bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated Gleason grading of prostate cancer tissue microarrays via deep learning
Authors: Arvaniti Eirini , Fricker Kim S. , Moret Michael , Rupp Niels J. , Hermanns Thomas , Fankhauser Christian , Wey Norbert , Wild Peter J. , Rueschoff Jan H. , Claassen Manfred
Published: March 2018

The Gleason grading system remains the most powerful prognostic predictor for patients with prostate cancer since the 1960’s. Its application requires highly-trained pathologists, is tedious and yet suffers from limited inter-pathologist reproducibility, especially for the intermediate Gleason score 7. Automated annotation procedures constitute a viable solution to remedy these limitations.

In this study, we present a deep learning approach for automated Gleason grading of prostate cancer tissue microarrays with Hematoxylin and Eosin (H&E) staining. Our system was trained using detailed Gleason annotations on a discovery cohort of 641 patients and was then evaluated on an independent test cohort of 245 patients annotated by two pathologists. On the test cohort, the inter-annotator agreements between the model and each pathologist, quantified via Cohen’s quadratic kappa statistic, were 0.75 and 0.71 respectively, comparable with the inter-pathologist agreement (kappa=0.71). Furthermore, the model’s Gleason score assignments achieved pathology expert-level stratification of patients into prognostically distinct groups, on the basis of disease-specific survival data available for the test cohort.

Overall, our study shows promising results regarding the applicability of deep learning-based solutions towards more objective and reproducible prostate cancer grading, especially for cases with heterogeneous Gleason patterns.
Testing the behavioral origins of novelty: did increased aggression lead to scale-eating in pupfishes?
Authors: St. John Michelle E. , McGirr Joseph A. , Martin Christopher H.
Published: March 2018

How novelty evolves is still largely unknown. Environmental changes are often assumed to precede novelty; however, behavioral shifts may also play a role. Here, we examine whether a shift in aggression explains the origin of a novel scale-eating pupfish species (Cyprinodon desquamator) within an adaptive radiation on San Salvador Island, Bahamas. We compared aggression using behavioral and gene expression data across three sympatric species in the San Salvador radiation (generalist, snail-eating specialist, and scale-eating specialist), and additionally measured behavioral aggression in an outgroup generalist from North Carolina. Surprisingly, we found increased behavioral aggression and differential expression of aggression-related genes in both the scale-eating and snail-eating species. Furthermore, male scale-eaters and female snail-eaters showed the highest levels of aggression compared to other groups. Differential gene expression in each specialist during larval development also suggested sex-mediated differences in male-male aggression and maternal care. Ultimately, our data indicate that aggression is not unique to scale-eating specialists. Instead, selection may increase aggression in other contexts such as niche specialization, mate competition, or selection on other ecologically relevant traits, including jaw size. Indeed, some adaptive variants associated with oral jaw size in the San Salvador radiation occur in genetic pathways with pleiotropic effects on aggression.
Expected reward value and reward uncertainty have temporally dissociable effects on memory formation
Authors: Stanek Jessica K. , Dickerson Kathryn C. , Chiew Kimberly S. , Clement Nathaniel J. , Adcock R. Alison
Published: March 2018

Anticipating rewards has been shown to enhance memory formation. While substantial evidence implicates dopamine in this behavioral effect, the precise mechanisms remain ambiguous. Because dopamine nuclei show two distinct physiological signatures of reward prediction, we hypothesized two dissociable effects on memory formation. These two signatures are a phasic dopamine response immediately following a reward cue that encodes its expected value, and a sustained, ramping dopamine response that is greater during high reward uncertainty (Fiorillo, Tobler, & Schultz, 2003). Here, we show in humans that the impact of reward anticipation on memory for an event depends on its timing relative to these physiological signatures. By manipulating reward probability (100%, 50%, or 0%) and the timing of the event to be encoded (just after the reward cue versus just before expected reward outcome), we demonstrated the predicted double dissociation: early during reward anticipation, memory formation was improved by increased expected reward value, whereas late during reward anticipation, memory formation was enhanced by reward uncertainty. Moreover, while the memory benefits of high expected reward in the early interval were consolidation-dependent, the memory benefits of high uncertainty in the later interval were not. These findings support the view that expected reward benefits memory consolidation via phasic dopamine release. The novel finding of a dissociable memory enhancement, temporally consistent with sustained anticipatory dopamine release, points toward new mechanisms of memory modulation by reward now ripe for further investigation.
Evidence of damage evolution during creep of Al–Mg alloy using synchrotron X-ray refraction
Authors: Cabeza Sandra , Müller Bernd R. , Pereyra Rocío , Fernández Ricardo , González-Doncel Gaspar , Bruno Giovanni
Published: March 2018

In order to provide further evidence of damage mechanisms predicted by the recent solid-state transformation creep (SSTC) model, direct observation of damage accumulation during creep of Al–3.85Mg was made using synchrotron X-ray refraction. X-ray refraction techniques detect the internal specific surface (i.e. surface per unit volume) on a length scale comparable to the specimen size, but with microscopic sensitivity. A significant rise in the internal specific surface with increasing creep time was observed, providing evidence for the creation of a fine grain substructure, as predicted by the SSTC model. This substructure was also observed by scanning electron microscopy.
A data-driven method of health monitoring for spacecraft
Authors: Kang Xu , Pi Dechang
Published: March 2018

Purpose

The purpose of this paper is to detect the occurrence of anomaly and fault in a spacecraft, investigate various tendencies of telemetry parameters and evaluate the operation state of the spacecraft to monitor the health of the spacecraft.

Design/methodology/approach

This paper proposes a data-driven method (empirical mode decomposition-sample entropy-principal component analysis [EMD-SE-PCA]) for monitoring the health of the spacecraft, where EMD is used to decompose telemetry data and obtain the trend items, SE is utilised to calculate the sample entropies of trend items and extract the characteristic data and squared prediction error and statistic contribution rate are analysed using PCA to monitor the health of the spacecraft.

Findings

Experimental results indicate that the EMD-SE-PCA method could detect characteristic parameters that appear abnormally before the anomaly or fault occurring, could provide an abnormal early warning time before anomaly or fault appearing and summarise the contribution of each parameter more accurately than other fault detection methods.

Practical implications

The proposed EMD-SE-PCA method has high level of accuracy and efficiency. It can be used in monitoring the health of a spacecraft, detecting the anomaly and fault, avoiding them timely and efficiently. Also, the EMD-SE-PCA method could be further applied for monitoring the health of other equipment (e.g. attitude control and orbit control system) in spacecraft and satellites.

Originality/value

The paper provides a data-driven method EMD-SE-PCA to be applied in the field of practical health monitoring, which could discover the occurrence of anomaly or fault timely and efficiently and is very useful for spacecraft health diagnosis.
Do glamour, self-sexualisation and scopophilia influence celebrity endorsement?
Authors: Carvalho Catarina Peixoto , Azevedo Antonio
Published: March 2018

Purpose

The purpose of this paper is to discuss the influence of glamour, scopophilia and self-sexualisation in luxury celebrity endorsement.

Design/methodology/approach

In step 1, an experimental study was conducted with 100 respondents assessing the response towards manipulated print ad stimuli operationalizing the influence (in general terms) of lay out, endorser’s beauty pattern, body language (cool, smile appeal, sex appeal and disruptive), gazing and landscape. In step 2, respondents evaluated their response towards five perfume print ads retrieved from real advertising campaigns with different brand personalities (DKNY, Moschino, Chanel, Gucci and Boss).

Findings

The ideal copy strategy is: a couple of brunette Caucasian endorsers; “close-up” photo; sexy body language; indirect smiling gaze; and urban landscape. Multiple regression models were built for each ad/brand (personality) in order to predict the willingness to pay for a bottle of perfume.

Research limitations/implications

The paper suggests a holistic theoretical framework describing the influence of celebrity characteristics, advertising copy strategy, social-cultural trends and brand variables in the advertising processing.

Practical implications

Advertising copywriters and brand managers must control the role of glamour and the self-consciousness of women seduction power in branding advertising.

Social implications

Glamour, scopophilia or self-sexualisation are three different concepts which have a lot of sociological implications because they influence the way as the society perceive the role of women as endorsers in advertising, but also in other life dimensions.

Originality/value

This paper fills a gap in the literature, since this paper make an innovative analysis of the influence of these recent post-modernist socio-cultural trends.
Production technologies and low-technology knowledge-intensive venturing
Authors: Karagouni Glykeria
Published: March 2018

Purpose

The purpose of this paper is to explore how low-technology corporate ventures use knowledge from multiple and often trans-sectoral fields to intensively create and deploy innovative production technologies in order to sustain significant competitive advantages.

Design/methodology/approach

The paper primarily draws evidence from an exploratory case study of a low-tech private enterprise operating in the wood processing industry in Greece.

Findings

Low-technology firms appear to invest mainly in process innovation and therefore production technologies, in order to secure a position within mature markets. Within the notion of knowledge-intensive entrepreneurship (KIE), a creative bricolage of knowledge based on research work and industrial practice results in innovative products and processes covering technologies from a wide range, including high-tech industries. The case indicates that low-tech companies may be something more than just “borrowers” of technology.

Research limitations/implications

The limitations regard the single case study research design and the focus on the wood industry in Greece. Future research may pursue more case studies in different traditional sectors and national contexts.

Practical implications

Entrepreneurs and managers of low-technology firms should focus on technological innovation and more specifically on co-creation of novel production technologies in order to sustain strong competitive advantages and enhance performances.

Originality/value

The analysis challenges the established opinion of common entrepreneurial processes in low-tech sectors. It adds to the ongoing discussion of low-tech, KIE and it contributes to the literature of industrial dynamics since there are only a handful of studies that probe the role of production technologies within a low-tech but knowledge-intensive context.
Developing teachers’ mathematical-task knowledge and practice through lesson study
Authors: Barber Krystal
Published: March 2018

Purpose

The purpose of this paper is to examine how lesson study can lead to teacher learning and improvement of instruction by developing teachers’ mathematical-task knowledge and by supporting teachers’ selection, modification, and implementation of mathematical tasks. Mathematical-task knowledge includes knowledge needed to use tasks that require a high level of thinking and reasoning.

Design/methodology/approach

A qualitative case study design was used to explore the learning and instruction of three teachers as they went through the process of lesson study, developed knowledge around mathematics tasks, and made changes to their instruction. Methods included direct observation of lessons, semi-structured interviews, and participant observation.

Findings

This lesson study project supported teachers in developing mathematical-task knowledge and in making change to instructional practice. The teachers discussed in this paper added to their understanding of mathematical tasks and changed how they implemented tasks after lesson study. The teachers began to challenge students to go beyond memorizing or executing procedures to deepen the students’ understanding of mathematical concepts. Teachers developed key insights and understandings of mathematical tasks, triggering shifts in their thinking, and changes to instruction. Collaboration and reflection altered the selection, modification, and implementation of mathematical tasks.

Research limitations/implications

This study reveals the connections between features of lesson study and the pathways that lead to learning and improvements to instruction. Limitations included the demands of the school district’s pacing guide and curriculum, and a limited number of interviews and observations were conducted after lesson study.

Originality/value

There are many different ways lesson study has been implemented in the USA, yet the effectiveness of many lesson study projects is still unclear. This study reveals more about the lesson study process, what features are important, and how these features lead to development of knowledge and practice. This study examines how teachers within the same lesson study group added to their knowledge and practice and how different features of lesson study prompt them to make changes.
Learning from safeguarding adult reviews on self-neglect: addressing the challenge of change
Authors: Preston-Shoot Michael
Published: March 2018

Purpose

The purpose of this paper is to update the core data set of self-neglect safeguarding adult reviews (SARs) and accompanying thematic analysis, and to address the challenge of change, exploring the necessary components beyond an action plan to ensure that findings and recommendations are embedded in policy and practice.

Design/methodology/approach

Further published reviews are added to the core data set from the websites of Safeguarding Adults Boards (SABs). Thematic analysis is updated using the four domains employed previously. The repetitive nature of the findings prompts questions about how to embed policy and practice change, to ensure impactful use of learning from SARs. A framework for taking forward an action plan derived from an SAR findings and recommendations is presented.

Findings

Familiar, even repetitive findings emerge once again from the thematic analysis. This level of analysis enables an understanding of both local geography and the national legal, policy and financial climate within which it sits. Such learning is valuable in itself, contributing to the evidence base of what good practice with adults who self-neglect looks like. However, to avoid the accusation that lessons are not learned, something more than a straightforward action plan to implement the recommendations is necessary. A framework is conceptualised for a strategic and longer-term approach to embedding policy and practice change.

Research limitations/implications

There is still no national database of reviews commissioned by SABs so the data set reported here might be incomplete. The Care Act 2014 does not require publication of reports but only a summary of findings and recommendations in SAB annual reports. This makes learning for service improvement challenging. Reading the reviews reported here enables conclusions to be reached about issues to address locally and nationally to transform adult safeguarding policy and practice.

Practical implications

Answering the question “how to create sustainable change” is a significant challenge for SARs. A framework is presented here, drawn from research on change management and learning from the review process itself. The critique of serious case reviews challenges those now engaged in SARs to reflect on how transformational change can be achieved to improve the quality of adult safeguarding policy and practice.

Originality/value

The paper extends the thematic analysis of available reviews that focus on work with adults who self-neglect, further building on the evidence base for practice. The paper also contributes new perspectives to the process of following up SARs by using the findings and recommendations systematically within a framework designed to embed change in policy and practice.
Through a glass darkly: exploring commissioning and contract monitoring and its role in detecting abuse in care and nursing homes for older people
Authors: Moore Steve
Published: March 2018

Purpose

The purpose of this paper is to present findings from face-to-face interviews undertaken with 16 care and nursing home managers employed in homes situated in two English local authorities. The research sought to explore managers’ perceptions of the role of contract monitoring in the prevention of abuse.

Design/methodology/approach

Semi-structured interviews were undertaken with 16 care and nursing home managers.

Findings

Though personnel employed by the local authority who conducted contract monitoring were generally thought of positively by care home managers on a personal level, their effectiveness was perceived to be limited as a result of their lack of experience and knowledge of providing care, and the methods that they were required to use.

Research limitations/implications

Though the research draws upon the experiences of only 16 care and nursing home managers in two local authorities, data suggest that current contract monitoring activity is of limited utility in determining the true nature of care and the presence of abuse.

Originality/value

Unusually, the paper explores care and nursing home managers’ perceptions of contract monitoring processes in terms of how they perceive their effectiveness in preventing abuse.
Institutional drivers of born-public ventures
Authors: DeGhetto Kaitlyn , Sutton Trey , Zorn Michelle L.
Published: March 2018

Purpose

The purpose of this paper is to identify and theoretically delineate the government-based institutional drivers of “born-public ventures” – ventures that seek to fulfill government contracts or sell goods and services to government agencies.

Design/methodology/approach

The authors develop theory that explains how the government influences the pursuit of public sector opportunities, thereby influencing where new ventures expend their finite effort. Specifically, the authors use institutional theory to delineate the regulatory, cognitive, and normative drivers of born-public ventures. In doing so, the authors highlight both the government’s regulative and non-regulative institutional influences. Finally, the authors present a research agenda to encourage further understanding of this important phenomenon.

Findings

The authors find that the government can affect the allocation of finite entrepreneurial effort toward or away from public sector opportunities by using regulative, normative, and cognitive institutional forces. This influence is important because entrepreneurship targeted at the public sector likely has broad implications for the economy and society as a whole.

Originality/value

Despite recent attention to questions about entrepreneurial allocation, scholars have largely overlooked the importance of why some new ventures choose to allocate their effort toward public sector opportunities. Given the growing number of public sector opportunities and the potential economic and societal implications associated with pursuing these opportunities, research is needed to understand this allocative choice. By introducing the phenomenon of born-public ventures and outlining important research questions, this theoretical paper provides the foundation for further work on this topic.
Evaluating relief center designs for disaster relief distribution
Authors: Ozen Merve , Krishnamurthy Ananth
Published: March 2018

Purpose

Relief item distribution to victims is a key activity during disaster response. Currently many humanitarian organizations follow simple guidelines based on experience to assess need and distribute relief supplies. However, the interviews with practitioners suggest a problem in efficiency in relief distribution efforts. The purpose of this paper is to develop a model and solution methodology that can estimate relief center (RC) performance, measured by waiting time for victims and throughput, for any RC design and analyze the impact of key design decisions on these performance measures.

Design/methodology/approach

Interviews with practitioners and current practice guidelines are used to understand relief distribution and a queuing network model is used to represent the relief distribution. Finally, the model is applied to data from the 2015 Nepal earthquake.

Findings

The findings identify that dissipating congestion created by crowds, varying item assignment decisions to points of distribution, limiting the physical RC capacity to control congestion and using triage queue to balance distribution times, are effective strategies that can improve RC performance.

Research limitations/implications

This research bases the RC designs on Federal Emergency Management Agency guidelines and assumes a certain area and volunteer availability.

Originality/value

This paper contributes to humanitarian logistics by discussing useful insights that can impact how relief agencies set up and operate RCs. It also contributes to the queuing literature by deriving analytic solutions for the steady state probabilities of finite capacity, state dependent queues with blocking.
Peer-to-peer accommodation and sustainability in Mountain areas
Authors: Dornier Raphaël , Selmi Noureddine
Published: March 2018

Purpose

This paper aims to formulate assumptions on home sharing users’ sensitivity toward sustainability in mountain areas and define the sustainability indicators that may be used to search for home-based accommodation in mountain areas.

Design/methodology/approach

The paper is based on a literature review of key terms: mountain tourism, peer-to-peer accommodation and sustainability indicators.

Findings

Tourists in mountain areas are more likely to be sensitive toward sustainability than in urban areas, so they are likely to expect home sharing websites to provide sustainability criteria for selecting their accommodation.

Practical implications

Home sharing platforms should offer to mountain tourists the possibility to search for and assess home-based accommodation using sustainability criteria.

Originality/value

Most studies on peer-to-peer accommodation were designed in urban areas. The authors state that in mountain areas, tourists are more sensitive toward sustainability and would therefore be more inclined to consider sustainability in their search for a home-based accommodation.
We All Make Mistakes: A ‘Duty of Virtue’ Theory of Restitutionary Liability for Mistaken Payments
Authors: Penner J. E.
Published: March 2018

In contrast to the moral foundations of contract, tort, and the law of property, which are generally regarded as elements of Kantian ‘right’, the liability to return the value of mistaken payments is, it is argued, an example of the law's enforcing a duty of virtue, the legalisation of the duty of beneficence in a way similar (though not identical) to how the law might instantiate a duty of easy rescue. Accordingly, one of Birks's most cherished theses – that the law of unjust enrichment represents a distinctive element of private law – can be made out: it is distinctive in having an entirely different normative source: in virtue, not in right. But this result comes at a cost: (1) a legal system could function more or less justly without such a liability; (2) Birks's thesis that liability for mistaken payment is the archetype or paradigmatic case of liability for unjust enrichment would have to be abandoned; and (3) we would have to recognise that the ground of this liability is policy‐motivated.
Ideological Neutrality in the Workplace
Authors: Adams Zoe , Adenitire John Olusegun
Published: March 2018

This note assesses the decisions of the Court of Justice of the European Union in Achbita v G4S Secure Solutions NV and Bougnaoui v Micropole SA, the first cases dealing with religious discrimination under the Equal Treatment Directive 2000/43. Both cases concerned Muslim women wishing to express their religious beliefs by wearing an Islamic headscarf while working in a private undertaking. The Court held that the employees’ dismissal could not be justified by reference to clients’ prejudices against the headscarf. However, dismissal could be justified if pursued on the basis of a corporate policy of ideological neutrality which prohibited all visible religious, political and philosophical symbols. This note criticises the latter part of the Court's decision for, inter alia, placing too much weight on an employer's freedom to run its business in spite of the grave effects this has on employees’ fundamental right to manifest their beliefs at work.
Do we need warm leaders? Exploratory study of the role of voter evaluations of leaders’ traits on turnout in seven European countries
Authors: FERREIRA DA SILVA FREDERICO , COSTA PATRÍCIO
Published: March 2018

Previous research on leader effects has focused exclusively on the impact of voters’ evaluations of leaders on vote choice, disregarding possible effects on the prior step of deciding whether or not to turn out to vote. In line with the personalisation of politics thesis, leaders have a higher impact among dealigned voters. Previous studies have demonstrated that leader effects are stronger among voters who voice their dealignment – namely party switchers. However, the potential impact of leaders among those who exited (i.e., who have abstained) is still unstudied. Could leaders have a mobilisation effect and therefore trigger turnout decisions? What characteristics of party leaders are more relevant in this regard? This article is the first comparative study to examine how the evaluation of party leaders’ traits influences voter turnout in general elections. The work incorporates data from election studies across seven countries with different social contexts (Portugal, Spain, Ireland, Germany, United Kingdom, Italy and Hungary). Characteristics of leaders were grouped into two dimensions – competence and warmth – in accordance with the stereotype content model and relevant studies on leaders’ traits evaluation. Multiple binary logistic regression models were performed to analyse the predictive power of competence and warmth on turnout, controlling for sociodemographic, political ideology variables and voters’ past political behaviour. Results reinforce the personalisation of politics theory, showing the utmost relevance of warmth personality traits of leaders in voter turnout decisions. Competence personality traits were found to be relevant only in some situations. Interaction effects were also demonstrated between warmth evaluations and identifying with a right‐wing party as well as past political behaviour with both warmth and competence.
The role of management and trade union leadership on dual commitment: The mediating effect of the workplace relations climate
Authors: Fortin‐Bergeron Chloe , Doucet Olivier , Hennebert Marc‐Antonin
Published: March 2018

This article examines the effect of transformational and laisser‐faire leadership on the part of local union leaders and immediate supervisors on the dual commitment of unionised workers. Building on the social information processing perspective, it is suggested that these leadership styles are linked to commitment through the workplace relations climate (WRC). Based on a sample of 834 unionised workers, our results suggest that WRC represents an important mechanism explaining the effect of the immediate supervisor's leadership in unionised settings. Results also show that transformational leadership on the part of union representatives is positively linked to union and organisational commitment. This article contributes to the WRC and dual commitment literatures by going beyond structural and institutional explanations and considering relational and actor‐related variables, such as leadership styles.
The Who, When, and Where of Executive Nominations: Integrating Agency Independence and Appointee Ideology
Authors: Hollibaugh Gary E. , Rothenberg Lawrence S.
Published: March 2018

In recent years, scholars have expended considerable efforts to understand the executive appointment process and the forces influencing the choices made by the president and the Senate. However, some factors integral to theoretical models have not been well integrated empirically, and other relevant factors have not been incorporated much at all. Here, we focus on one determinant corresponding to the former critique—nominee ideology—and another corresponding to the latter—the independence of decision makers in the targeted agencies. We examine a series of theoretically driven hypotheses regarding the effects of both ideology and independence on who gets nominated and if and when nominees are eventually confirmed. Results show nominee ideology and decision maker independence matter a great deal and factor into presidential strategic choices and senatorial responses in ways according to expectations. Our findings have important ramifications for understanding appointments empirically and for future theoretical development.
Prominent Role Models: High‐Profile Female Politicians and the Emergence of Women as Candidates for Public Office
Authors: Ladam Christina , Harden Jeffrey J. , Windett Jason H.
Published: March 2018

Can prominent female politicians inspire other women to enter politics? A woman occupying a high‐profile office directly impacts women's substantive representation through her policy actions. Here, we consider whether these female leaders also facilitate a mobilization effect by motivating other women to run for office. We posit that prominent women in politics serve as role models for other women interested in political careers, causing an increase in female candidates. We test this theory with data from the American states, which exhibit considerable variation in the sex of state legislative candidates and the high‐profile offices of governor and U.S. senator. Using a weighting method and data spanning 1978–2012, we demonstrate that high‐profile women exert substantively large positive effects on female candidates. We conclude that women in major offices are crucial for women's representation. Beyond their direct policy impact, they amplify women's political voice by motivating more women to enter politics.
Development of a selective androgen receptor modulator for transdermal use in hypogonadal patients
Authors: Krishnan V. , Patel N. J. , Mackrell J. G. , Sweetana S. A. , Bullock H. , Ma Y. L. , Waterhouse T. H. , Yaden B. C. , Henck J. , Zeng Q. Q. , Gavardinas K. , Jadhav P. , Saeed A. , Garcia‐Losada P. , Robins D. A. , Benson C. T.
Published: March 2018

We have identified a non‐steroidal selective androgen receptor modulator (SARM), termed LY305, that is bioavailable through a transdermal route of administration while highly cleared via hepatic metabolism to limit parent compound exposure in the liver. Selection of this compound and its transdermal formulation was based on the optimization of skin absorption properties using both in vitro and in vivo skin models that supported PBPK modeling for human PK predictions. This molecule is an agonist in perineal muscle while being a weak partial agonist in the androgenic tissues such as prostate. When LY305 was tested in animal models of skeletal atrophy it restored the skeletal muscle mass through accelerated repair. In a bone fracture model, LY305 remained osteoprotective in the regenerating tissue and void of deleterious effects. Finally, in a small cohort of healthy volunteers, we assessed the safety and tolerability of LY305 when administered transdermally. LY305 showed a dose‐dependent increase in serum exposure and was well tolerated with minimal adverse effects. Notably, there were no statistically significant changes to hematocrit or HDL after 4‐week treatment period. Collectively, LY305 represents a first of its kind de novo development of a non‐steroidal transdermal SARM with unique properties which could find clinical utility in hypogonadal men.
Platelet‐leucocyte aggregation is augmented in cirrhosis and further increased by platelet transfusion
Authors: Støy S. , Patel V. C. , Sturgeon J. P. , Manakkat Vijay G. K. , Lisman T. , Bernal W. , Shawcross D. L.
Published: March 2018

Background

Thrombocytopenia and circulating dysfunctional immune cells are commonly observed in patients with cirrhosis. Platelets may form complexes with neutrophils, monocytes and T cells modulating their function. We recently reported increased frequencies of platelet‐complexed neutrophils in cirrhosis with evidence of neutrophil activation upon contact with healthy platelets in vitro. Whether this occurs in vivo following platelet transfusion and contributes to systemic inflammation and endothelial activation is unknown.

Aims

To characterise platelet‐leucocyte aggregation in cirrhosis and to determine whether elective platelet transfusion results in perturbations associated with changes in markers of haemostasis, inflammation or endothelial activation.

Methods

We collected blood from cirrhotics (n = 19) before and following elective platelet transfusion. We measured platelet‐leucocyte aggregation, activation and function, and markers of platelet activation, systemic inflammation and endothelial activation by flow cytometry. Haemostasis was assessed by thromboelastometry and plasma haemostatic proteins.

Results

We observed a 2.5‐fold increase in platelet‐complexed neutrophils in patients with cirrhosis compared with healthy subjects and twofold more platelets attached per monocyte and T cell. All platelet‐complexed leucocytes expressed higher levels of activation markers and platelet‐complexed neutrophils had higher resting oxidative burst and phagocytic capacity than their nonplatelet‐complexed counterparts (P < 0.001); most pronounced in patients with cirrhosis. Paradoxically, platelet‐complexed leucocyte frequency decreased with increasing MELD score. Platelet transfusion increased soluble CD40 ligand (platelet activation marker), the frequency of platelet‐complexed monocytes (P < 0.05) and improved haemostatic status.

Conclusion

Cirrhotic patients have activated circulating platelet‐complexed leucocytes with increased platelet‐monocyte aggregation following elective platelet transfusion. Elective platelet transfusion might therefore exacerbate immune dysfunction in cirrhosis.
Validation of the oesophageal hypervigilance and anxiety scale for chronic oesophageal disease
Authors: Taft T. H. , Triggs J. R. , Carlson D. A. , Guadagnoli L. , Tomasino K. N. , Keefer L. , Pandolfino J. E.
Published: March 2018

Background

Oesophageal hypervigilance and anxiety can drive symptom experience in chronic oesophageal conditions, including gastro‐oesophageal reflux disease, achalasia and functional oesophageal disorders. To date, no validated self‐report measure exists to evaluate oesophageal hypervigilance and anxiety.

Aims

This study aims to develop a brief and reliable questionnaire assessing these constructs, the oesophageal hypervigilance and anxiety scale (EHAS).

Methods

Questions for the EHAS were drawn from 4 existing validated measures that assessed hypervigilance and anxiety adapted for the oesophagus. Patients who previously underwent high‐resolution manometry testing at a university‐based oesophageal motility clinic were retrospectively identified. Patients were included in the analysis if they completed the EHAS as well as questionnaires assessing symptom severity and health‐related quality of life at the time of the high‐resolution manometry.

Results

Nine hundred and eighty‐two patients aged 18‐85 completed the study. The EHAS demonstrates excellent internal consistency (α = 0.93) and split‐half reliability (Guttman = 0.87). Inter‐item correlations indicated multicollinearity was not achieved; thus, no items were removed from the original 15‐item scale. Principal components factor analysis revealed two subscales measuring symptom‐specific anxiety and symptom‐specific hypervigilance. Construct validity for total and subscale scores was supported by positive correlations with symptom severity and negative correlations with health‐related quality of life.

Conclusions

The EHAS is a 15‐item scale assessing oesophageal hypervigilance and symptom‐specfic anxiety. The EHAS could be useful in evaluating the role of these constructs in several oesophageal conditions in which hypersensitivity, hypervigilance and anxiety may contribute to symptoms and impact treatment outcomes.
ASEAN Forum on Migrant Labour: A space for civil society in migration governance at the regional level?
Authors: Rother Stefan
Published: March 2018

The aim of this article is to discuss and substantiate new spaces for the political participation of migrant civil society at the regional level in Southeast Asia through the lens of the Association of Southeast Asian Nations (ASEAN) Forum on Migrant Labour (AFML). The AFML process is shaped by the International Labour Organisation and mirrors its tripartite format, essentially bringing together governments, employers’ and workers’ organisations. Crucially, migrant support and self‐organisations also have access, even if somewhat restricted, to regularly held deliberations. In light of the ASEAN consensus on migration that was agreed upon at the end of 2017, the article situates the AFML within the ongoing process of migration governance in the region and focusses especially on the role of migrant civil society as an important stakeholder. Based on the specific experience of civil society organisations (CSOs) from Malaysia, the article discusses which spaces the forum provides for civil society actors and how the latter use them for their advocacy. The major argument of the article is that the development of migration policies at the regional level can benefit from the inclusion of migrant civil society in the process. The governance of migrants could thus be complemented by governance for and by migrants.
Advancing the Analysis of Past Human/Plant Relationships: Methodological Improvements of Artefact Pollen Washes
Authors: Miras Y. , Ejarque A. , Barbier‐Pain D. , Corbineau R. , Ledger P. M. , Riera Mora S. , Garreau A. , Voldoire O. , Allain E. , Mangado Llach J. , Sánchez De La Torre M. , Martínez‐Grau H. , Bergadá M. M. , Smith S. J.
Published: March 2018

The ‘pollen washes’ technique, based on the analysis of the pollen embedded in the porous surface of archaeological artefacts, is developed for investigating past plant usage and consumption and to characterize the functionality of artefacts related to plant processing, gathering and storage. The research presented results in relevant methodological improvements of this technique, which has never previously been applied on materials from European contexts. The improvements allow: (1) faster analysis of a broad series of artefacts or those with large use‐surface areas likely to retain more pollen; and (2) a more thorough, deeper and precise cleaning method, allowing the study of smoother artefacts. Finally, the recovery of Trifolium‐group pollen from a macro‐lithic tool from Xicotó rock shelter (Montsec ranges, Spain) demonstrates that the pollen washes technique can reveal new insights into both the use and consumption of wild and domestic plants by prehistoric societies, and the functionality of archaeological objects whose interpretation is still problematic.
Cytochrome P450 Induction and Xeno‐Sensing Receptors Pregnane X Receptor, Constitutive Androstane Receptor, Aryl Hydrocarbon Receptor and Peroxisome Proliferator‐Activated Receptor α at the Crossroads of Toxicokinetics and Toxicodynamics
Authors: Hakkola Jukka , Bernasconi Camilla , Coecke Sandra , Richert Lysiane , Andersson Tommy B. , Pelkonen Olavi
Published: March 2018

Pregnane X receptor (PXR), constitutive androstane receptor (CAR), aryl hydrocarbon receptor (AHR) and peroxisome proliferator‐activated receptor α (PPARα) are ligand‐activated transcription factors that regulate expression of many xenobiotic‐metabolizing enzymes including several cytochrome P450 (CYP) enzymes. Many xenobiotics induce CYP enzymes through these intracellular receptors and consequently affect toxicokinetics and possible metabolic activation of the receptor ligands and other xenobiotics utilizing similar metabolic pathways. However, it is now apparent that the xenobiotic receptors regulate also many endogenous functions and signalling pathways, and xenobiotic exposure thus may dysregulate an array of fundamental cell functions. This MiniReview surveys and discusses the multifaceted roles of xenobiotic receptors, for which CYP induction may serve as the first alert and possibly a biomarker for exposure to xenobiotics. With the current emergence of the adverse outcome pathway (AOP) concept, these receptors are being and will be assigned as molecular initiating events or key events in numerous discrete toxicity pathways.
Neither fish nor fowl: A perceived mismatch in norms and values between oneself, other students, and people back home undermines adaptation to university
Authors: de Vreeze Jort , Matschke Christina , Cress Ulrike
Published: March 2018

Students from low social‐class background often struggle to adapt to university. Previous research shows that perceived incompatibility between social‐class background identity and student identity is one reason, but little is known about the underlying causes of identity incompatibility. In three studies, we expected and found that students with low subjective social‐class background perceived their values differently from other students, but also differently from people back home, and both increased identity incompatibility. Identity incompatibility negatively affected the student identity. Additionally, the current research also identifies specific patterns of norm and value differences that are prone to perceived identity incompatibility. The findings demonstrate that perceived differences in values from both groups are important mechanisms for identity incompatibility induced by the transition to university that may affect student identities and potentially their university trajectories.
Dysregulation of miRNA and its potential therapeutic application in schizophrenia
Authors: Cao Ting , Zhen Xue‐Chu
Published: March 2018

Although it is generally believed that genetic and developmental factors play critical roles in pathogenesis of schizophrenia, however, the precise etiological mechanism of schizophrenia remains largely unknown. Over past decades, miRNAs have emerged as an essential post‐transcriptional regulator in gene expression regulation. The importance of miRNA in brain development and neuroplasticity has been well‐established. Abnormal expression and dysfunction of miRNAs are known to involve in the pathophysiology of many neuropsychiatric diseases including schizophrenia. In this review, we summarized the recent findings in the schizophrenia‐associated dysregulation of miRNA and functional roles in the development and pathogenesis of schizophrenia. We also discussed the potential therapeutic implications of miRNA regulation in the illness.
Initial evaluation of the effects of an environmental‐focused problem‐solving intervention for transition‐age young people with developmental disabilities: Project TEAM
Authors: Kramer Jessica M , Helfrich Christine , Levin Melissa , Hwang I‐Ting , Samuel Preethy S , Carrellas Ann , Schwartz Ariel E , Goeva Aleksandrina , Kolaczyk Eric D
Published: March 2018

Aim

Project TEAM (Teens making Environment and Activity Modifications) teaches transition‐age young people with developmental disabilities, including those with co‐occurring intellectual or cognitive disabilities, to identify and resolve environmental barriers to participation. We examined its effects on young people's attainment of participation goals, knowledge, problem‐solving, self‐determination, and self‐efficacy.

Method

We used a quasi‐experimental, repeated measures design (initial, outcome, 6‐week follow‐up) with two groups: (1) Project TEAM (28 males, 19 females; mean age 17y 6mo); and (2) goal‐setting comparison (21 males, 14 females; mean age 17y 6mo). A matched convenience sample was recruited in two US states. Attainment of participation goals and goal attainment scaling (GAS) T scores were compared at outcome. Differences between groups for all other outcomes were analyzed using linear mixed effects models.

Results

At outcome, Project TEAM participants demonstrated greater knowledge (estimated mean difference: 1.82; confidence interval [CI]: 0.90, 2.74) and ability to apply knowledge during participation (GAS: t[75]=4.21; CI: 5.21, 14.57) compared to goal‐setting. While both groups achieved significant improvements in knowledge, problem‐solving, and self‐determination, increases in parent reported self‐determination remained at 6‐week follow‐up only for Project TEAM (estimated mean difference: 4.65; CI: 1.32, 7.98). Significantly more Project TEAM participants attained their participation goals by follow‐up (Project TEAM=97.6%, goal‐setting=77.1%, p=0.009).

Interpretation

Both approaches support attainment of participation goals. Although inconclusive, Project TEAM may uniquely support young people with developmental disabilities to act in a self‐determined manner and apply an environmental problem‐solving approach over time.

What this paper adds

Individualized goal‐setting, alone or during Project TEAM (Teens making Environment and Activity Modifications) appears to support attainment of participation goals.

Project TEAM appears to support young people with developmental disabilities to apply an environmental problem‐solving approach to participation barriers.

Parents of young people with developmental disabilities report sustained changes in self‐determination 6 weeks after Project TEAM.
The politics of special purpose trust funds
Authors: Eichenauer Vera Z. , Hug Simon
Published: March 2018

Over the last decades, bilateral donors of foreign aid have increased their use of special purpose trust funds to provide earmarked aid to multilateral organizations. This paper investigates the incentives and consequences underlying this recent shift toward country‐ or theme‐specific funding and away from bilateral and multilateral aid. We propose a game‐theoretic model with multiple principals and a multilateral agent to study how the interaction between donor preferences, voter concerns in the donor country, the voting rules at the multilateral organization, and the presence of special purpose trust funds influences aid allocation. We show that multilateral organizations with majority rules are more likely to receive discretion and thus voluntary core contributions than those with unanimity requirements and that the possibility of earmarking multilateral aid decreases donors’ contributions to the multilateral's discretionary core budget and the amount of bilateral aid. In contrast to much of the literature dealing with issues of delegation and bi‐ and multilateral aid, our model suggests non‐monotonic effects of preference heterogeneity on the choice of aid channel for some parameter combinations when contributions to special purpose trust funds are an option.