum or blood cultures and confirmed by API20NE gallery. We followed up these cases between 6 months and 2 years after hospital discharge to assess the cost-of-illness and long-term outcome.

Results

During April 2007 - January 2010, 39 ALRI cases had melioidosis, of which three aged ≤2 years; the median age was 46 years and 56.4% were males. A close contact with soil and water was identified in 30 patients (76.9%). Pneumonia was the main radiological feature (82.3%). Eleven patients were severe cases. Twenty-four (61.5%) patients died including 13 who died within 61 days after discharge. Of the deceased, 23 did not receive any antibiotics effective against B. pseudomallei. Effective drugs that were available did not include ceftazidime. Mean total illness-related costs was of US$65 (range $25-$5000). Almost two-thirds (61.5%) incurred debt and 28.2% sold land or other belongings to pay illness-related costs.

Conclusions

The observed high fatality rate is likely explained by the lack or limited access to efficient antibiotics and under-recognition of the disease among clinicians, which led to inappropriate therapy.