bluuebunny/crossref_metadata_2025 huggingface dataset:
Unsupervised neural networks approach for understanding fraudulent financial reporting
Authors: Huang Shin‐Ying , Tsaih Rua‐Huan , Lin Wan‐Ying
Published: March 2012

Purpose

Creditor reliance on accounting‐based numbers as a persistent and traditional standard to assess a firm's financial soundness and viability suggests that the integrity of financial statements is essential to credit decisions. The purpose of this paper is to provide an approach to explore fraudulent financial reporting (FFR) via growing hierarchical self‐organizing map (GHSOM), an unsupervised neural network tool, to help capital providers evaluate the integrity of financial statements, and to facilitate analysis further to reach prudent credit decisions.

Design/methodology/approach

This paper develops a two‐stage approach: a classification stage that well trains the GHSOM to cluster the sample into subgroups with hierarchical relationship, and a pattern‐disclosure stage that uncovers patterns of the common FFR techniques and relevant risk indicators of each subgroup.

Findings

An application is conducted and its results show that the proposed two‐stage approach can help capital providers evaluate the reliability of financial statements and accounting numbers‐based decisions.

Practical implications

Following the SOM theories, it seems that common FFR techniques and relevant risk indicators extracted from the GHSOM clustering result are applicable to all samples clustered in the same leaf node (subgroup). This principle and any pre‐warning signal derived from the identified indicators can be applied to assessing the reliability of financial statements and forming a basis for further analysis in order to reach prudent decisions. The limitation of this paper is the subjective parameter setting of GHSOM.

Originality/value

This is the first application of GHSOM to financial data and demonstrates an alternative way to help capital providers such as lenders to evaluate the integrity of financial statements, a basis for further analysis to reach prudent decisions. The proposed approach could be applied to other scenarios that rely on accounting numbers as a basis for decisions.
Laser sintering of blended Al‐Si powders
Authors: Olatunde Olakanmi Eyitayo , Dalgarno Kenneth W. , Cochrane Robert F.
Published: March 2012

Purpose

The purpose of this paper is to study the effects of particle size distribution, component ratio, particle packing arrangement, and chemical constitution on the laser sintering behaviour of blended hypoeutectic Al‐Si powders.

Design/methodology/approach

A range of bimodal and trimodal powder blends were created through mixing Al‐12Si and pure aluminium powder. The powder blends were then processed using selective laser sintering to investigate the effect of alloy composition, powder particle size and bed density on densification and microstructural evolution.

Findings

For all of the powder blends the sintered density increases with the specific laser energy input until a saturation level is reached. Beyond this saturation level no further increase in sintered density is obtained for an increase in specific laser energy input. However, the peak density achieved for a given blend varied significantly with the chemical constitution of the alloy, peaking at approximately 9 wt% Si. The tap density of the raw powder mixture (assumed to be representative of bed density) was also a significant factor.

Originality/value

This is the first study to consider the usefulness of silicon as an alloying element in aluminium alloys to be processed by selective laser sintering. In addition the paper outlines the key factors in optimising processing parameters and powder properties in order to attain sound sinterability for direct laser sintered parts.
Influence of surface characteristics on fatigue behaviour of laser sintered plastics
Authors: Blattmeier Monika , Witt Gerd , Wortberg Johannes , Eggert Jan , Toepker Jochen
Published: March 2012

Purpose

The purpose of this paper is to provide macromechanical insight into the fatigue behaviour of laser sintered parts and to understand the influence of the laser sintered surface structure on this behaviour.

Design/methodology/approach

A background on the technological maturity of manufacturing processes and the demand for structural and aesthetic properties of laser sintered plastic products is given. As the contribution of surface structure on part quality was the focus, laser sintered specimens with and without surface finishes, as well as injection moulded specimens were used. The latter simply served as a comparison and was not intended to qualify injection moulding. The study comprises the determination of short‐term tensile properties, the load increase method for investigating fracture and deformation behaviours, and fatigue crack propagation analysis.

Findings

According to the test results, the contribution of laser sintered surface structures to relevant mechanical properties can be neglected. Under dynamic loading conditions, laser sintered specimens achieved a longer lifetime but showed less deformation capabilities in contrast to injection moulded specimens. In general, laser sintered specimens presented considerable resistance to crack initiation and propagation.

Research limitations/implications

Because of the long‐term approach of the research, the number of tests conducted per lot was limited. Thus, the effects of different process settings and the reproducibility could not be fully analysed.

Practical implications

The studied fatigue behaviour of laser sintered specimens has implications for the functional testing of parts or components, for the product and process design as well as for the general compatibility of laser sintering as a manufacturing technology of end‐customer products.

Originality/value

The value of this paper lies in the better understanding of deformation and fracture behaviours of laser sintered polymers.
Study of I‐V characteristics of ZnO film on Si substrate with Ag buffer layer by C‐AFM
Authors: Zhang Yidong , He Weiwei
Published: March 2012

Purpose

The purpose of this paper is to demonstrate the I‐V characteristics of ZnO film on Si substrates with Ag buffer layer by conductive atomic force (C‐AFM).

Design/methodology/approach

An Ag buffer layer and Zn film was first deposited on silicon substrate by RF‐sputtering deposition method from high pure Ag and Zn target, respectively. Then, the deposited film was sintered in air at 500°C for 1 h.

Findings

The structures and morphologies of the prepared films were characterized by X‐ray diffraction (XRD), energy dispersive spectrum (EDS), atomic force microscopy (AFM), and C‐AFM. The results show that the prepared ZnO films with Ag buffer layer have a good crystallinity and surface morphology. Interestingly, the I‐V curve of ZnO film exhibited typical characteristics of semi‐conductive oxide under the conductive Ag buffer layer.

Originality/value

The paper demonstrates, by C‐AFM, that the ZnO/Ag‐buffer/Si exhibits excellent crystal structure, morphology and typical I‐V characteristics.
Dual rate taxed valuation: a more rational approach
Authors: Chan Nelson , Harker Norman
Published: March 2012

Purpose

The purpose of this paper is to re‐visit the problems of taxation consequences of sinking fund in the UK and to look at what is believed to be the only rational reason for using the dual rate adjusted for tax method variant.

Design/methodology/approach

The structure of this paper is: valuing a freehold and a leasehold interest by the single rate gross and net of tax approaches to show the logic that works with freehold valuation interest may not work with leasehold valuation; exploring the tax impacts on sinking fund; resolving the taxation issue of sinking fund; demonstrating the solution to the “double sinking fund problem” by the Greaves method and the single rate net of tax approach; and exploring the future of the dual rate theory.

Findings

The paper confirms that the traditional method is not satisfactory, even after the modifications made by the various methods mentioned above. The single rate net of tax approach is proved to meet all expectations and can be regarded as a more rational approach to the dual rate method.

Practical implications

Valuers of the “UK School” might consider that not only should dual rate valuation be regarded as defunct, but also that the more appropriate approach might be to move to a net of taxation approach.

Originality/value

This paper is the original work of the authors.
Risk and uncertainty in development
Authors: Loizou Pavlos , French Nick
Published: March 2012

Purpose

The purpose of this paper is to deal with the appropriateness of using the Monte Carlo simulation as a technique to calculate risk in real estate development.

Design/methodology/approach

The paper is divided into two interlinked segments. The first segment examines the general definition of risk and Monte Carlo simulation methodology as a tool to estimate risk. The second outlines the appropriateness of using Monte Carlo as a tool to model real estate development, given the lack of data quality and its inability to account for human relationships in the development process.

Findings

It is important that the Monte Carlo Simulation model is used as prescriptive model that builds on the original elicitation procedures; produces initial results; allows for detailed sensitivity analysis and then remodels as required. In short, to be fully effective, the Monte Carlo Simulation model needs to be used in a complementary fashion with an understanding of human judgement and decision making.

Research limitations/implications

A fuller analysis may include an examination of the uncertainties in each of the components of the appraisal and account for the appropriate distributions of each of these variables. This is generally referred to as a Monte Carlo simulation. The argument in favour of a Monte Carlo simulation is that it helps the appraiser have a better understanding of the possible outcomes for the development and the relative impact of each input in the pricing of the project.

Practical implications

A lot of work has been done looking at scenario modelling with probabilities and the results that ensue. However, it is important that these quantitative results are placed in the context of the heuristic and cognitive approaches adopted by the decision maker. In other words, the behaviour of the decision maker is as influential in the interpretation of the results as the numbers themselves. This paper looks at the advantages and disadvantages of using Monte Carlo simulation in this context.

Originality/value

This study contributes significantly to the practical application of probability‐based models to development appraisal. The findings of the study are useful for users of feasibility studies to understand the context in which a development feasibility is carried out, and for appraisers to extend the scope of their analysis when carrying them out.
Winning by thinking: how to create a culture of thought leadership in your organization
Authors: Gibbins‐Klein Mindy
Published: March 2012

Purpose

The article was written to highlight the features within thought leadership, described within four subject headings, which can altogether contribute to developing a culture of thought leadership in any organization.

Design/methodology/approach

Set out in four easy steps, this article is designed to take the reader through the process of thought leadership and its development within an organization.

Findings

The article highlights the benefits of encouraging a thought leadership culture within an organization. It enhances the company name and it makes for more credibility and recognition.

Practical implications

Companies cannot be strong without good thought leadership – therefore it is important to bring out your organization's best thought leaders for ultimate recognition.

Originality/value

This paper sets out a framework for individuals and organizations to plan how to gain recognition as “thought leaders” in their industry – a crucial capability as technology makes the world ever smaller.
From “necessary evil” to necessity: stakeholders' involvement in place branding
Authors: Kavaratzis Mihalis
Published: March 2012

Purpose

The purpose of this paper is to focus on the role of stakeholders in the creation, development and ultimately ownership of place brands. The paper contributes towards laying the foundations of a participatory view of place branding. It establishes an urgent need to rethink place branding towards a more participation‐oriented practice. This is based on the centrality of stakeholders in the creation, development and ownership of place brands. The role of stakeholders goes well beyond that of customers/consumers as they are citizens who legitimize place brands and heavily influence their meaning.

Design/methodology/approach

The paper highlights a turn towards stakeholder‐oriented place branding in recent literature. This is contrasted to a critical evaluation of place branding practice where stakeholders are paid “lip service” regarding their participation, rather than being given opportunities to get more fully involved in the development of their place brand.

Findings

An emerging discussion is identified on the significance of stakeholders. This is integrated with additional arguments for stakeholders' participation found in the political nature of place branding, in the concept of “participatory branding” and in the changes that on‐line communication has brought about.

Practical implications

The participatory approach introduced here re‐evaluates the role of both stakeholders and place brand managers. It also implies a significant change in the perceived role of analysis within the place branding process. A re‐direction of branding budgets is also suggested.

Originality/value

The paper provides a clear description of the role of stakeholders in place branding. It brings together for the first time in an integrated manner several arguments for stakeholders' participation. These lead to the conclusion that effective place brands are rooted in the involvement of stakeholders and substantiate the call made here for participatory place branding.
Common or competing products? Towards supra‐national branding in BaltMet Promo
Authors: Andersson Marcus , Paajanen Malla
Published: March 2012

Purpose

Since early 2000s, several efforts have been initiated to market the Baltic Sea Region (BSR) globally, and the BaltMet Promo project is among them. Simultaneously, several other cases of supra‐national branding have emerged, e.g. the Greater Mekong region, Danube region, and Visegrad countries. Little attention has yet been paid in the literature to branding of supra‐national entities. The purpose of this paper is to discuss branding of BSR using the examples of supra‐national product building of the BaltMet Promo project (2010‐2011).

Design/methodology/approach

Branding BSR has faced criticism against its supra‐national perspective which may be seen as a direct competitor to city or nation branding. To shift from competition to cooperation BaltMet Promo acknowledged a bottom‐up approach and nine organisations from six countries created supra‐national products to promote tourism, talent attraction, and investments. Each product concept was built on intensive background research and transnational triple‐helix cooperation.

Findings

The case of BaltMet Promo shows that supra‐national branding benefits from a bottom‐up approach that uses concrete products and services as the core of the brand identity. To shift from competition to cooperation the partnership promoted BSR as a common region with a common work plan. Different scales of branding serve different markets. The more distant the market, such as Japan in the case of BaltMet Promo, the more cost effective supra‐regional branding becomes compared to more narrow scales of branding.

Originality/value

The paper introduces recent developments in supra‐national branding using data of the BaltMet Promo project. The analysis aims to contribute to product building, triple helix stakeholder cooperation, and policy making.
Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients
Authors: Suyagh Maysa , Hawwa Ahmed F. , Collier Paul S. , Millership Jeffrey S. , Kole Prashant , Millar Muriel , Shields Mike D. , Halliday Henry L. , McElnay James C.
Published: February 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients

WHAT THIS STUDY ADDS

• A population pharmacokinetic model has been developed to evaluate the pharmacokinetics of canrenone in paediatric patients who received potassium canrenoate as part of their therapy in the intensive care unit.

AIMS To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate to paediatric patients.

METHODS Data were collected prospectively from 23 paediatric patients (2 days to 10 years of age; median weight 4 kg, range 2.16–28.0 kg) who received intravenous potassium canrenoate (K‐canrenoate) as part of their intensive care therapy for removal of retained fluids, e.g. in pulmonary oedema due to chronic lung disease and for the management of congestive heart failure. Plasma samples were analyzed by HPLC for determination of canrenone (the major metabolite and pharmacologically active moiety) and the data subjected to pharmacokinetic analysis using NONMEM.

RESULTS A one compartment model best described the data. The only significant covariate was weight (WT). The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) were CL/F (l h−1) = 11.4 × (WT/70.0)0.75 and V/F (l) = 374.2 × (WT/70) where WT is in kg. The values of CL/F and V/F in a 4 kg child would be 1.33 l h−1 and 21.4 l, respectively, resulting in an elimination half‐life of 11.2 h.

CONCLUSIONS The range of estimated CL/F in the study population was 0.67–7.38 l h−1. The data suggest that adjustment of K‐canrenoate dosage according to body weight is appropriate in paediatric patients.
Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: a United Kingdom multicentre retrospective experience
Authors: Samarasinghe Sujith , Steward Colin , Hiwarkar Prashant , Saif Muhammad Ameer , Hough Rachael , Webb David , Norton Alice , Lawson Sarah , Qureshi Amrana , Connor Philip , Carey Peter , Skinner Rod , Vora Ajay , Pelidis Maria , Gibson Brenda , Stewart Graham , Keogh Steve , Goulden Nick , Bonney Denise , Stubbs Mathew , Amrolia Persis , Rao Kanchan , Meyer Stefan , Wynn Rob , Veys Paul
Published: February 2012

We retrospectively analysed the outcome of consecutive children with idiopathic severe aplastic anaemia in the United Kingdom who received immunosuppressive therapy (IST) or matched unrelated donor (MUD) haematopoietic stem cell transplantation (HSCT). The 6‐month cumulative response rate following rabbit antithymocyte globulin (ATG)/ciclosporin (IST) was 32·5% (95% CI 19·3–46·6) (n = 43). The 5‐year estimated failure‐free survival (FFS) following IST was 13·3% (95% confidence interval [CI] 4·0–27·8). In contrast, in 44 successive children who received a 10‐antigen (HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1) MUD HSCT there was an excellent estimated 5‐year FFS of 95·01% (95% CI 81·38–98·74). Forty of these children had failed IST previously. HSCT conditioning was a fludarabine, cyclophosphamide and alemtuzumab (FCC) regimen and did not include radiotherapy. There were no cases of graft failure. Median donor chimerism was 100% (range 88–100%). A conditioning regimen, such as FCC that avoids total body irradiation is ideally suited in children. Our data suggest that MUD HSCT following IST failure offers an excellent outcome and furthermore, if a suitable MUD can be found quickly, MUD HSCT may be a reasonable alternative to IST.
Understanding trait interactions and their impacts on growth in Scots pine branches across Europe
Authors: Sterck Frank J. , Martínez‐Vilalta Jordi , Mencuccini Maurizio , Cochard Hervé , Gerrits Pieter , Zweifel Roman , Herrero Asier , Korhonen Janne F.J. , Llorens Pilar , Nikinmaa Eero , Nolè Angelo , Poyatos Rafael , Ripullone Francesco , Sass‐Klaassen Ute
Published: February 2012

1. Plants exhibit a wide variety in traits at different organizational levels. Intraspecific and interspecific studies have potential to demonstrate functional relationships and trade‐offs amongst traits, with potential consequences for growth. However, the distinction between the correlative and functional nature of trait covariation presents a challenge because traits interact in complex ways.

2. We present an intraspecific study on Scots pine branches and use functional multi‐trait concepts to organize and understand trait interactions and their impacts on growth. Branch‐level traits were assessed for 97 branches from 12 Scots pine sites across Europe.

3. To test alternative hypotheses on cause–effect relationships between anatomical traits, hydraulic traits and branch growth, we measured for each branch: the tracheid hydraulic diameter, double cell wall thickness, cell lumen span area, wood density, cavitation vulnerability, wood‐specific hydraulic conductivity, the leaf area to sapwood area ratio and branch growth. We used mixed linear effect models and path models to show how anatomical traits determine hydraulic traits and, in turn, how those traits influence growth.

4. Tracheid hydraulic diameter was the best predictor of cavitation vulnerability (R2 = 0·09 explained by path model) and specific conductivity (R2 = 0·19) amongst anatomical traits. Leaf area to sapwood area ratio had the strongest direct effect on branch growth (R2 = 0·19) and was positively associated with the tracheid hydraulic diameter (R2 = 0·22). A number of bivariate correlations between traits could be explained by these functional relationships amongst traits.

5. The plasticity in tracheid hydraulic diameter (10.0–15.1 μm) and leaf area to sapwood area ratio (600–6051 cm2 cm−2) and the maintenance of a minimum leaf water potential (between −2 and −2·5 MPa) appear to drive the anatomical and hydraulic traits of Scots pine across Europe. These properties are major drivers of the functional trait network underlying the growth variation amongst pine branches and thus possibly contribute to the ecological success of pines at a local and continental scale.
Immigrants and refugees: the importance of dispersal in mediating biotic attrition under climate change
Authors: Anderson Alex S. , Reside April E. , VanDerWal Jeremy J. , Shoo Luke P. , Pearson Richard G. , Williams Stephen E.
Published: March 2012

Montane tropical rainforests are critically important areas for global bird diversity, but are projected to be highly vulnerable to contemporary climate change. Upslope shifts of lowland species may partially offset declines in upland species but also result in a process of lowland biotic attrition. This latter process is contingent on the absence of species adapted to novel warm climates, and isolation from pools of potential colonizers. In the Australian Wet Tropics, species distribution modelling has forecast critical declines in suitable environmental area for upland endemic birds, raising the question of the future role of both natural and assisted dispersal in species survival, but information is lacking for important neighbouring rainforest regions. Here we use expanded geographic coverage of data to model the realized distributions of 120 bird species found in north‐eastern Australian rainforest, including species from potential source locations in the north and recipient locations in the south. We reaffirm previous conclusions as to the high vulnerability of this fauna to global warming, and extend the list of species whose suitable environmental area is projected to decrease. However, we find that expansion of suitable area for some species currently restricted to northern rainforests has the potential to offset biotic attrition in lowland forest of the Australian Wet Tropics. By examining contrasting dispersal scenarios, we show that responses to climate change in this region may critically depend on dispersal limitation, as climate change shifts the suitable environmental envelopes of many species south into currently unsuitable habitats. For lowland and northern species, future change in vegetation connectivity across contemporary habitat barriers is likely to be an important mediator of climate change impacts. In contrast, upland species are projected to become increasingly isolated and restricted. Their survival is likely to be more dependent on the viability of assisted migration, and the emergence and persistence of suitable environments at recipient locations.
Improving in sacco incubation technique to evaluate fresh forage for selecting fast‐degrading perennial ryegrass (Lolium perenne L.)
Authors: Sun X. Z. , Waghorn G. C.
Published: February 2012

Grasses with fast fibre degradation are required by intensive pasture‐based animal production systems to maximize intakes and productivity. To select fast‐degrading elite cultivars, a repeatable, rapid and inexpensive screening method should be developed, so large numbers of samples can be evaluated. This study refined the experimental procedure for the in sacco incubation technique using fresh (not dried) perennial ryegrass (Lolium perenne L.). Pre‐ruminal incubation treatment and ratio of forage weight to the surface area of the in sacco bag have been tested to evaluate their effects on ryegrass degradation kinetic parameters in the bovine rumen. The timing of sampling and the number of sampling time points were also examined. Results indicated that warming the bags in water prior to incubation led to a faster dry‐matter (DM) degradation in the first 12 h. If ratio of forage to bag surface area was between 26 and 45 mg DM cm−2, degradation parameters were not affected by bag fill. Sampling between 9 and 12 h was critical for determining degradation rate. From these results, an improved in sacco incubation procedure is recommended for screening of ryegrasses used for cultivar selection. The principles demonstrated here for ryegrass may be applicable to other forages, although the critical sampling times for measuring degradation rate are likely to differ.
Meta‐analysis of the effectiveness of chronic care management for diabetes: investigating heterogeneity in outcomes
Authors: Elissen Arianne M. J. , Steuten Lotte M. G. , Lemmens Lidwien C. , Drewes Hanneke W. , Lemmens Karin M. M. , Meeuwissen Jolanda A. C. , Baan Caroline A. , Vrijhoef Hubertus J. M.
Published: February 2012

Purpose  The study aims to support decision making on how best to redesign diabetes care by investigating three potential sources of heterogeneity in effectiveness across trials of diabetes care management.

Methods  Medline, CINAHL and PsycInfo were searched for systematic reviews and empirical studies focusing on: (1) diabetes mellitus; (2) adult patients; and (3) interventions consisting of at least two components of the chronic care model (CCM). Systematic reviews were analysed descriptively; empirical studies were meta‐analysed. Pooled effect measures were estimated using a meta‐regression model that incorporated study quality, length of follow‐up and number of intervention components as potential predictors of heterogeneity in effects.

Results  Overall, reviews (n = 15) of diabetes care programmes report modest improvements in glycaemic control. Empirical studies (n = 61) show wide‐ranging results on HbA1c, systolic blood pressure and guideline adherence. Differences between studies in methodological quality cannot explain this heterogeneity in effects. Variety in length of follow‐up can explain (part of) the variability, yet not across all outcomes. Diversity in the number of included intervention components can explain 8–12% of the heterogeneity in effects on HbA1c and systolic blood pressure.

Conclusions  The outcomes of chronic care management for diabetes are generally positive, yet differ considerably across trials. The most promising results are attained in studies with limited follow‐up (<1 year) and by programmes including more than two CCM components. These factors can, however, explain only part of the heterogeneity in effectiveness between studies. Other potential sources of heterogeneity should be investigated to ensure implementation of evidence‐based improvements in diabetes care.
Vertical and horizontal photobiont transmission within populations of a lichen symbiosis
Authors: DAL GRANDE F. , WIDMER I. , WAGNER H.H. , SCHEIDEGGER C.
Published: March 2012

Lichens are widespread symbioses and play important roles in many terrestrial ecosystems. The genetic structure of lichens is the result of the association between fungal and algal populations constituting the lichen thallus. Using eight fungus‐ and seven alga‐specific highly variable microsatellite markers on within‐population spatial genetic data from 62 replicate populations across Europe, North America, Asia and Africa, we investigated the contributions of vertical and horizontal transmission of the photobiont to the genetic structure of the epiphytic lichen Lobaria pulmonaria. Based on pairwise comparisons of multilocus genotypes defined separately for the mycobiont and for the photobiont, we inferred the transmission mode of the photobiont and the relative contribution of somatic mutation and recombination. After constraining the analysis of one symbiont to pairs of individuals with genetically identical symbiotic partners, we found that 77% of fungal and 70% of algal pairs were represented by clones. Thus, the predominant dispersal mode was by means of symbiotic vegetative propagules (vertical transmission), which dispersed fungal and algal clones co‐dependently over a short distance, thus shaping the spatial genetic structure up to distances of 20 m. Evidence for somatic mutation generating genetic diversity was found in both symbionts, accounting for 30% of pairwise comparisons in the alga and 15% in the fungus. While the alga did not show statistically significant evidence of recombination, recombination accounted for 7.7% of fungal pairs with identical algae. This implies that, even in a mostly vegetatively reproducing species, horizontal transmission plays a role in shaping the symbiotic association, as shown in many coral and other symbioses in nature.
Membrane translocation of diphtheria toxin fragment A exploits early to late endosome trafficking machinery
Authors: Lemichez Emmanuel , Bomsel Morgane , Devilliers Ginette , van der Spek Johanna , Murphy John R. , Lukianov Evgenij V. , Olsnes Sjur , Boquet Patrice
Published: February 2012

After reaching early endosomes by receptor‐mediated endocytosis, diphtheria toxin (DT) molecules have two possible fates. A large pool enters the degradative pathway whereas a few molecules become cytotoxic by translocating their catalytic fragment A (DTA) into the cytosol. Impairment of DT degradation by microtubule depolymerization does not block DT cytotoxicity. Therefore, DTA membrane translocation into the cytosol occurs from an endocytic compartment located upstream of late endosomes. Comparisons between early endosomes and endocytic carrier vesicles in a cell‐free translocation assay have demonstrated that early endosomes are the earliest endocytic compartment from which DTA translocates. DTA translocation is ATP‐dependent, requires early endosomal acidification, and is increased by the addition of cytosol. Cytosol‐dependent DTA translocation is GTPγS‐insensitive but is blocked by anti‐βCOP antibodies.
Identification and analysis of flagellar coexpressed determinants (Feds) of Campylobacter jejuni involved in colonization
Authors: Barrero‐Tobon Angelica M. , Hendrixson David R.
Published: February 2012

The flagellum of Campylobacter jejuni provides motility essential for commensal colonization of the intestinal tract of avian species and infection of humans resulting in diarrhoeal disease. Additionally, the flagellar type III secretion system has been reported to secrete proteins such as CiaI that influence invasion of human intestinal cells and possibly pathogenesis. The flagellar regulatory system ultimately influences σ28 activity required for expression of the FlaA major flagellin and other flagellar filament proteins. In this work, we discovered that transcription of ciaI and four genes we propose annotating as feds (for flagellar coexpressed determinants) is dependent upon σ28, but these genes are not required for motility. Instead, the Feds and CiaI are involved in commensal colonization of chicks, with FedA additionally involved in promoting invasion of human intestinal cells. We also discovered that the major flagellin influences production, stability or secretion of σ28‐dependent proteins. Specific transcriptional and translational mechanisms affecting CiaI were identified and domains of CiaI were analysed for importance in commensalism or invasion. Our work broadens the genes controlled by the flagellar regulatory system and implicates this system in co‐ordinating production of colonization and virulence determinants with flagella, which together are required for optimal interactions with diverse hosts.
Next‐generation sequencing: ready for the clinics?
Authors: Desai AN , Jere A
Published: February 2012

Desai AN, Jere A. Next‐generation sequencing: ready for the clinics?

Next‐generation sequencing (NGS) has transformed genomic research by decreasing the cost of sequencing and increasing the throughput. Now, the focus is on using NGS technology for diagnostics and therapeutics. In this review, we discuss the possible clinical applications of NGS and the potential of some of the current systems to transition to the clinic. Clinical use of NGS technologies will enable the identification of causative mutations for rare genetic disorders through whole‐genome or targeted genome resequencing, rapid pathogen screening and cancer diagnosis along with the identification of appropriate therapy. Routine clinical use of NGS technologies is appealing, but mandates high accuracy, simple assays, small inexpensive instruments, flexible throughput, short run times and most importantly, easy data analysis as well as interpretation. A number of NGS systems launched recently have least some of these characteristics, namely, small instruments, flexible throughput and short run time, but still face a few challenges. Moreover, simplified data analysis tools will need to be developed to minimize the requirement of sophisticated bioinformatics support in clinics. In summary, for successful transition of NGS to clinic, a sustained collaboration between research labs, clinical practitioners and vendors offering sequencing based genetic tests is required.
The Breed and Season Effects on Scrotal Circumference and Semen Characteristics of Hair Sheep Rams Under Tropical Conditions
Authors: Cárdenas‐Gallegos MA , Aké‐López JR , Centurión‐Castro F , Magaña‐Monforte JG
Published: February 2012

Contents

The aim of the present work was to evaluate the breed and season effects on scrotal circumference (SC) and semen characteristics of 28 mature hair sheep rams kept under tropical conditions. SCs, sperm concentration (SPC) and abnormal sperm were significantly affected by breed effect (p < 0.001). The season effect was significant in SPC (p < 0.0001) while ejaculate volume, mass motility and SPC were affected by breed × season interaction effect (p < 0.001). It can be concluded that the magnitude of the breed and season effects were not sufficient to affect the reproductive capacity of hair sheep rams throughout the year.
Birth by cesarean section is associated with elevated neonatal plasma levels of dimethylarginines
Authors: Vida Gabriella , Sulyok Endre , Ertl Tibor , Martens‐Lobenhoffer Jens , Bode‐Böger Stefanie M.
Published: February 2012

Background:  This study was undertaken to compare the effects of vaginal delivery and cesarean section on the l‐arginine‐nitric oxide system by measuring levels of l‐arginine, an endogenous nitric oxide synthase antagonist asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in the cord blood and postnatally.

Methods:  Plasma samples were obtained from the umbilical vein and artery at birth and from peripheral venous blood on the second postnatal day in 30 full‐term newborn infants: 10 born vaginally and 20 born by cesarean section.

Results:  After vaginal delivery, ADMA concentration was higher in the umbilical vein than in the umbilical artery (mean 1.06 vs 0.90 µmol/L [P= 0.027]); and ADMA level fell after birth to 0.66 µmol/L on the second postnatal day (P= 0.007 vs umbilical artery). Newborns born by cesarean section had similar ADMA levels in umbilical arterial and venous blood, 1.19 and 1.18 µmol/L, and the ADMA level fell to 0.84 µmol/L by the second postnatal day (P < 0.001). Vaginal birth induced neither significant umbilical venoarterial difference nor a postnatal fall in SDMA. After cesarean section, SDMA was essentially the same in umbilical vein, umbilical artery and postnatal peripheral vein samples. At 2 days of age, both ADMA and SDMA levels stayed higher in infants born by cesarean section than in vaginally born infants.

Conclusions:  ADMA level falls after both vaginal and cesarean birth, whereas SDMA level does not. The higher ADMA level after cesarean birth compared with vaginal birth may contribute to decreased nitric oxide production and bioavailability in neonatal vascular beds.
Involvement of estrogen receptors in prostatic diseases
Authors: Kawashima Hidenori , Nakatani Tatsuya
Published: February 2012

Accumulating evidence shows that estrogens participate in the pathogenesis and development of benign prostatic hyperplasia and prostate cancer by activating estrogen receptor α. In contrast, estrogen receptor β is involved in the differentiation and maturation of prostatic epithelial cells, and thus possesses antitumor effects in prostate cancer. However, the natural ligands of estrogen receptor β are not fully understood, and its mode of action according to its ligands and the binding sites located in the promoter regions of downstream genes remains to be elucidated. Here, we review recent experimental investigations of estrogen receptors and their urological relevance. Estrogen receptor‐mediated signaling in the prostate is essential together with the androgen receptor‐mediated pathway, providing a new therapeutic target for prostatic diseases.
Promoting Multifoci Citizenship Behavior: Time‐Lagged Effects of Procedural Justice, Trust, and Commitment
Authors: Lehmann‐Willenbrock Nale , Grohmann Anna , Kauffeld Simone
Published: February 2012

To explain why procedural justice leads to organisational citizenship behavior (OCB), both commitment and trust have been studied—but never concurrently. Moreover, as employees aim their behaviors toward distinct targets in the workplace, citizenship behaviors as well as commitment and trust should be considered as multifoci constructs. To address this, 204 industrial workers were surveyed over a period of three years. Data were analysed with Mplus using structural equation modeling. Our time‐lagged findings show that procedural justice was linked to OCB, and that this link was mediated successively by trust and commitment. Moreover, we found target‐specific effects: Procedural justice effects on organisational citizenship behavior were mediated by organisational trust and organisational commitment, whereas procedural justice effects on co‐worker citizenship behavior were mediated by co‐worker trust and co‐worker commitment. These results underscore the importance of including multifoci trust for understanding the procedural justice–OCB link. We discuss theoretical implications for studying target‐specific citizenship behaviors and their antecedents, and deduce practical implications for fostering multifoci citizenship behaviors.
A randomized non‐inferiority study comparing the addition of exenatide twice daily to sitagliptin or switching from sitagliptin to exenatide twice daily in patients with Type 2 diabetes experiencing inadequate glycaemic control on metformin and sitagliptin
Authors: Violante R. , Oliveira J. H. A. , Yoon K.‐H. , Reed V. A. , Yu M. B. , Bachmann O. P. , Lüdemann J. , Chan J. Y. C.
Published: February 2012

Aims  To test the hypothesis that glycaemic control achieved when switching sitagliptin to exenatide twice daily plus metformin is non‐inferior to adding exenatide twice daily to sitagliptin and metformin.

Methods  Patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin were randomly assigned to 20 weeks of treatment with twice‐daily exenatide plus placebo and metformin (SWITCH, n = 127) or twice‐daily exenatide plus sitagliptin and metformin (ADD, n = 128).

Results  Non‐inferiority (0.4% margin) of SWITCH to ADD treatment, measured by change in HbA1c from baseline to week 20, was not shown {between‐treatment difference in least‐squares mean [95% CI 3 mmol/mol (0.30%)] [0.8–5.8 (0.07–0.53)]}. A greater reduction (P = 0.012) in HbA1c [least‐squares mean (se)] was experienced by patients in the ADD group {−7 mmol/mol [−0.68%] [0.9 (0.08)]}, compared with those in the SWITCH group {−4 mmol/mol [−0.38%] [1.0 (0.09)]} and a greater proportion (P = 0.027) of patients in the ADD group (41.7%) reached < 7.0% (< 53 mmol/mol) HbA1c target, compared with those in the SWITCH group (26.6%) by week 20. Patients in the ADD group experienced greater fasting serum glucose (P = 0.038) and daily mean postprandial self‐monitored blood glucose (P = 0.048) reductions, compared with patients in the SWITCH group, by week 20. Patients in both groups experienced a lower incidence of nausea and vomiting compared with previous exenatide studies.

Conclusions  Non‐inferiority of SWITCH to ADD treatment was not supported by the results of this study. In patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin, adding exenatide provided better glycaemic control than switching to exenatide. These results are consistent with the clinical approach that adding is better than switching to another oral anti‐hyperglycaemic medication.
Making Development Assistance More Effective Through Using Political‐economy Analysis: What Has Been Done and What Have We Learned?
Authors: Duncan Alex , Williams Gareth
Published: March 2012

Politics often explains where development assistance has been effective and where it has not. Yet, until the 2000s there has been little focus by development agencies on political issues. This has recently begun to change with political‐economy analysis (PEA) now being more systematically used by development agencies to understand the real world. Nigeria and Bangladesh are two positive examples. Much remains to be done in these countries and more widely, to ensure stronger uptake of PEA. On the supply side this includes getting the ‘product’ right, and better communicating the message. On the demand side, there is a need to take more account of the incentives facing development agencies and to gather more systematic evidence on the operational impact of PEA to date.
Како сделан Акакий: Letter as Hero in “The Overcoat”
Authors: SCOLLINS KATHLEEN
Published: March 2012

Recent scholars have construed Gogol's “Overcoat,” along with its hero Akakii Akakievich, as pure literary performance. Popkin represents the inarticulate copy‐clerk as “little more than a verbal artifact,” while Bernheimer describes Akakii as “a text … that can be deciphered not as a series of significant signs but only as a succession of discrete letters.” This article pursues a very literal extension of this line of critical investigation, presenting Akakii as an individual alphabetic character in search of context, difference and, ultimately, meaning. The 1820s and 1830s in Russia witnessed a marked revival of concern with the form and significance of the alphabet. During these years, orthographic issues were widely reported in the press and debated in scholarly circles. The old tradition of anthropomorphic alphabets, which had several well‐known precedents in the eighteenth century, underwent a simultaneous renaissance in the years just preceding Gogol's composition of “Overcoat.” Indeed, according to Vaiskopf, the period in question saw a rebirth of a playful tradition allegorically associating the letters of the alphabet with the Russian bureaucratic hierarchy. Gogol would undoubtedly have been familiar with the issues and polemics surrounding the alphabet, and with the proliferation of literary responses to the orthographic question. The text of Gogol's “Overcoat” incorporates numerous hints about Akakii's familiar relationship with letters: he copies them lovingly, winks and laughs at his favorites, and sees them superimposed on the outer world. Earlier drafts of the story include the names of specific old Cyrillic letters, unambiguously suggesting their embodiment in the story's hero. Akakii's obsession with letters extends only as far as their form, however; unable to wield words to create meaning, he is interested solely in their outward shape and reproduction, rather than their content. This paper will explore “Overcoat” as Gogol's unique literary transformation of the alphabet question, in which Akakii represents a solitary, unsignifying signifier.
The St. Petersburg Literacy Committee and Russian Education: Government Tutelage or Public Trust?
Authors: BRADLEY JOSEPH
Published: March 2012

Although the relationship between Russian government and society in the nineteenth century is often portrayed in terms of conflict, cooperation was more typically the rule. The tsarist state encouraged, sanctioned and patronized private associations dedicated to the pursuit of national betterment and the prestige of the realm. The interests of state and society appeared to be shared interests, and on many projects monarchy and officialdom were willing to collaborate with private individuals. However, the increasing civic activism of private associations during the second half of the nineteenth century challenged the authorities' ability to control the public sphere, and the relationship between state and society turned gradually from cooperation to conflict. We may chart the trajectory from cooperation to confrontation by examining the Free Economic Society's involvement in education. Although the government bureaucracy, the zemstvos, and teachers' professional organizations have received the attention of historians, less is known about the work of Russia's science societies. The involvement of private associations in popular education during the second half of the nineteenth century demonstrates the opportunities, as well as the limitations, of nongovernmental public action. An examination of a division of the Free Economic Society known as the Literacy Committee will also provide a case study of the interaction between officialdom, an association, and the broader public as well as an example of the horizontal linkages in society that associations facilitated. The initial partnership between state and society turned into conflict, as the Literacy Committee spearheaded a rise in public activity in the 1890s. This civic activism, as well as the claim of the Literacy Committee's leaders to a voice in public policy, raised the specter of a vast archipelago of unauthorized and unscrutinized public initiative in education; conflict more and more entered into the relationship between government and society. By operating in a legally sanctioned public sphere and by mobilizing a public, the Literacy Committee, along with other education associations, the zemstvos and the city councils, were a lever used by activists in an attempt to wrest education from government tutelage. However constrained by the government, participation in nongovernmental associations gave the public a voice and allowed activists to challenge government tutelage. Using the vehicle of the association, Russian education activists framed public opinion, organized public meetings around issues of concern, and claimed an advocacy role in public policy.