bluuebunny/crossref_metadata_2025 huggingface dataset:
The combined use of disease activity and infliximab serum trough concentrations for early prediction of (non‐)response to infliximab in rheumatoid arthritis
Authors: van den Bemt Bart J. F. , den Broeder Alfons A. , Wolbink Gert‐Jan , van den Maas Aatke , Hekster Yechiel A. , van Riel Piet L. C. M. , Benraad H. Bart , van den Hoogen Frank H. J.
Published: April 2013

Aim

Early prediction of (non‐)response to infliximab therapy can improve therapeutic benefit by avoiding unnecessary periods of high disease activity during ineffective therapy. This prospective cohort study therefore aimed to study the predictive value of (1) disease activity alone and (2) infliximab serum trough concentrations in addition to disease activity 6 weeks after start of treatment for achieving low disease activity after 6 months.

Methods

Disease activity and infliximab serum trough concentrations were assessed in all rheumatoid arthritis (RA) patients at 2, 6 and 26 weeks after initiation of infliximab therapy. Receiver operating characteristic (ROC) curves and Youden indices were used to calculate specificity for prediction of good response after 6 months while aiming for maximum sensitivity.

Results

Fifty‐seven consecutive RA patients starting with infliximab therapy were included. After 6 months, 15 (26%, 95 % CI 15, 38%) patients reached good European League against Rheumatism (EULAR) response. A disease activity score <4.2 at 6 weeks after initiation of therapy was a moderate predictor for reaching EULAR response after 6 months (sensitivity 100%, specificity 49%). Infliximab serum trough concentrations (>2.5 mg l−1) as predictor complimentary to disease activity (<4.2) slightly increased the specificity from 49% to 54% without changing the sensitivity (100%). As 39% of the patients did not fulfill at least one of these criteria at week 6, these patients could already be switched to another therapy after 6 weeks.

Conclusions

The combination of disease activity and infliximab serum trough concentrations could be a fair predictor to identify early (after 6 weeks) patients who have insufficient response after 6 months of therapy.
Population pharmacokinetic–pharmacodynamic analysis for eribulin mesilate‐associated neutropenia
Authors: van Hasselt J. G. Coen , Gupta Anubha , Hussein Ziad , Beijnen Jos H. , Schellens Jan H. M. , Huitema Alwin D. R.
Published: April 2013

Aims

Eribulin mesilate is an inhibitor of microtubule dynamics that is approved for the treatment of late‐stage metastatic breast cancer. Neutropenia is one of the major dose‐limiting adverse effects of eribulin. The objective of this analysis was to develop a population pharmacokinetic–pharmacodynamic model for eribulin‐associated neutropenia.

Methods

A combined data set of 12 phase I, II and III studies for eribulin mesilate was analysed. The population pharmacokinetics of eribulin was described using a previously developed model. The relationship between eribulin pharmacokinetic and neutropenia was described using a semi‐physiological lifespan model for haematological toxicity. Patient characteristics predictive of increased sensitivity to develop neutropenia were evaluated using a simulation framework.

Results

Absolute neutrophil counts were available from 1579 patients. In the final covariate model, the baseline neutrophil count (ANC0) was estimated to be 4.03 × 109 neutrophils l−1 [relative standard error (RSE) 1.2%], with interindividual variability (IIV, 37.3 coefficient of variation % [CV%]). The mean transition time was estimated to be 109 h (RSE 1.8%, IIV 13.9CV%), the feedback constant (γ) was estimated to be 0.216 (RSE 1.4%, IIV 12.2CV%), and the linear drug effect coefficient (SLOPE) was estimated to be 0.0451 μg l−1 (RSE 3.2%, IIV 54CV%). Albumin, aspartate transaminase and receival of granulocyte colony‐stimulating factor (G‐CSF) were identified as significant covariates on SLOPE, and albumin, bilirubin, G‐CSF, alkaline phosphatase and lactate dehydrogenase were identified as significant covariates on mean transition time.

Conclusions

The developed model can be applied to investigate optimal treatment strategies quantitatively across different patient groups with respect to neutropenia. Albumin was identified as the most clinically important covariate predictive of interindividual variability in the neutropenia time course.
Rational bystanders
Authors: Greitemeyer Tobias , Mügge Dirk
Published: April 2013

The bystander effect, the phenomenon that the (real or imagined) presence of others inhibits helping, has often been ascribed to bystanders’ apathy. In the present research, we demonstrate that the occurrence of the bystander effect has rational roots. Three studies reveal that the presence of other bystanders does not inhibit helping when effective helping requires more than one help‐giver. Mediation analyses showed that the bystander effect did not occur when many responses were needed because bystanders did not shift responsibility to others when in the presence of other bystanders. These findings suggest that the rational considerations underlying the bystander effect can mitigate the effects of the presence of other bystanders on helping behaviour when more than one help‐giver is needed.
Proposal of a method to assess and report the extent of residual neurovascular tissue present in radical prostatectomy specimens
Authors: Schatloff Oscar , Kameh Darian , Giedelman Camilo , Samavedi Srinivas , Abdul‐Muhsin Haidar , Coelho Rafael F. , Kang Sung Gu , Palmer Kenneth J. , Patel Vipul R.
Published: April 2013

Objective

To propose a method to assess and report the amount of neurovascular tissue present in radical prostatectomy (RP) specimens.

Patients and Methods

The data of 133 consecutive patients who underwent robot‐assisted RP by a single surgeon (V.R.P.) were prospectively collected.

Degree of nerve sparing (NS) was graded intraoperatively by the surgeon independently at either side as complete, partial or none.

A pathologist who was ‘blinded’ to the surgeon's classification measured the following parameters at the posterolateral aspect of the apex, base and mid prostate at either side of the RP specimen: length, width and area of neural tissue, number of nerves per high‐power field and number of total slides containing neural tissue.

Measurements were correlated to the surgeon's intraoperative perception.

Results

All measurements correlated significantly with surgeon's intent of NS at all locations (P = 0.001).

Among them, the cross‐sectional area had the highest correlation coefficient (–0.550 at apex, –0.604 at mid prostate and –0.606 at the base).

Conclusions

The cross‐sectional area of nerve tissue showed the highest correlation with surgeon's intent of NS at all locations.

Having a standardised method of assessing and reporting residual nerve tissue allows the surgeon to objectively evaluate the quality of nerve preservation and to compare the progress of his NS technique over time.
Midterm oncological outcomes of laparoscopic vs open radical prostatectomy (RP)
Authors: Wirth Gregory J. , Psutka Sarah P. , Chapin Brian F. , Wu Shulin , Wu Chin‐Lee , Dahl Douglas M.
Published: April 2013

Objective

To compare the midterm risks of biochemical recurrence (BCR) and salvage radiation therapy (SRT) after laparoscopic (LRP) and open retropubic radical prostatectomy (RRP). Strong evidence that these techniques are comparable to the ‘gold standard’ of open RRP is lacking, as most comparative studies are limited by short follow‐up or rely on historical controls.

Patients and Methods

We studied 1000 consecutive patients concurrently treated by either LRP or RRP between 2001 and 2005.

LRPs were performed by a single surgeon and RRP by four surgeons.

Primary outcomes were BCR and SRT. Survival analysis included relevant clinical and pathological variables.

Results

Of 844 included patients, 244 underwent LRP and 600 RRP.

Clinical and pathological characteristics were similar in both groups. Most patients had Gleason 6 tumours (68%) and pT2 disease (86%). The median follow‐up was 6.1 years and median time to recurrence 3.4 years.

Overall, BCR occurred in 14% of patients: 13.1% after LRP and 14.7% after RRP.

SRT was performed in 10.7% of patients both after LRP and RRP. In uni‐ and multivariate Cox regression models, surgical technique was not a significant predictor of BCR or SRT.

Conclusion

Our results suggest that in high‐volume centres, LRP provides equivalent oncological control to RRP.
Five years in care: documented lives and time trajectories in child welfare
Authors: Pösö Tarja , Eronen Tuija
Published: April 2013

Child welfare practice is temporally structured and includes a variety of follow‐up activities. Practice‐based follow‐up has not, however, been much explored when studying children's paths in the child welfare system. This paper is based on a study of children (103) who were taken into care in 2006 in 10 Finnish municipalities and their paths in care until 2011. The social workers' institutional knowledge of their ‘own’ clients comprises the core of the research design. The paper reflects on the nature of this data from the point of view of the notions of temporality.

The analysis highlights four temporal trajectories used in retrospective analysis of children's paths in care: the linear time trajectory of the decisions and changes in the institutional positions, the temporally fragmentary trajectory of childhood and youth, the circular time trajectory of professional understanding of the child's path and the silent time trajectory. Each one documents the children's paths differently; the linear one tends to be the ‘natural’ and most easily available trajectory and consequently, the children's paths are documented via decisions and institutional positions. The analysis suggests that more attention should be given to the complexity of time and temporality when studying children's paths in child welfare.
Nitroglycerin‐induced changes in facial skin temperature: ‘cold nose’ as a predictor of headache?
Authors: Zaproudina Nina , Närhi Matti , Lipponen Jukka A. , Tarvainen Mika P. , Karjalainen Pasi A. , Karhu Jari , Airaksinen Olavi , Giniatullin Rashid
Published: April 2013

Nitroglycerin (NTG) often induces headaches when used to treat cardiac diseases. Such property of NTG has been widely used in modelling of migraine‐like headaches. However, background reasons, predisposing to the development of NTG‐headache, are less studied. The main aim of our study was to find, using NTG model, easily accessible markers of the vascular changes associated with headache. Because changes in the blood flow alter the local skin temperature (Tsk), we studied the relationship between the regional changes in the facial Tsk and NTG‐induced headaches. Tsk was measured with infrared thermography in 11 healthy women during 3 h after sublingual NTG administration. NTG caused headache in five women, and four of them were the first‐degree relatives of migraine patients. Notably, before NTG administration, subjects in the headache group had lower Tsk values, especially in the nose area, than women in the pain‐free group (n = 6). NTG‐induced headache was associated with a long‐lasting increase of Tsk over the baseline. In sharp contrast, in the pain‐free group, the Tsk reduced and returned rapidly to the baseline. Thus, the low baseline level and greater increase of regional Tsk correlated with the incidence of headache that supports a role of greater vascular changes in headache happening on the basis of the dissimilarities in vascular tone. An easily accessible phenomenon of ‘cold nose’ may indicate background vascular dysfunctions in individuals with predisposition to headache. Facial infrared thermography, coupled with NTG administration, suggests a novel temporally controlled approach for non‐invasive investigation of vascular processes accompanying headaches.
Assessing Research Interest and Capacity in Community Health Centers
Authors: Hacker Karen , Bhuiya Nazmim , Pernice Joan , Khan Sami M. , Sequist Thomas D. , Tendulkar Shalini A.
Published: April 2013

Objective

Community health centers (CHCs) have great potential to participate in the development of evidence‐based primary care but face obstacles to engagement in clinical translational research.

Methods

To understand factors associated with CHC interest in building research infrastructure, Harvard Catalyst and the Massachusetts League of Community Health Centers conducted an online survey of medical directors in all 50 Massachusetts CHC networks.

Results

Thirty‐two (64%) medical directors completed the survey representing 126 clinical sites. Over 80% reported that their primary care providers (PCPs) were slightly to very interested in future clinical research and that they were interested in building research infrastructure at their CHC. Frequently cited barriers to participation in research included financial issues, lack of research skills, and lack of research infrastructure. In bivariate analyses, PCP interest in future clinical research and a belief that involvement in research contributed to PCP retention were significantly associated with interest in building research infrastructure.

Conclusion

CHCs critical role in caring for vulnerable populations ideally positions them to raise relevant research questions and translate evidence into practice. Our findings suggest a high interest in engagement in research among CHC leadership. CTSAs have a unique opportunity to support local CHCs in this endeavor.
Strategies for Mentor Matching: Lessons Learned
Authors: Hacker Beth M. , Subramanian Lalitha , Schnapp Lynn M.
Published: April 2013

Mentoring serves to guide early stage researchers toward opportunities which can further their careers. The most beneficial mentoring experience occurs when both the mentor and mentee share a common background and have appropriate expectations. Our CTSA serves individuals in a five state region with widely disparate needs and we have often struggled to provide appropriate guidance for those requesting mentoring services. Here we present an overview of our past mentor identification strategy along with a proposed new direction to increase flexibility, sustainability and better serve researchers in our region.
Evaluating Various Areas of Process Improvement in an Effort to Improve Clinical Research: Discussions from the 2012 Clinical Translational Science Award (CTSA) Clinical Research Management Workshop
Authors: Strasser Jane E. , Cola Philip A. , Rosenblum Daniel
Published: April 2013

Emphasis has been placed on assessing the efficiency of clinical and translational research as part of the National Institutes of Health (NIH) goal to “improve human health.” Improvements identified and implemented by individual organizations cannot address the research infrastructure needs of all clinical and translational research conducted. NIH's National Center for Advancing Translational Sciences (NCATS) has brought together 61 Clinical and Translational Science Award (CTSA) sites creating a virtual national laboratory that reflects the diversity and breadth of academic medical centers to collectively improve clinical and translational science. The annual Clinical Research Management workshop is organized by the CTSA consortium with participation from CTSA awardees, NIH, and others with an interest in clinical research management. The primary objective of the workshop is to disseminate information that improves clinical research management although the specific objectives of each workshop evolve within the consortium. The fifth annual workshop entitled “Learning by doing; applying evidence‐based tools to re‐engineer clinical research management” took place in June 2012. The primary objective of the 2012 workshop was to utilize data to evaluate, modify, and improve clinical research management. This report provides a brief summary of the workshop proceedings and the major themes discussed among the participants.
Cross‐Sectional Evidence for a Stress‐Negative Affect Pathway to Substance Use among Sexual Minority Girls
Authors: Marshal Michael P. , Burton Chad M. , Chisolm Deena J. , Sucato Gina S. , Friedman Mark S.
Published: April 2013

Sexual minority girls (SMGs) are four times more likely to engage in substance use than are heterosexual girls. A better understanding of the explanatory mechanisms of this disparity is needed to inform prevention and intervention programs. The goal of this study was to conduct a preliminary test of a “stress‐negative affect” pathway by examining gay‐related victimization and depression as mediators of substance use among SMGs. Adolescent girls (N = 156, 41% SMGs) were recruited from two urban adolescent medicine clinics to participate in an NIH‐funded study of adolescent substance use. The average age was 17.0 years old and 57% were nonwhite. Mediation analyses were conducted in a multiple regression framework using SPSS and a mediation macro utilizing bias‐corrected bootstrapping. Four models were estimated to test mediated pathways from sexual orientation to gay‐related victimization (Mediator 1), to depression symptoms (Mediator 2), and then to each of four substance use variables: cigarettes, marijuana, alcohol, and heavy alcohol use. Significant mediated pathways (mediation tests with 95% CIs) were found for cigarette, alcohol and heavy alcohol use outcome variables. Results provide preliminary support for the minority stress hypothesis and the stress‐negative affect pathway, and may inform the development of future prevention and intervention programs.
Pathways of Translation: Deep Brain Stimulation
Authors: Gionfriddo Michael R. , Greenberg Alexandra J. , Wahegaonkar Abhijeet L. , Lee Kendall H.
Published: April 2013

Electrical stimulation of the brain has a 2000 year history. Deep brain stimulation (DBS), one form of neurostimulation, is a functional neurosurgical approach in which a high‐frequency electrical current stimulates targeted brain structures for therapeutic benefit. It is an effective treatment for certain neuropathologic movement disorders and an emerging therapy for psychiatric conditions and epilepsy. Its translational journey did not follow the typical bench‐to‐bedside path, but rather reversed the process. The shift from ancient and medieval folkloric remedy to accepted medical practice began with independent discoveries about electricity during the 19th century and was fostered by technological advances of the 20th. In this paper, we review that journey and discuss how the quest to expand its applications and improve outcomes is taking DBS from the bedside back to the bench.
The Secure Medical Research Workspace: An IT Infrastructure to Enable Secure Research on Clinical Data
Authors: Shoffner Michael , Owen Phillips , Mostafa Javed , Lamm Brent , Wang Xiaoshu , Schmitt Charles P. , Ahalt Stanley C.
Published: April 2013

Clinical data have tremendous value for translational research, but only if security and privacy concerns can be addressed satisfactorily. A collaboration of clinical and informatics teams, including RENCI, NC TraCS, UNC's School of Information and Library Science, Information Technology Service's Research Computing and other partners at the University of North Carolina at Chapel Hill have developed a system called the Secure Medical Research Workspace (SMRW) that enables researchers to use clinical data securely for research. SMRW significantly minimizes the risk presented when using identified clinical data, thereby protecting patients, researchers, and institutions associated with the data. The SMRW is built on a novel combination of virtualization and data leakage protection and can be combined with other protection methodologies and scaled to production levels.
Two‐Dimensional Speckle Tracking Echocardiography for Early Detection of Myocardial Damage in Young Patients with Fabry Disease
Authors: Saccheri María C. , Cianciulli Tomás F. , Lax Jorge A. , Gagliardi Juan A. , Cáceres Guillermo L. , Quarin Alejandra E. , Kisinovsky Isaac , Rozenfeld Paula A. , Reisin Ricardo C. ,   AADELFA
Published: April 2013

Fabry disease (FD) is characterized by left ventricular hypertrophy (LVH). Conventional echocardiography is not sensitive enough to perform the preclinical diagnosis To assess whether longitudinal myocardial strain of the left ventricle (LV), using speckle tracking, is useful to detect early myocardial involvement in FD. Forty‐four patients with FD who were diagnosed with genetic testing were prospectively included and were compared to a sex‐matched control group. They were divided into three groups: 22 with LVH (Group I), 22 without LVH (Group II), and 22 healthy volunteers (Group III). LV longitudinal strain was measured from the apical views. An ANOVA test was used for multiple comparisons for variables with a normal distribution, and a Kruskal–Wallis test was used for variables with non‐Gaussian distribution. Longitudinal LV strain was different in the three groups: it was ≥−15% in at least one segment in all Group I patients, in 50% of patients of Group II and in no patient of Group III. Seventy percent of the segments with abnormal strain in Group II were located in the basal regions (32/46). These findings show that the presence of at least one strain value ≥−15% demonstrates subclinical myocardial dysfunction in patients with preclinical FD. Longitudinal myocardial LV strain measured with speckle tracking is a useful tool to detect early myocardial involvement in young patients with FD. This information allows the detection and treatment of myocardial dysfunction at an early stage, which is of high clinical importance.
Climate change and passive transport of European eel larvae
Authors: Pacariz Selma , Westerberg Håkan , Björk Göran
Published: April 2013

One hypothesis to explain the large decline in the recruitment of the European eel (Anguilla anguilla) from the 1980s onwards is that a change in ocean circulation has influenced the drift of eel larvae, resulting in lower recruitment. To test this hypothesis, a simple Lagrangian model was constructed to simulate a passive drift from the spawning area in the Sargasso Sea to the European shelf. The simulation utilised the velocity data from a reanalysis of ocean climate, the Simple Ocean Data Assimilation (SODA 2.1.6), for the period 1958–2008 covering the time of regime shift in eel recruitment. The average drift time and latitudinal distribution of the arrival of eel larvae were explored for a range of constant depth levels and instantaneous mortalities. The model showed that the proportion of eel larvae carried by the North‐East Atlantic Current to northern latitudes of arrival was greater before 1970, whereas there was an increase in amount of larvae being entrained into the southbound current branches after this time. The overall success of drift from the spawning area to the East Atlantic was not affected and clearly contradicts that this could explain the observed recruitment decline.
Applying the Cognitive Vulnerability Model to the analysis of cognitive and family influences on children's dental fear
Authors: Crego Antonio , Carrillo‐Diaz Maria , Armfield Jason M. , Romero Martin
Published: April 2013

Negative experiences, cognitions, and family variables are involved in the etiology of child dental fear, but previous research has frequently considered them separately. This study uses the Cognitive Vulnerability Model to explore the influence of negative dental experiences and family members on children's dental anxiety. The participants were 185 children who completed a questionnaire comprising measures of dental fear and cognitive vulnerability‐related perceptions. Measures were obtained for 88 of the participants' fathers and for 97 of the participants' mothers. Cognitive vulnerability perceptions had the strongest association with children's dental fear (β = 0.40), explaining 14–21% of the variance in dental fear scores beyond that explained by other variables. Furthermore, vulnerability perceptions mediated the relationship between negative dental experiences and dental fear. Children's dental fear and cognitive vulnerability perceptions were significantly associated with those of their fathers (r = 0.23 and r = 0.40, respectively) and mothers (r = 0.28 and r = 0.35, respectively). Moreover, fathers' (β = 0.24) and mothers' (β = 0.31) levels of cognitive vulnerability significantly predicted the children's levels of dental fear. The Cognitive Vulnerability Model offers a framework to understand child dental fear. Furthermore, this cognitive approach may help explain why some children develop dental fear problems after suffering a negative dental experience and how dental anxiety is passed on from parents to children.
Characteristics of Streptococcus mutans genotypes and dental caries in children
Authors: Cheon Kyounga , Moser Stephen A. , Wiener Howard W. , Whiddon Jennifer , Momeni Stephanie S. , Ruby John D. , Cutter Gary R. , Childers Noel K.
Published: April 2013

This longitudinal cohort study evaluated the diversity, commonality, and stability of Streptococcus mutans genotypes associated with dental caries history. Sixty‐seven 5‐ and 6‐yr‐old children, considered as being at high caries risk, had plaque collected from baseline through 36 months for S. mutans isolation and genotyping using repetitive extragenic palindromic‐PCR (4,392 total isolates). Decayed, missing, or filled surfaces (dmfs (primary teeth)/DMFS (secondary teeth)) for each child were recorded at baseline. At baseline, 18 distinct genotypes were found among 911 S. mutans isolates from 67 children (diversity), and 13 genotypes were shared by at least two children (commonality). The number of genotypes per individual was positively associated with the proportion of decayed surfaces (p‐ds) at baseline. Twenty‐four of the 39 children who were available at follow‐up visits maintained a predominant genotype for the follow‐up periods (stability) and this was negatively associated with the p‐ds. The observed diversity, commonality, and stability of S. mutans genotypes represent a pattern of dental caries epidemiology in this high‐caries‐risk community, which suggests that fewer decayed surfaces are significantly associated with lower diversity and higher stability of S. mutans genotypes.
Oxytocin modulates proliferation and stress responses of human skin cells: implications for atopic dermatitis
Authors: Deing Verena , Roggenkamp Dennis , Kühnl Jochen , Gruschka Alisa , Stäb Franz , Wenck Horst , Bürkle Alexander , Neufang Gitta
Published: April 2013

The neuropeptide hormone oxytocin (OXT) mediates a wide spectrum of tissue‐specific actions, ranging from cell growth, cell differentiation, sodium excretion to stress responses, reproduction and complex social behaviour. Recently, OXT expression was detected in keratinocytes, but expression of its receptor and function are still unexplored in human skin. Here, we showed that both OXT and its receptor are expressed in primary human dermal fibroblasts and keratinocytes. OXT‐induced dose‐dependent calcium fluxes in both cell types demonstrating that the OXT receptor (OXTR) is functionally expressed. We also showed that OXT decreases proliferation of dermal fibroblasts and keratinocytes in a dose‐dependent manner. In order to further investigate OXT‐mediated functions in skin cells, we performed OXTR knockdown experiments. OXTR knockdown in dermal fibroblasts and keratinocytes led to elevated levels of reactive oxygen species and reduced levels of glutathione (GSH). Moreover, OXTR‐depleted keratinocytes exhibited an increased release of the pro‐inflammatory cytokines IL6, CCL5 and CXCL10. Our data indicate that the OXT system modulates key processes which are dysregulated in atopic dermatitis (AD) such as proliferation, inflammation and oxidative stress responses. Furthermore, we detected a downregulation of the OXT system in peri‐lesional and lesional atopic skin. Taken together, these data suggest that the OXT system is a novel neuroendocrine mediator in human skin homoeostasis and clinically relevant to stressed skin conditions like AD.
Learning by Failing: A Simple VaR Buffer
Authors: Boucher Christophe M. , Maillet Bertrand B.
Published: April 2013

We study in this article the problem of model risk in VaR computations and document a procedure for correcting the bias due to specification and estimation errors. This practical method consists of “learning from model mistakes”, since it dynamically relies on an adjustment of the VaR estimates – based on a back‐testing framework – such as the frequency of past VaR exceptions always matches the expected probability. We finally show that integrating the model risk into the VaR computations implies a substantial minimum correction to the order of 10–40% of VaR levels.
CoCo Bonds, Conversion Prices and Risk Shifting Incentives. How Does the Conversion Ratio Affect Management's Behaviour?
Authors: Roggi Oliviero , Giannozzi Alessandro , Mibelli Luca
Published: April 2013

The aim of this paper is to analyze risk shifting incentives for managers and shareholders of the financial institution issuing a CoCo bond. We assess the role of the conversion price settlement in enhancing both shareholders’ and management's discipline. Three recent contingent reverse convertible deals are analyzed, with the intention of showing how shareholder conversion returns are linked to the conversion ratio. The findings demonstrate that, in the case of an ingoing or ongoing crisis, a poor settlement of the conversion ratio could exacerbate both debt overhang and risk shifting issues. This will end in discouraging bank management from issuing new equity and from investing in low risk assets. We argue that a contingent bond triggered on Basel III capital requirement ratios and having a significantly discounted conversion price reduces risk shifting incentives. Moreover, we illustrate how the unexpected wealth transfers between CoCo bondholders and shareholders tends to zero when the bond face value is higher than the current stock market price and there is a concentration of bond subscribers. Accordingly, regulators should consider and oversee not only the conversion trigger but also all the other features of a contingent capital security, especially the conversion ratio.
Ecological response differentials: an alternative benchmark to inform stream and river bioassessment
Authors: Collier Kevin J. , Hamer Mark P.
Published: April 2013

Contemporary patterns of land development mean that suitable reference sites for low‐gradient stream and non‐wadeable river biomonitoring are difficult to locate, requiring alternative approaches for benchmarking human impacts. We use two strongly harmonised macroinvertebrate data sets for wadeable streams (180 sites) and non‐wadeable rivers (30 sites) to (i) quantify metric response differentials across a regional landcover pressure gradient in northern New Zealand; (ii) interpolate reference condition for waterway types lacking comparable reference sites and (iii) inform development of narrative condition bands for data‐poor waterway types.

Cumulative distribution functions of per cent waterway length indicated that near‐shore littoral samples from non‐wadeable rivers had fewer total and EPT (Ephemeroptera, Plecoptera and Trichoptera) taxa than wadeable streams, which had higher % EPT abundance and lower % Crustacea abundance. Community composition differed significantly among non‐wadeable river and wadeable hard‐bottom and soft‐bottom stream samples, reflecting factors associated with catchment altitude, slope, rainfall and landuse intensity.

Ephemeroptera, Plecoptera and Trichoptera richness was the only metric evaluated that significantly reflected landcover across all waterway types. The intercept of the 60th percentile quantile regression line at 100% native vegetation cover provided the best approximation of median EPT taxa richness in an independent reference site data set for hard‐bottom streams. Applying the same interpolation to samples from soft‐bottom streams and non‐wadable rivers that lacked regional reference sites indicated median reference expectations of 9 and 11 EPT taxa, respectively, and a consistent differential across the pressure gradient relative to hard‐bottom streams of seven taxa and five taxa, respectively.

The derived response differentials enabled the development of narrative bands for directly comparing ecological condition of data‐poor stream and river types. Quantification of ecological response differentials can provide an alternative means of benchmarking macroinvertebrate metrics in the absence of suitable reference sites.
Finding the appropriate variables to model the distribution of vector‐borne parasites with different environmental preferences: climate is not enough
Authors: Pérez‐Rodríguez Antón , Fernández‐González Sofía , de la Hera Iván , Pérez‐Tris Javier
Published: April 2013

Understanding how environmental variation influences the distribution of parasite diversity is critical if we are to anticipate disease emergence risks associated with global change. However, choosing the relevant variables for modelling current and future parasite distributions may be difficult: candidate predictors are many, and they seldom are statistically independent. This problem often leads to simplistic models of current and projected future parasite distributions, with climatic variables prioritized over potentially important landscape features or host population attributes. We studied avian blood parasites of the generaPlasmodium,HaemoproteusandLeucocytozoon(which are viewed as potential emergent pathogens) in 37 Iberian blackcapSylvia atricapillapopulations. We used Partial Least Squares regression to assess the relative importance of a wide array of putative determinants of variation in the diversity of these parasites, including climate, landscape features and host population migration. Both prevalence and richness of parasites were predominantly related to climate (an effect which was primarily, but not exclusively driven by variation in temperature), but landscape features and host migration also explained variation in parasite diversity. Remarkably, different models emerged for each parasite genus, although all parasites were studied in the same host species. Our results show that parasite distribution models, which are usually based on climatic variables alone, improve by including other types of predictors. Moreover, closely related parasites may show different relationships to the same environmental influences (both in magnitude and direction). Thus, a model used to develop one parasite distribution can probably not be applied identically even to the most similar host–parasite systems.
Exploring the limits of peak oil: naturalising the political, de‐politicising energy
Authors: Bettini Giovanni , Karaliotas Lazaros
Published: April 2013

Peak oil has acquired prominence in the political lexicon of an increasing number of critical and radical perspectives during the ongoing ecological and economic crisis. By examining examples within academia as well as initiatives such as the Degrowth Movement and the Transition Network, this paper documents how a series of red‐green discourses and movements mobilise the narrative of peak oil as an alarm bell that signals the inevitability of the present ecological crises and of the coming collapse of the fossil‐fuel economy. The paper, developing an analysis on two levels, argues that the ‘red‐green’ mobilisation of peak oil is problematic. First, a close reading of red‐green discourses shows how the weaknesses of the narrative highlighted in the literature (such as a naturalising and de‐politicising understanding of the materiality and finitude of oil) are reproduced by the red‐greens. Second, building on discourse and political theory, the paper highlights that red‐green interpellations of peak oil fail to transcend hegemonic discursive structurations in the field of environmental and energy security, where geopolitical apocalyptic imaginaries and biopolitical forms of securitisation are linked in reproducing post‐politicisation processes. Hence, the paper insists that the invocation of peak oil forecloses the possibilities for radical alternatives to the present socio‐ecological regime of accumulation and circulation.
CaMKIIβ‐mediated LIM‐kinase activation plays a crucial role in BDNF‐induced neuritogenesis
Authors: Saito Akihiko , Miyajima Ken , Akatsuka Junichi , Kondo Hiroshi , Mashiko Toshiya , Kiuchi Tai , Ohashi Kazumasa , Mizuno Kensaku
Published: April 2013

LIM‐kinase 1 (LIMK1) regulates actin cytoskeletal reorganization by phosphorylating and inactivating actin‐depolymerizing factor and cofilin. We examined the role of LIMK1 in brain‐derived neurotrophic factor (BDNF)‐induced neuritogenesis in primary‐cultured rat cortical neurons. Knockdown of LIMK1 or expression of a kinase‐dead LIMK1 mutant suppressed BDNF‐induced enhancement of primary neurite formation. By contrast, expression of an active form of LIMK1 promoted primary neuritogenesis in the absence of BDNF. BDNF‐induced neuritogenesis was inhibited by KN‐93, an inhibitor of Ca2+/calmodulin‐dependent protein kinases (CaMKs), but not by STO‐609, an inhibitor of CaMK‐kinase (CaMKK). CaMKK activity is required for the activation of CaMKI and CaMKIV, but not CaMKII, which suggests that CaMKII is principally involved in BDNF‐induced enhancement of neuritogenesis. Knockdown of CaMKIIβ, but not CaMKIIα, suppressed BDNF‐induced neuritogenesis. Active CaMKIIβ promoted neuritogenesis, and this promotion was inhibited by knockdown of LIMK1, indicating that CaMKIIβ is involved in BDNF‐induced neuritogenesis via activation of LIMK1. Furthermore, in vitro kinase assays revealed that CaMKIIβ phosphorylates LIMK1 at Thr‐508 in the kinase domain and activates the cofilin‐phosphorylating activity of LIMK1. In summary, these results suggest that CaMKIIβ‐mediated activation of LIMK1 plays a crucial role in BDNF‐induced enhancement of primary neurite formation.
In vitro comparison of induction capacity and biomineralization ability of mineral trioxide aggregate and a bioceramic root canal sealer
Authors: Güven E. P. , Taşlı P. N. , Yalvac M. E. , Sofiev N. , Kayahan M. B. , Sahin F.
Published: April 2013

Aim

To compare the effect of mineral trioxide aggregate (MTA) and iRoot SP, a bioceramic root canal sealer, on the cell viability, hard tissue deposition capacity and odontogenic differentiation of human tooth germ stem cells (hTGSCs).

Methodology

The dental materials MTA, iRoot SP and Dycal were packed into Teflon rings and placed on transwell inserts for toxicity evaluations by the MTS assay on days 3 and 7. Dycal was used as a positive control for the cell viability assay. Teflon rings were cocultured with hTGSCs, followed by the induction of odontogenic differentiation. The odontogenic differentiation of hTGSCs and biomineralization ability of the materials were evaluated by analysing the mRNA expression levels of dentine sialophosphoprotein (DSPP) and collagen type 1A (COL1A) by real‐time polymerase chain reaction expression analysis, measurement of alkaline phosphatase (ALP) activity and visualization of calcium deposits by von Kossa staining.

Results

MTA and iRoot SP exhibited no cytotoxicity, but Dycal caused cytotoxicity (P < 0.05) of almost all of the cells after 7 days. MTA significantly stimulated (P < 0.05) the odontogenic differentiation of hTGSCs compared with iRoot SP. MTA and iRoot SP increased (P < 0.05) the mRNA levels of COL1A and DSPP mRNA compared with noninduced hTGSCs, which served as a negative control (NC). iRoot SP, however, significantly decreased (P < 0.05) COL1A and DSPP mRNA expression levels compared with the PC.

Conclusion

MTA and iRoot SP induced hTGSC differentiation into odontoblast‐like cells, but MTA might provide more inductive potential and hard tissue deposition compared with iRoot SP.
Ultrafast Laser Fabrication of Hybrid Micro‐ and Nano‐Structures in Semiconductor‐doped Borosilicate Glasses
Authors: Mardilovich Pavel , Fletcher Luke B. , Troy Neil W. , Yang Lihmei , Huang Huan , Risbud Subhash H. , Krol Denise M.
Published: April 2013

Femtosecond (fs)‐laser processing of CdSxSe1‐x‐doped borosilicate glasses was investigated to create hybrid multiscale structures consisting of semiconductor nanocrystals embedded in microscopic domains defined by the laser irradiation. Laser processing was carried out with both low (1 KHz) and high (1 MHz) repetition rate fs‐lasers using pulse fluences between 2 and 2000 J/cm2 and sample scan speeds ranging from 0.05 to 4 mm/s. The samples were subsequently heat‐treated at temperatures between 500 and 600°C and characterized using optical microscopy, electron microscopy, wave dispersive x‐ray spectroscopy (WDS), and confocal fluorescence microscopy. For 1‐KHz laser processing conditions, nanocrystal precipitation showed no significant distinction between the modified and unmodified regions in the sample. Using a 1‐MHz pulse repetition rate laser, however, we introduced chemical inhomogeneity across microscopic modifications, forming three chemically distinct regions: sodium and potassium‐rich, zinc rich, and silicon rich. These regions exhibited different semiconductor precipitation dynamics, with the sodium and potassium‐rich region showing strong preferential precipitation of cadmium sulfo‐selenide nanoparticles, thereby localizing quantum dot precipitation to these chemically defined microcrucibles in the glass.
Evaluative choices and rhetorical impact:American learners ofPersian as a foreign language writing to appraise
Authors: Abasi Ali R.
Published: April 2013

graphic
Identification and biochemical characterization of Laodelphax striatellus neutral ceramidase
Authors: Zhou Y. , Lin X.‐W. , Zhang Y.‐R. , Huang Y.‐J. , Zhang C.‐H. , Yang Q. , Li H.‐Y. , Yuan J.‐Q. , Cheng J.‐A. , Xu R. , Mao C. , Zhu Z.‐R.
Published: April 2013

Ceramidases are a group of enzymes that catalyse hydrolysis of ceramides to generate fatty acid and sphingosine. In this study, we report the cloning and characterization of the rice small brown planthopper Laodelphax striatellus neutral ceramidase (nCDase), LsnCer. LsnCer was identified by sequencing the transcriptome of L. striatellus and is a protein of 717 amino acids with a predicted molecular weight of 79.3 kDa. Similarly to other known nCDases, the optimum pH for LsnCer is 8.0 and the optimum temperature is 37 °C for its in vitro activity. LsnCer activity is inhibited by Zn2+ significantly and Fe2+ slightly. LsnCer has broad substrate specificity with a preference for ceramides with a medium acyl‐chain or a monounsaturated long acyl‐chain. Infection with rice strip virus (RSV) or treatment with insecticides significantly increased LsnCer mRNA expression and its enzymatic activity in L. striatellus. These results suggest that LsnCer is a bona fide nCDase that may have a role in adaption of L. striatellus to environmental stresses.
Polish Contemporary Migration: From Co‐migrants to Project ME
Authors: Isański Jakub , Mleczko Agata , Eid Renata Seredyńska‐Abou
Published: April 2013

International migration mirrors contemporary society in all its complexity. What has not changed for centuries is the principal motif: people leave their country of origin hoping for a better life. Poland has a long history of emigration: Poles have been migrating for more than 200 years for political, economic and social reasons. In recent decades, Polish migration patterns have undergone dramatic changes. Using online survey data, this article explores new trends in Polish migration since the country's accession to the European Union in 2004. The survey was focused on Polish migrants who stayed abroad for some time, those who stayed abroad before the accession, those who returned to Poland or those who experienced multiple travels and have an ongoing migration project.

We conclude that new trends have emerged among Polish migrants. Contemporary migrants are aware of the benefits related to migration and are capable of implementing their migration project quite skilfully. Their high susceptibility to the economic setting proves their flexibility. Polish migrants highly value their new lifestyle abroad and consider friends their most important source of support.
Image cytometer method for automated assessment of human spermatozoa concentration
Authors: Egeberg D. L. , Kjærulff S. , Hansen C. , Petersen J. H. , Glensbjerg M. , Skakkebæk N. E. , Jørgensen N. , Almstrup K.
Published: April 2013

In the basic clinical work‐up of infertile couples, a semen analysis is mandatory and the sperm concentration is one of the most essential variables to be determined. Sperm concentration is usually assessed by manual counting using a haemocytometer and is hence labour intensive and may be subjected to investigator bias. Here we show that image cytometry can be used to accurately measure the sperm concentration of human semen samples with great ease and reproducibility. The impact of several factors (pipetting, mixing, round cell content, sperm concentration), which can influence the read‐out as well as inter‐operator and ‐cytometer variation on two different image cytometers (NC‐3000 and SP‐100) were evaluated. Furthermore, 725 semen samples were assessed both by manual assessment (WHO recommended method) and by image cytometry and tight correlations between the measured concentrations were shown. Moreover, by evaluation of repeated measurements it appeared that image cytometry produced more consistent and accurate measurements than manual counting of human spermatozoa concentration. In conclusion, image cytometry provides an appealing substitute of manual counting by providing reliable, robust and easy measurement of human sperm concentration.
Retrograde ejaculation and sexual dysfunction in men with diabetes mellitus: a prospective, controlled study
Authors: Fedder J. , Kaspersen M. D. , Brandslund I. , Højgaard A.
Published: April 2013

Retrograde ejaculation (RE) and erectile dysfunction may be caused by diabetes mellitus (DM), but the prevalence of RE among DM patients is unknown. A prospective, blinded case–control study comparing men with DM with matched controls according to RE and erectile dysfunction was performed. Twenty‐seven men with DM matched the inclusion criteria and agreed to participate in the study, and of these 26 delivered an ejaculate. We were able to recruit 18 matching controls, and of these 16 delivered an ejaculate.

Nine of 26 men with DM who delivered an ejaculate had RE, whereas none of 16 controls had RE (p < 0.01). The mean duration of DM was longer for DM patients with RE (20 years) compared with DM patients in whom RE could not be demonstrated (13 years), but the difference was not statistically significant. RE could not be associated with BMI, waist circumference, blood pressure, Haemoglobin A1c (HgbA1c), high‐density lipoprotein HDL cholesterol, triglycerides, fasting glucose, or s‐testosterone. Diabetics suffering from RE more frequently exhibited erectile dysfunction compared with non‐diabetics and diabetics without RE, and the last‐mentioned group again more frequently than controls. These findings could not be explained by use of antihypertensive drugs.

Whereas none of the included control participants showed signs of abnormal ejaculation, every third man with DM exhibited retrograde ejaculation. It is important to be aware of this association, and that post‐ejaculatory urine is routinely analysed from aspermic fertility clinic attendants and diabetics with low ejaculate volumes.