bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Methods of Correcting for Multiple Comparisons Implemented in SPM12 in Social Neuroscience fMRI Studies: An Example from Moral Psychology
Authors: Han Hyemin , Glenn Andrea L.
Published: April 2017

In fMRI research, the goal of correcting for multiple comparisons is to identify areas of activity that reflect true effects, and thus would be expected to replicate in future studies. Finding an appropriate balance between trying to minimize false positives (Type I error) while not being too stringent and omitting true effects (Type II error) can be challenging. Furthermore, the advantages and disadvantages of these types of errors may differ for different areas of study. In many areas of social neuroscience that involve complex processes and considerable individual differences, such as the study of moral judgment, effects are typically smaller and statistical power weaker, leading to the suggestion that less stringent corrections that allow for more sensitivity may be beneficial, but also result in more false positives. Using moral judgment fMRI data, we evaluated four commonly used methods for multiple comparison correction implemented in SPM12 by examining which method produced the most precise overlap with results from a meta-analysis of relevant studies and with results from nonparametric permutation analyses. We found that voxel-wise thresholding with family-wise error correction based on Random Field Theory provides a more precise overlap (i.e., without omitting too few regions or encompassing too many additional regions) than either clusterwise thresholding, Bonferroni correction, or false discovery rate correction methods.
Using Neural Networks to Improve Single Cell RNA-Seq Data Analysis
Authors: Lin Chieh , Jain Siddhartha , Kim Hannah , Bar-Joseph Ziv
Published: April 2017

While only recently developed, the ability to profile expression data in single cells (scRNA-Seq) has already led to several important studies and findings. However, this technology has also raised several new computational challenges including questions related to handling the noisy and sometimes incomplete data, how to identify unique group of cells in such experiments and how to determine the state or function of specific cells based on their expression profile. To address these issues we develop and test a method based on neural networks (NN) for the analysis and retrieval of single cell RNA-Seq data. We tested various NN architectures, some biologically motivated, and used these to obtain a reduced dimension representation of the single cell expression data. We show that the NN method improves upon prior methods in both, the ability to correctly group cells in experiments not used in the training and the ability to correctly infer cell type or state by querying a database of tens of thousands of single cell profiles. Such database queries (which can be performed using our web server) will enable researchers to better characterize cells when analyzing heterogeneous scRNA-Seq samples.

Supporting website:http://sb.cs.cmu.edu/scnn/

Password for accessing the retrieval task webserver: scRNA-Seq
Quantitative assessment of cell fate decision between autophagy and apoptosis
Authors: Liu Bing , Oltvai Zoltán N. , Bayir Hulya , Silverman Gary A. , Pak Stephen C. , Perlmutter David H. , Bahar Ivet
Published: April 2017

Autophagy and apoptosis regulate cell survival and death, and are implicated in the pathogenesis of many diseases. The same type of stress signals can induce either process, but it is unclear how cells ‘assess’ cellular damage and make a ‘life’ or ‘death’ decision by activating autophagy or apoptosis. A computational model of coupled apoptosis and autophagy is built here to study the systems-level dynamics of the underlying signaling network. The model explains the differential dynamics of autophagy and apoptosis in response to various experimental stress signals. Autophagic response dominates at low-to-moderate stress; whereas the response shifts from autophagy (graded activation) to apoptosis (switch-like activation) with increasing intensity of stress. The model reveals that this dynamic cell fate decision is conferred by a core regulatory network involving cytoplasmic Ca2+as a rheostat that fine-tunes autophagic and apoptotic responses. A G-protein signaling-mediated feedback loop maintains cytoplasmic Ca2+level, which in turn governs autophagic response through an AMP-activated protein kinase (AMPK)-mediated feedforward loop. The model identified Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ) as a determinant of the opposite roles of cytoplasmic Ca2+in autophagy regulation. The results also demonstrated that the model could contribute to the development of pharmacological strategies modulate cell fate decisions.
Matrix production inBacillus subtilisbiofilms is localized to a propagating front
Authors: Srinivasan Siddarth , Vladescu Ioana D. , Koehler Stephan A. , Wang Xiaoling , Mani Madhav , Rubinstein Shmuel M.
Published: April 2017

Bacterial biofilms are surface attached microbial communities encased in self-produced extracellular polymeric substances (EPS). Development of a mature biofilm must require coordinating cell differentiation and multicellular activity at scales much larger than the single microbial unit. Here we demonstrate that during development ofBacillus subtilisbiofilms, EPS matrix production is localized to a front propagating at the periphery. We show that within the front, cells switch off matrix production and transition to sporulation after a set time delay of∼100 min. Correlation analyses of fluctuations in fluorescence reporter activity reveals that the front emerges from a pair of gene expression waves of matrix production and sporulation. The expression waves travel across cells that are immobilized in the biofilm matrix, in contrast to active cell migration or horizontal colony spreading. A single length scale and time scale couples the spatiotemporal propagation of both fronts throughout development, with the front displacement obeying at1/2scaling law. As a result, gene expression patterns within the advancing fronts collapse to self-similar expression profiles. Our results indicate that development of bacterial biofilms may be governed by universal wave-like dynamics localized to a self-similar front.
The good, the bad, and the ugly in the melting pot
Authors: George Olusoji , Yusuff Kolawole M. , Cornelius Nelarine
Published: April 2017

Purpose

Taking a clue from the aftermaths of colonisation and the need to manage an “unholy marriage” created by the British colonial masters, the purpose of this paper is to examine the peculiar challenges of managing Nigeria’s unique diversity in the public sector through the critical lens of the Federal Character Principle (FCP) with specific focus on how this invented model of diversity management ended up creating more serious problems than it was meant to solve in the Nigerian public administration.

Design/methodology/approach

The paper is essentially a review, and it relies on previous studies and real-world evidence on the subject. The paper systematically traces the evolution of diversity management in Nigerian public administration through the critical lens of the FCP with specific focus on how problematic it is to management Nigeria’s unique diversity with more serious problems being created by the FCP application in the public sector.

Findings

The paper reveals that the constitutional provisions of the “Federal Character Principle” ended up in creating more problems than it set out to solve, reflecting in the “melting pot” allegory. It reveals how problematic it is to manage the country’s diversity, and highlights some of the problems created by the FCP. The review makes a case for an urgent need to intensify empirical research on the subject in order to fashion out a better way of managing Nigeria’s diversity in the public sector.

Research limitations/implications

One major limitation of this paper is rooted in lack of empirical research such as survey to further explore the topic. Few real life examples and cases provided are considered insufficient to justify some of the assertions. Thus, a call for more systematic and empirical research is made.

Practical implications

The implication of the finding is that the model for managing workforce diversity especially in the Nigerian public sector (not limited to the public administration) must be “Nigerianised” such that the unique socio-cultural realities of the Nigeria’s society as well as benefits accrued to diversity can be fully explored in driving the growth of the country and survival of the “unity-in-diversity” goal.

Originality/value

The paper will benefit the government, all stakeholders, and the Nigerian society at large. It offers some useful insights into public administration. It stimulates an interest to conduct further research on diversity management with a view to producing some useful findings that could lead to a better management of diversity in the country.
The technology foresight system of the Russian Federation: a systemic view
Authors: Kuzminov Ilya F. , Thurner Thomas , Chulok Alexander
Published: April 2017

Purpose

This paper aims to describe and discuss the architecture of Russia’s Technology Foresight System (TFS). This paper introduces the reader to the integration of the TFS into the public administration system and, specifically, into the national strategic planning system.

Design/methodology/approach

To do so, the authors fall back on more than 10 years of experience in performing foresight exercises for Russian policy makers of their institution.

Findings

Thereby, the paper highlights the implications arising from the interaction between sectoral and national components of TFS and on application of the results of foresight studies (implemented within the framework of TFS) for the strategic planning.

Originality/value

Russia has a long history of technological planning and forecasting and engages regularly in extensive foresight activities of both national and sectoral relevance. Also, Russia’s leadership repeatedly stresses the importance of such foresight activities which are outlined by a national law since 2014.
Diversity management in tourism and hospitality: an exploratory study
Authors: Malik Ruchika , Madappa Tanavi , Chitranshi Jaya
Published: April 2017

Purpose

The hospitality and tourism industry has seen an increase in organizations operating internationally, bringing people from diverse cultural backgrounds together. The authors aim to help clarify that with a lack of awareness and understanding about diversity, many problems arise in terms of effective intercultural communication between managers and employees and employees and the customers. This paper helps in answering the questions related to the importance of cross cultural management, the intercultural issues faced by an organization, the best practices for diversity management and the future of cultural diversity.

Design/methodology/approach

The authors have carried out a review-based research of 60 papers relevant to the topic. The study has been restricted to secondary data consisting of research in the area of managing cultural diversity.

Findings

The researchers have concluded that there are different dimensions of cultural diversity and thus policies and programs to manage it have to be carefully implemented and integrated. Also, managers need to identify the current gaps in the organization in terms of diversity management to take the necessary steps for building a harmonious relationship between expatriates and the local employees.

Originality/value

The study addresses the complex nature of cultural diversity and the management issues of multiculturalism within the hospitality and tourism industry. The authors have made an effort to identify the best practices and programs for managing a diverse workforce which may also improve engagement and retention levels through radical inclusion of employees.
Professional development of sustainability competences in higher education
Authors: Lambrechts Wim , Verhulst Elli , Rymenams Sara
Published: April 2017

Purpose

This paper aims to provide insights into the relation between professional development (PD) and organisational change processes towards sustainability, with a specific focus on empowerment.

Design/methodology/approach

The paper builds upon a constructivist approach, combining a literature review, a desk research on key publications and reports and a socio-political analysis to reveal the specific context in Flanders, Belgium. Findings are then connected to earlier insights from research on organisational change for sustainability.

Findings

The paper provides a number of PD initiatives that focus on sustainability in general and in a single higher education (HE) institution. Framing such initiatives as an organisational change process offers insights on how elements of empowerment are currently incorporated in PD initiatives and how it can strengthen them to lead to the further integration of sustainability competences in HE.

Research limitations/implications

Limitations are linked with the kind of sources used in the constructivist approach. The analysis only looks at written reports on the topic, albeit it also builds upon the first-hand experiences of educators in the HE institution focused upon in the case.

Practical implications

There is a need to frame PD initiatives as an organisational change process towards sustainability with specific attention towards empowerment. Without this framing, PD approaches comprise the risk of being left in the margins or being understood as single initiatives without any connection to the bigger picture, i.e. the transition towards sustainability in HE.

Social implications

Interlinking PD and organisational change provides opportunities to frame the sustainability transition within the university in a wider societal context.

Originality/value

The paper provides an original contribution to the debate on sustainability competences, as it frames the PD within an organisational context, rather than focusing on the individual role of educators.
Engaging teacher educators with the sustainability agenda
Authors: Amado Addise , Dalelo Aklilu , Adomßent Maik , Fischer Daniel
Published: April 2017

Purpose

There is broad consensus that the implementation of education for sustainable development (ESD) requires the consideration of geographical and cultural contexts. Despite such an agreement at a theoretical level, there is so far an apparent lack of practical experiences and solid research on approaches that effectively manage to engage professional educators in higher education with ESD in the context of a developing country from the Global South. This paper aims to address this gap and present a case study from a pilot professional development program (PDP) that sought to implement and mainstream ESD among Ethiopian colleges of teacher education (CTEs) and theological seminaries (TSs).

Design/methodology/approach

The research presented is based on the methodology of evaluative case study research in ESD. It analyzes the PDP’s specific objectives with regard to capacity and structure building, describes major activities implemented and how these relate to the objectives and explores major outcomes of the PDP.

Findings

The paper presents a comprehensive training curriculum aimed at addressing ESD in Ethiopian CTEs and TSs in a whole-institution approach. Results suggest that the PDP’s approach to combine human capacity and institutional structure building was effective in supporting the implementation and mainstreaming of ESD in CTEs and TSs in Ethiopia.

Originality/value

This case study presents original research on a pilot Ethiopian PDP that was implemented in collaboration with two academic institutions from Ethiopia and Germany.
Training sessions fostering transdisciplinary collaboration for sustainable development
Authors: Meyer Jonas , Mader Marlene , Zimmermann Friedrich , Çabiri Ketrina
Published: April 2017

Purpose

The purpose of this paper is to examine sustainability-related challenges in the two Western Balkan countries – Albania and Kosovo. It discusses the opportunities of local higher education institutions (HEIs) taking responsibility to tackle these challenges by providing professional development through science–society collaboration in innovative training sessions for university educators.

Design/methodology/approach

A literature review on actual challenges and transformations of higher education for sustainable development (ESD) in Albania and Kosovo will be the starting point of this paper. Subsequently, experiences from the on-going European Union (EU) project “ConSus” will be used to draw both a competence framework for ESD within science–society collaboration based on the training sessions, as well as possible scaling opportunities.

Findings

The paper draws possible approaches of training sessions for university educators promoting sustainable development and science–society collaboration in higher education. They will be concluded by addressing possible scaling opportunities of the project’s activities.

Practical implications

The experiences of the ConSus training sessions will outline competences of university educators in ESD gained in relation to transdisciplinary collaboration in research and teaching.

Originality/value

The paper will contribute to ESD approaches in higher education in Albania and Kosovo. Furthermore, scaling possibilities will be discussed to systematically implement ESD approaches also in higher hierarchical levels and other HEIs.
Research involving people with dementia: a literature review
Authors: Rivett Emma
Published: April 2017

Purpose

The purpose of this paper is to review existing literature that addresses involving people with dementia in research, and how this can relate to involving people with dementia in research as co-researchers.

Design/methodology/approach

The approach takes the form of a literature review.

Findings

Despite a growing drive for patient and public involvement in research, people with dementia are often still excluded from many areas of research, and are rarely given the opportunity to act as co-researchers. Existing principles focussing on how people with dementia can effectively and safely be involved in research as participants (including ethical considerations, enabling participation, support for people with dementia and the involvement of family members and carers) can also be applied to enabling people with dementia to be actively involved with research as co-researchers. The benefits of involving people with dementia in research are also explored.

Originality/value

This paper adds to the small body of literature that addresses involving people with dementia in research as co-researchers, and advocates for ongoing research and development in this area.
The effects of climate warming and disturbance on the colonization potential of ornamental alien plant species
Authors: Haeuser Emily , Dawson Wayne , van Kleunen Mark
Published: April 2017

A large number of alien plant species have been introduced as ornamental garden plants to Europe, but relatively few have become invasive. Low climatic suitability may be limiting the current invasion potential of many alien ornamental species. However, with ongoing disturbance and climate change, this barrier may be reduced for some species.

Here, we tested how colonization ability (a prerequisite for invasion) of frequently planted alien ornamentals depends on disturbance and heating, and on their species characteristics. We sowed seeds of 37 non‐naturalized alien herbaceous garden‐plant species into native grassland plots with and without disturbance, and with and without infrared‐heating lamps. To assess whether their responses differ from those within the regional wild flora, we also sowed 14 native species and 12 naturalized alien species. During 2 years, we assessed the likelihoods of germination, first‐year survival, second‐year survival and flowering of these 63 study species.

The heating treatment, which also reduced soil moisture, decreased all measures of colonization success, but more so for sown native species than for the non‐naturalized and naturalized alien ones. The disturbance treatment increased colonization success, and because heating decreased productivity of the undisturbed grassland plots, it also increased invasibility of these plots. Average colonization success of non‐naturalized aliens was reduced by heating, but some species were not affected or performed even better with heating, particularly those with an annual life span and a high seed mass. Winter hardiness improved colonization ability of non‐naturalized aliens, but this advantage was reduced in the heated plots.

Synthesis. Disturbance increased and heating decreased the absolute colonization success of most of the 63 species sown. However, heating had stronger adverse effects on the resident grassland and sown native species than either type of sown alien species. Together, these results suggest that some alien plants may have greater colonization success relative to native plants under a warmer climate.
Measuring the quality of Hospital Food Services: Development and reliability of a Meal Quality Audit Tool
Authors: Banks Merrilyn , Hannan‐Jones Mary , Ross Lynda , Buckley Ann , Ellick Jennifer , Young Adrienne
Published: April 2017

Aim

To develop and test the reliability of a Meal Quality Audit Tool (MQAT) to audit the quality of hospital meals to assist food service managers and dietitians in identifying areas for improvement.

Methods

The MQAT was developed using expert opinion and was modified over time with extensive use and feedback. A phased approach was used to assess content validity and test reliability: (i) trial with 60 dietetic students, (ii) trial with 12 food service dietitians in practice and (iii) interrater reliability study. Phases 1 and 2 confirmed content validity and informed minor revision of scoring, language and formatting of the MQAT. To assess reliability of the final MQAT, eight separate meal quality audits of five identical meals were conducted over several weeks in the hospital setting. Each audit comprised an ‘expert’ team and four ‘test’ teams (dietitians, food services and ward staff). Interrater reliability was determined using intra‐class correlation analysis.

Results

There was statistically significant interrater reliability for dimensions of Temperature and Accuracy (P < 0.001) but not for Appearance or Sensory. Composition of the ‘test’ team appeared to influence results for Appearance and Sensory, with food service‐led teams scoring higher on these dimensions. ‘Test’ teams reported that MQAT was clear and easy to use.

Conclusions

MQAT was found to be reliable for Temperature and Accuracy domains, with further work required to improve the reliability of the Appearance and Sensory dimensions. The systematic use of the tool, used in conjunction with patient satisfaction, could provide pertinent and useful information regarding the quality of food services and areas for improvement.
Ventilation via the 2.4 mm internal diameter Tritube® with cuff – new possibilities in airway management
Authors: Kristensen M. S. , de Wolf M. W. P. , Rasmussen L. S.
Published: April 2017

Background

A small tube may facilitate tracheal intubation and improve surgical access. We describe our initial experience with the Tritube® that is a novel cuffed endotracheal tube with a 2.4 mm internal diameter.

Methods

The Tritube® was used in seven adult Ear‐Nose‐and Throat surgical patients with airway narrowing or whose surgical access was facilitated by this small‐bore endotracheal tube. Ventilation through Tritube® is performed with the manually operated Ventrain®‐ventilator that allows active suctioning during expiration, therefore facilitating normoventilation through small diameter airways.

Results

The small diameter of Tritube® seemed to improve glottis visualisation during intubations and gave excellent working conditions for surgery. Two patients were intubated awake with a flexible scope and a guide wire or with an angulated video laryngoscope. One patient had almost complete glottic occlusion that just allowed for passage of the Tritube®. Adequate ventilation was achieved in all patients and intratracheal pressure was kept between 5 and 20 cm H2O. The tube was well tolerated after emergence from anaesthesia and kept intratracheally in five awake patients in the post‐operative recovery unit, in one case for more than 1 h. Ventilating with Ventrain® through Tritube® demands meticulous breath by breath measurement and adjustment of the intratracheal pressure.

Conclusion

The 2.4 mm internal diameter Tritube® seems to facilitate tracheal intubation and to provide unprecedented view of the intubated airway during oral, pharyngeal, laryngeal or tracheal procedures in adults. This technique has the potential to replace temporary tracheostomy, jet‐ventilation or extra‐corporal membrane oxygenation in selected patients.
How do ‘busy’ and ‘overlap’ directors relate to CEO pay structure and incentives?
Authors: Pathan Shams , Wong Peh Hwa , Benson Karen
Published: April 2017

We examine how CEO compensation is affected by the presence of busy and overlap directors. We find that CEOs at firms with more busy directors receive greater total pay, fixed salary and equity‐linked pay and exhibit higher pay‐performance (delta) and pay‐risk (vega) sensitivities. Our results also suggest that CEOs at firms with more overlap directors take smaller total pay and equity‐linked pay and reveal lower delta and vega. We further show that the impact of busy and overlap directors on CEO pay is more visible for firms with less complexity and low information acquisition cost.
Dopamine D1 or D2 receptor‐expressing neurons in the central nervous system
Authors: Wei Xiaoyan , Ma Tengfei , Cheng Yifeng , Huang Cathy C.Y. , Wang Xuehua , Lu Jiayi , Wang Jun
Published: April 2017

Dopamine signals mainly through D1 receptors (D1Rs) and D2 receptors (D2Rs); D1R‐expressing or D2R‐expressing neurons contribute to distinct reward and addictive behaviors. Traditionally, transgenic mice expressing green fluorescent protein (GFP) under D1R or D2R promoters are used for fluorescent verification in electrophysiology studies, whereas Cre mice are employed for behavioral research. However, it is unknown whether the same neuronal populations are targeted in GFP and Cre mice. Additionally, while D1Rs and D2Rs are known to be expressed in different striatal neurons, their expression patterns outside the striatum remain unclear. The present study addressed these two questions by using several transgenic mouse lines expressing fluorescent proteins (GFP or tdTomato) or Cre under the control of D1R or D2R promoters. We found a high degree of overlap between GFP‐positive and Cre‐positive neurons in the striatum and hippocampus. Additionally, we discovered that D1Rs and D2Rs were highly segregated in the orbitofrontal cortex, prefrontal cortex, dorsal and ventral hippocampus, and amygdala: ~4–34 percent of neurons co‐expressed these receptors. Importantly, slice electrophysiological studies demonstrated that D1R‐positive and D1R‐negative hippocampal neurons were functionally distinct in a mouse line generated by crossing Drd1a‐Cre mice with a Cre reporter Ai14 line. Lastly, we discovered that chronic alcohol intake differentially altered D1R‐positive and D2R‐positive neuron excitability in the ventral CA1. These data suggest that GFP and Cre mice target the same populations of striatal neurons, D1R‐expressing or D2R‐expressing neurons are highly segregated outside the striatum, and these neurons in the ventral hippocampal may exert distinct roles in alcohol addiction.
African wolf diet, predation on livestock and conflict in the Guassa mountains of Ethiopia
Authors: Atickem Anagaw , Simeneh Getachew , Bekele Afework , Mekonnen Tariku , Sillero‐Zubiri Claudio , Hill Russell A. , Stenseth Nils Chr.
Published: April 2017

The African wolf (Canis lupus lupaster) was first identified in 2011 in the Ethiopian highlands, with its status as a new species confirmed in 2015. We studied the diet of a confirmed African wolf population in the Menz‐Guassa Community Conservation Area of central Ethiopia from scat samples collected by den sites from August to November 2010. Rodents were found to be the principal food items occurring in 88.1% of scats (n = 101), followed by plant material (34.7%) and insects (21.8%). Information on reported livestock predation and ensuing conflict with the agro‐pastoral community was obtained through a questionnaire survey. Interview respondents listed the African wolf as the most serious predator of livestock, accounting for 74.6% of the reported kills (n = 492) and 78.9% of the economic loss. Over 70% of reported livestock predation occurred during the dry season (January–April). Better livestock management during this period may significantly reduce conflict. As sympatric Ethiopian wolves primarily feed on rodents, further studies on the foraging ecology, niche overlap and interspecific interactions between the two species should be studied to determine the extent of competition between the two species.
Autonomic Receptor‐mediated Regulation of Production and Release of Nitric Oxide in Normal and Malignant Human Urothelial Cells
Authors: Winder Michael , Vesela Renata , Aronsson Patrik , Patel Bhavik , Carlsson Thomas
Published: April 2017

In the urinary bladder, the main source of NO seems to be the urothelium and the underlying suburothelium. In this study, we aimed to characterize how receptors in the human urothelium regulate the production and release of NO. For this, we cultured two human urothelial cell lines – the normal immortalized cell line UROtsa and the malignant cell line T24. These were treated with an array of agonists and antagonists with affinity for adrenergic, muscarinic and purinergic receptors. The production of NO and expression of nitric oxide synthase (NOS) was studied by immunocytochemistry and Western blotting. The amount of released NO was measured indirectly by detecting nitrite using amperometry and a Griess reaction kit. The results showed that NO, endothelial NOS and inducible NOS were predominantly produced and expressed in the close vicinity of the nucleus in untreated human urothelial cells. Upon treatment with a beta‐adrenoceptor agonist, but not any of the other agonists or antagonists, the pattern of NO production changed, showing a more even production throughout the cytosol. The pattern of expression of endothelial NOS changed in a similar way upon dobutamine treatment. The release of nitrite, as a measurement of NO, increased after treatment with dobutamine from 0.31 ± 0.029 to 1.97 ± 0.18 nmol and 0.80 ± 0.12 to 3.27 ± 0.24 nmol in UROtsa and T24, respectively. In conclusion, our results show that the expression of NOS and production of NO as well as the release of NO from human urothelial cells is regulated by beta‐adrenoceptor activation.
Semiparametric Probit Models with Univariate and Bivariate Current-status Data
Authors: Liu Hao , Qin Jing
Published: April 2017

Multivariate current-status data are frequently encountered in biomedical and public health studies. Semiparametric regression models have been extensively studied for univariate current-status data, but most existing estimation procedures are computationally intensive, involving either penalization or smoothing techniques. It becomes more challenging for the analysis of multivariate current-status data. In this article, we study the maximum likelihood estimations for univariate and bivariate current-status data under the semiparametric probit regression models. We present a simple computational procedure combining the expectation–maximization algorithm with the pool-adjacent-violators algorithm for solving the monotone constraint on the baseline function. Asymptotic properties of the maximum likelihood estimators are investigated, including the calculation of the explicit information bound for univariate current-status data, as well as the asymptotic consistency and convergence rate for bivariate current-status data. Extensive simulation studies showed that the proposed computational procedures performed well under small or moderate sample sizes. We demonstrate the estimation procedure with two real data examples in the areas of diabetic and HIV research.
Impact of preoperative risk on metastatic progression and cancer‐specific mortality in patients with adverse pathology at radical prostatectomy
Authors: Boehm Katharina , Leyh‐Bannurah Sami‐Ramzi , Rosenbaum Clemens , Brandi Laurenz S. , Budäus Lars , Graefen Markus , Huland Hartwig , Haferkamp Axel , Tilki Derya
Published: April 2017

Objective

To evaluate the impact of preoperative risk category on metastatic disease and prostate cancer‐specific mortality (CSM) in patients with prostate cancer (PCa) with adverse pathology at radical prostatectomy (RP).

Patients and Methods

The records of 6 943 patients who underwent RP at a European tertiary centre were analysed. Biochemical recurrence (BCR), metastatic disease and CSM were assessed for patients with adverse pathology at RP, and stratified according to preoperative low‐ vs intermediate‐/high‐risk PCa groups. Kaplan–Meier, cumulative incidence, Cox regression and competing risk regression analyses were performed.

Results

In patients with extracapsular extension, the metastatic disease rate was 1.6% vs 8% (P < 0.001) and the CSM rate was 2% vs 5% (P = 0.041) for low vs intermediate‐/high‐risk patients, respectively, at 10 years. In patients with pathological Gleason score ≥3+4, the metastatic disease rate was 3.0% vs 12% (P < 0.001) and the CSM rate was 3% vs 8%, respectively (P < 0.001). In patients with positive surgical margins (PSMs), the metastatic disease rate was 2.9% vs 15% (P < 0.001) and the CSM rate was 4% vs 10%, respectively (P = 0.0001). Low‐risk status was a predictive factor for metastatic disease in patients with pathological Gleason score ≥3+4 (hazard ratio [HR] 0.51), pathological Gleason score ≥4+3 (HR 0.41) and PSMs (HR 0.46) and was a predictive factor for CSM risk in patients with pathological Gleason score ≥3+4 (HR 0.62).

Conclusions

Patients with low‐risk PCa were at significantly lower risk of metastatic disease and CSM than their intermediate‐/high‐risk counterparts, when adverse pathological features were identified at RP. This should be emphasized in the decision‐making process after RP.
Men's Eating and Living (MEAL) study (CALGB 70807 [Alliance]): recruitment feasibility and baseline demographics of a randomized trial of diet in men on active surveillance for prostate cancer
Authors: Parsons J. Kellogg , Pierce John P. , Mohler James , Paskett Electra , Jung Sin‐Ho , Morris Michael J. , Small Eric , Hahn Olwen , Humphrey Peter , Taylor John , Marshall James
Published: April 2017

Objective

To assess the feasibility of performing national, randomized trials of dietary interventions for localized prostate cancer.

Methods

The Men's Eating and Living (MEAL) study (CALGB 70807 [Alliance]) is a phase III clinical trial testing the efficacy of a high‐vegetable diet to prevent progression in patients with prostate cancer on active surveillance (AS). Participants were randomized to a validated diet counselling intervention or to a control condition. Chi‐squared and Kruskal–Wallis analyses were used to assess between‐group differences at baseline.

Results

Between 2011 and 2015, 478 (103%) of a targeted 464 patients were randomized at 91 study sites. At baseline, the mean (sd) age was 64 (6) years and mean (sd) PSA concentration was 4.9 (2.1) ng/mL. Fifty‐six (12%) participants were African‐American, 17 (4%) were Hispanic/Latino, and 16 (3%) were Asian‐American. There were no significant between‐group differences for age (P = 0.98), race/ethnicity (P = 0.52), geographic region (P = 0.60), time since prostate cancer diagnosis (P = 0.85), PSA concentration (P = 0.96), clinical stage (T1c or T2a; P = 0.27), or Gleason sum (Gleason 6 or 3+4 = 7; P = 0.76). In a pre‐planned analysis, the baseline prostate biopsy samples of the first 50 participants underwent central pathology review to confirm eligibility, with an expectation that <10% would become ineligible. One of 50 participants (2%) became ineligible.

Conclusion

The MEAL study shows the feasibility of implementing national, multi‐institutional phase III clinical trials of diet for prostate cancer and of testing interventions to prevent disease progression in AS.
European Section of Urotechnology educational video on fluoroscopic‐guided puncture in percutaneous nephrolithotomy: all techniques step by step
Authors: Kyriazis Iason , Liatsikos Evangelos , Sopilidis Odysseas , Kallidonis Panagiotis , Skolarikos Andreas ,   the European Section of Urotechnology (ESUT)
Published: April 2017

Objective

To describe the most common fluoroscopic‐guided access techniques during percutaneous nephrolithotomy (PCNL) in a step‐by‐step manner and to assist in the standardisation of their technique and terminology.

Methods

A high‐quality animation video was created for each of the respective fluoroscopic techniques, focusing into the parallel projection of external surgical manoeuvres and their effect in the three‐dimensional space of the kidney.

Results

Four predominant fluoroscopic‐guided percutaneous access techniques are available, each with different advantages and limitations. Monoplanar access is used when a stable single‐axis fluoroscopic generator is available and is mostly based on surgeons’ experience. Biplanar access uses a second fluoroscopy axis to assess puncture depth. The ‘bull's eye’ technique follows a coaxial to fluoroscopy puncture path and is associated with a shorter learning curve at the cost of increased hand radiation exposure. Hybrid and conventional triangulate techniques use target projection by two fluoroscopic planes to define the exact localisation of the target in space and access it through a third puncture site.

Conclusions

Fluoroscopic guidance during PCNL puncture is a very efficient method for access establishment. The percutaneous surgeon should be familiar with all available variations of fluoroscopic approach in order to be prepared to adapt puncture technique for any given scenario.
Strong influences of a dominant, ground‐nesting ant on recruitment, and establishment of ant colonies and communities
Authors: Ennis Katherine K. , Philpott Stacy M.
Published: April 2017

Many factors drive the organization of communities including environmental factors, dispersal abilities, and competition. In particular, ant communities have high levels of interspecific competition and dominance that may affect community assembly processes. We used a combination of surveys and nest supplementation experiments to examine effects of a dominant ground‐nesting ant (Pheidole synanthropica) on (1) arboreal twig‐nesting, (2) ground‐foraging, and (3) coffee‐foraging ant communities in coffee agroecosystems. We surveyed these communities in high‐ and low‐density areas of P. synanthropica over 2 years. To test for effects on twig ant recruitment, we placed artificial nesting resources on coffee plants in areas with and without P. synanthropica. The first sampling period revealed differences in ant species composition on the ground, in coffee plants, and artificial nests between high‐ and low‐density sites of P. synanthropica. High‐density sites also had significantly lower recruitment of twig ants and had species‐specific effects on twig ant species. Prior to the second survey period, abundance of P. synanthropica declined in the high‐density sites, such that P. synanthropica densities no longer differed. Subsequent sampling revealed no difference in total recruitment of twig ants to artificial nests between treatments. Likewise, surveys of ground and coffee ants no longer showed significant differences in community composition. The results from the first experimental period, followed by survey results after the decline in P. synanthropica densities suggest that dominant ants can drive community assembly via both recruitment and establishment of colonies within the community.
Genetic variation at the Th2 immune gene IL13 is associated with IgE‐mediated paediatric food allergy
Authors: Ashley S. E. , Tan H.‐T. T. , Peters R. , Allen K. J. , Vuillermin P. , Dharmage S. C. , Tang M. L. K. , Koplin J. , Lowe A. , Ponsonby A.‐L. , Molloy J. , Matheson M. C. , Saffery R. , Ellis J. A. , Martino D. ,   the HealthNuts team
Published: April 2017

Background

Food allergies pose a considerable world‐wide public health burden with incidence as high as one in ten in 12‐month‐old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells.

Objective

Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge‐proven IgE‐mediated food allergy.

Method

We genotyped nine IL13 “tag” single nucleotide polymorphisms (tag SNPs) in 367 challenge‐proven food allergic cases, 199 food‐sensitized tolerant cases and 156 non‐food allergic controls from the HealthNuts study. 12‐month‐old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran‐Mantel‐Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co‐located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non‐food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed.

Results

IL13 rs1295686 was associated with challenge‐proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20‐2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03‐1.82) and further supported by a meta‐analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE.

Conclusions and Clinical Relavance

We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge‐proven food allergy.
A novel TRPA1 variant is associated with carbamazepine‐responsive cramp‐fasciculation syndrome
Authors: Nirenberg M.J. , Chaouni R. , Biller T.M. , Gilbert R.M. , Paisán‐Ruiz C.
Published: April 2017

Cramp‐fasciculation syndrome (CFS) is a rare muscle hyperexcitability syndrome that presents with muscle cramps, fasciculations, and stiffness, as well as pain, fatigue, anxiety, hyperreflexia, and paresthesias. Although familial cases have been reported, a genetic etiology has not yet been identified. We performed whole‐exome sequencing followed by validation and cosegregation analyses on a father‐son pair with CFS. Both subjects manifested other hypersensitivity‐hyperexcitability symptoms, including asthma, gastroesophageal reflux, migraine, restless legs syndrome, tremor, cold hyperalgesia, and cardiac conduction defects. Most symptoms improved with carbamazepine, consistent with an underlying cation channelopathy. We identified a variant in the transient receptor potential ankyrin A1 channel (TRPA1) gene that selectively cosegregated with CFS and the other hypersensitivity‐hyperexcitability symptoms. This variant (c.2755C>T) resulted in a premature stop codon at amino acid 919 (p.Arg919*) in the outer pore of the channel. TRPA1 is a widely distributed, promiscuous plasmalemmal cation channel that is strongly implicated in the pathophysiology of the specific hypersensitivity‐hyperexcitability symptoms observed in these subjects. Thus, we have identified a novel TRPA1 variant that is associated with CFS as part of a generalized hypersensitivity‐hyperexcitability disorder. These findings clarify the diverse functional roles of TRPA1, and underscore the importance of this channel as a potential therapeutic target.
Truncating mutations on myofibrillar myopathies causing genes as prevalent molecular explanations on patients with dilated cardiomyopathy
Authors: Janin A. , N'Guyen K. , Habib G. , Dauphin C. , Chanavat V. , Bouvagnet P. , Eschalier R. , Streichenberger N. , Chevalier P. , Millat G.
Published: April 2017

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. More than 40 genes have been reported to cause DCM. To provide new insights into the pathophysiology of dilated cardiomyopathy, a next‐generation sequencing (NGS) workflow based on a panel of 48 cardiomyopathies‐causing genes was used to analyze a cohort of 222 DCM patients. Truncating variants were detected on 63 unrelated DCM cases (28.4%). Most of them were identified, as expected, on
TTN
(29 DCM probands), but truncating variants were also identified on myofibrillar myopathies causing genes in 17 DCM patients (7.7% of the DCM cohort): 10 variations on
FLNC
and 7 variations on
BAG3
. This study confirms that truncating variants on myofibrillar myopathies causing genes are frequently associated with dilated cardiomyopathies and also suggest that
FLNC
mutations could be considered as a common cause of dilated cardiomyopathy. Molecular approaches that would allow to detect systematically truncating variants in
FLNC
and
BAG3
into genetic testing should significantly increase test sensitivity, thereby allowing earlier diagnosis and therapeutic intervention for many patients with dilated cardiomyopathy.
PDX1‐MODY and dorsal pancreatic agenesis: New phenotype of a rare disease
Authors: Caetano L.A. , Santana L.S. , Costa‐Riquetto A.D. , Lerario A.M. , Nery M. , Nogueira G.F. , Ortega C.D. , Rocha M.S. , Jorge A.A.L. , Teles M.G.
Published: April 2017

Maturity‐Onset Diabetes of the Young (MODY) type 4 or
PDX1
‐MODY is a rare form of monogenic diabetes caused by heterozygous variants in
PDX1
. Pancreatic developmental anomalies related to
PDX1
are reported only in neonatal diabetes cases. Here, we describe dorsal pancreatic agenesis in 2 patients with
PDX1
‐MODY. The proband presented with diabetes since 14 years of age and maintained regular glycemic control with low doses of basal insulin and detectable C‐peptide levels after 38 years with diabetes. A diagnosis of MODY was suspected. Targeted next‐generation sequencing identified a heterozygous variant in
PDX1
: c.188delC/p.Pro63Argfs*60. Computed tomography revealed caudal pancreatic agenesis. Low fecal elastase indicated exocrine insufficiency. His son had impaired glucose tolerance, presented similar pancreatic agenesis, and harbored the same allelic variant. The unusual presentation in this Brazilian family enabled expansion upon a rare disease phenotype, demonstrating the possibility of detecting pancreatic malformation even in cases of
PDX1
‐related diabetes diagnosed after the first year of life. This finding can improve the management of MODY4 patients, leading to precocious investigation of pancreatic dysgenesis and exocrine dysfunction.