bluuebunny/crossref_metadata_2025 huggingface dataset:
Punctuated evolution shaped modern vertebrate diversity
Authors: Landis Michael J. , Schraiber Joshua G.
Published: June 2017

The relative importance of different modes of evolution in shaping phenotypic diversity remains a hotly debated question. Fossil data suggest that stasis may be a common mode of evolution, while modern data suggest very fast rates of evolution. One way to reconcile these observations is to imagine that evolution is punctuated, rather than gradual, on geological time scales. To test this hypothesis, we developed a novel maximum likelihood framework for fitting Lévy processes to comparative morphological data. This class of stochastic processes includes both a gradual and punctuated component. We found that a plurality of modern vertebrate clades examined are best fit by punctuated processes over models of gradual change, gradual stasis, and adaptive radiation. When we compare our results to theoretical expectations of the rate and speed of regime shifts for models that detail fitness landscape dynamics, we find that our quantitative results are broadly compatible with both microevolutionary models and with observations from the fossil record.
Genome Architecture Leads a Bifurcation in Cell Identity
Authors: Liu Sijia , Chen Haiming , Ronquist Scott , Seaman Laura , Ceglia Nicholas , Muir Lindsey A. , Meixner Walter , Chen Pin-Yu , Higgins Gerald , Baldi Pierre , Smale Steve , Hero Alfred , Rajapakse Indika
Published: June 2017

Genome architecture is important in transcriptional regulation and study of its features is a critical part of fully understanding cell identity. Altering cell identity is possible through overexpression of transcription factors (TFs); for example, fibroblasts can be reprogrammed into muscle cells by introducing MYOD1. How TFs dynamically orchestrate genome architecture and transcription as a cell adopts a new identity during reprogramming is not well understood. Here we show that MYOD1-mediated reprogramming of human fibroblasts into the myogenic lineage undergoes a critical transition, which we refer to as a bifurcation point, where cell identity definitively changes. By integrating knowledge of genome-wide dynamical architecture and transcription, we found significant chromatin reorganization prior to transcriptional changes that marked activation of the myogenic program. We also found that the local architectural and transcriptional dynamics of endogenous MYOD1 and MYOG reflected the global genomic bifurcation event. These TFs additionally participate in entrainment of biological rhythms. Understanding the system-level genome dynamics underlying a cell fate decision is a step toward devising more sophisticated reprogramming strategies that could be used in cell therapies.
Distinct roles of the polarity factors Boi1 and Boi2 in the control of exocytosis and abscission in budding yeast
Authors: Masgrau Aina , Battola Andrea , Sanmartin Trinidad , Pryszcz Leszek P. , Gabaldón Toni , Mendoza Manuel
Published: June 2017

Boi1 and Boi2 (Boi1/2) are budding yeast plasma membrane proteins that function in polarized growth, and in cytokinesis inhibition in response to chromosome bridges via the NoCut abscission checkpoint. How Boi1/2 act in these two distinct processes is not understood. We demonstrate that Boi1/2 are required for a late step in the fusion of secretory vesicles with the plasma membrane of the growing bud. Cells lacking Boi1/2 accumulate secretory vesicles and are defective in bud growth. In contrast, Boi2 is specifically required for abscission inhibition in cells with chromatin bridges. The SH3 domain of Boi2, which is dispensable for bud growth and targets Boi2 to the site of abscission, is essential for abscission inhibition. Gain of function of the exocyst, a conserved protein complex involved in tethering of exocytic vesicles to the plasma membrane, rescued secretion and bud growth defects in boi mutant cells, and abrogated NoCut checkpoint function. Thus, Boi2 functions redundantly with Boi1 to promote the fusion of secretory vesicles with the plasma membrane at sites of polarized growth, and acts as an abscission inhibitor during cytokinesis in response to chromatin bridges.
The effect of the CEO’s characteristics on EM: evidence from Jordan
Authors: Alqatamin Rateb Mohammmad , Aribi Zakaria Ali , Arun Thankom
Published: June 2017

Purpose

This study aims to examine the effect of CEO’s personal characteristics on earnings management (EM) practices.

Design/methodology/approach

The authors use panel data for 201 non-financial companies listed on the Amman Stock Exchange (ASE) for the period 2008-2013. The authors use random effect models to test the hypothesis of this study and extent the analysis to family versus non-family.

Findings

The study finds a positive relation between CEO’s overconfidence and EM practices in Jordan. Moreover, the findings reveal that managers in family companies are more likely to engage in EM practices than non-family companies. The findings shed more light on the intricate relationship between CEO’s characteristics, the decision-making process and financial reporting.

Practical implications

Results of this study could be beneficial for a number of users of financial information such as investors, auditors, regulators, lenders, as well other players in the capital market to make right decisions.

Originality/value

A literature review finds that much less studies have investigated the relationship between EM practices and personal CEO characteristics (gender and overconfidence) in developing countries such as Jordan. Furthermore, no study yet has examined the influence of CEO age on EM practices. The authors extend previous literature by providing empirical evidence about effect of some personal CEO’s characteristics on EM practices.
Size, trading volume, and the profitability of technical trading
Authors: Chang Yung-Ho , Jong Chia-Ching , Wang Sin-Chong
Published: June 2017

Purpose

The purpose of this paper is to evaluate the profitability of technical trading relative to buy-and-hold (BH) strategy at firm level, controlling for firm size and trading volume.

Design/methodology/approach

This paper applies variable-length moving averages (VMAs) thoroughly to each and every stock listed on Taiwan Stock Exchange (TWSE) and computes the excess returns of technical trading relative to BH strategy. The samples are further grouped by firm size and trading volume. Furthermore, possible data snooping bias is investigated by employing Hansen’s (2005) Superior Predictive Ability tests.

Findings

The result shows that VMAs outperform the BH strategy. The profitability of VMAs, remarkably, is positively associated with size and trading volume. After correcting for data snooping bias, VMAs with longer moving averages outperform VMAs with shorter moving averages. The evidence suggests that size and volume information is accountable for trend projection.

Originality/value

Unlike past studies simply applying technical trading rules to market indices, portfolios, or selected stocks, this paper evaluates the profitability of technical trading by applying VMAs comprehensively to each and every individual stock listed on TWSE controlling for the effect of firm size and trading volume, providing more practical insights for trading individual stocks.
What motivates social entrepreneurs to start social ventures?
Authors: Ghalwash Seham , Tolba Ahmed , Ismail Ayman
Published: June 2017

Purpose

This study aims to explore the characteristics and backgrounds of social entrepreneurs, particularly in relation to what motivates them to start new social ventures, through an empirical examination of the phenomenon of social entrepreneurship in the specific context of Egypt.

Design/methodology/approach

The study adopts a qualitative methodological approach based on a triangulation of data sources, including extensive interviews from five social entrepreneurs, interviews with senior executives in their organisations and industry experts, as well as secondary data.

Findings

The paper proposes a model that integrates common characteristics and motivations among individuals who start social ventures. Findings confirm the characteristics of social entrepreneurs as compassionate risk-takers with entrepreneurial mindsets who seek to address social issues in innovative ways. They also have the perseverance to face the inefficient institutional frameworks prevalent in developing economies. Social entrepreneurs are motivated by social problems and challenges, inspiration, and previous personal experiences, as well as their social networks.

Research limitations/implications

There are limitations pertaining to the limited sample size and single country focus.

Practical implications

This research offers useful and practical insights for current and future social entrepreneurs, particularly in developing economies. Moreover, the study contributes to expanding future research on social entrepreneurship in similar contexts.

Originality/value

This study makes several contributions to the literature on social entrepreneurship. First, by presenting an integrated model for the characteristics/traits and motivations of social entrepreneur. Second, it provides deeper understanding of social entrepreneurship in emerging economies. Third, it highlights the importance of personal inspiration and informal social networks as two sources of motivation for social entrepreneurs, in emerging countries.
The role of livestock intensification and landscape structure in maintaining tropical biodiversity
Authors: Alvarado Fredy , Escobar Federico , Williams David R. , Arroyo‐Rodríguez Víctor , Escobar‐Hernández Fernando
Published: June 2017

As tropical cattle ranching continues to expand, successful conservation will require an improved understanding of the relative impacts of different livestock systems and landscape structure on biodiversity. Here, we provide the first empirical and multi‐scale assessment of the relative effects of livestock intensification and landscape structure on biodiversity in the threatened tropical dry forests of Mesoamerica.

We used a dataset of dung beetles (169,372 individuals from 33 species) collected from 20 1‐km2 landscapes, ranging from zero‐yielding forest sites to high‐yield cattle ranches and maize farms, to investigate the relative effect of livestock intensification (net cattle production; macrocyclic lactone use; annual dung production) and landscape structure (landscape composition and configuration) at multiple spatial scales on different attributes of dung beetle communities using a multi‐model averaging approach.

Dung beetle species richness, biomass and composition were more strongly related to landscape structure than to livestock intensification.

Forest cover was the best predictor of dung beetle assemblages, being positively related to species diversity and biomass across multiple spatial scales. The use of macrocyclic lactones was strong and negatively related to dung beetle communities at the local scale.

Synthesis and applications: Maximising forest protection through a “land sparing” strategy is likely to be the best strategy for reducing negative impacts of cattle farming on Neotropical dung beetle communities. However, increasing or maintaining yields while reducing agrochemical inputs will be important for conserving on‐farm biodiversity and the ecosystem services that dung beetles provide in livestock‐dominated landscapes.
Biodiversity change is uncoupled from species richness trends: Consequences for conservation and monitoring
Authors: Hillebrand Helmut , Blasius Bernd , Borer Elizabeth T. , Chase Jonathan M. , Downing John A. , Eriksson Britas Klemens , Filstrup Christopher T. , Harpole W. Stanley , Hodapp Dorothee , Larsen Stefano , Lewandowska Aleksandra M. , Seabloom Eric W. , Van de Waal Dedmer B. , Ryabov Alexey B.
Published: June 2017

Global concern about human impact on biological diversity has triggered an intense research agenda on drivers and consequences of biodiversity change in parallel with international policy seeking to conserve biodiversity and associated ecosystem functions. Quantifying the trends in biodiversity is far from trivial, however, as recently documented by meta‐analyses, which report little if any net change in local species richness through time.

Here, we summarise several limitations of species richness as a metric of biodiversity change and show that the expectation of directional species richness trends under changing conditions is invalid. Instead, we illustrate how a set of species turnover indices provide more information content regarding temporal trends in biodiversity, as they reflect how dominance and identity shift in communities over time.

We apply these metrics to three monitoring datasets representing different ecosystem types. In all datasets, nearly complete species turnover occurred, but this was disconnected from any species richness trends. Instead, turnover was strongly influenced by changes in species presence (identities) and dominance (abundances). We further show that these metrics can detect phases of strong compositional shifts in monitoring data and thus identify a different aspect of biodiversity change decoupled from species richness.

Synthesis and applications: Temporal trends in species richness are insufficient to capture key changes in biodiversity in changing environments. In fact, reductions in environmental quality can lead to transient increases in species richness if immigration or extinction has different temporal dynamics. Thus, biodiversity monitoring programmes need to go beyond analyses of trends in richness in favour of more meaningful assessments of biodiversity change.
A dual role for farmlands: food security and pollinator conservation
Authors: Burkle Laura A. , Delphia Casey M. , O'Neill Kevin M.
Published: June 2017

We briefly review current understanding of wild pollinators and pollination services on farmlands.

We consider how concepts in plant ecology – community assembly and functional trait diversity ‐ may be applied to create diverse, wild pollinator communities across scales in agroecosystems.

We also make recommendations for best practices to enhance pollination services and create more sustainable food production systems under changing environmental conditions, including creating greater landscape connectivity, embracing pollinator dynamics, and providing incentives and other motivations to support these practices.

Synthesis. We highlight the opportunity for agricultural lands to serve a dual role for both food production and pollinator conservation, and conclude by posing unanswered questions and top priorities for future studies.
Conditions on Iterative Rounding Harmony in Oroqen
Authors: Dresher B. Elan , Nevins Andrew
Published: June 2017

In this paper, we re‐examine the claim that Baiyinna Oroqen, a language of the Tungusic family with a largely predictable distribution of non‐high round vowels, requires a non‐iterative type of rounding harmony, by demonstrating instead the need for a clear distinction between stem‐internal morpheme structure constraints and suffixal vowel harmony. We also propose to revise what was thought to be a requirement that harmony donors must be anchored in two successive syllables; it is instead a restriction that copying of the harmonic feature must be from the closest non‐initial vowel.
Wicked problems in special and inclusive education
Authors: Armstrong David
Published: June 2017

This special paper provides a critical overview of wicked problems in special and inclusive education. Practically, this paper provides a strategic framework for future special issues in the Journal of Special Educational Needs. Critical attention is also given to the concept of a wicked problem when applied to research in special and inclusive education: the suggestion is made this focus can stimulate innovations necessary for educational change and begin the process through which key problems in the field are addressed. A final observation made is that tangible change is unlikely to occur in special and inclusive education without addressing the underpinning beliefs and behavioural motivations which sustain today's wicked problems. Systematic transformation is therefore unlikely to be sustained without disruptive attention to the psychological, cultural and political aspects of ‘the way things are’.
ROMAN LAW AND THE TWO LANGUAGES IN JUSTINIAN'S EMPIRE
Authors: CORCORAN SIMON
Published: June 2017

This paper, reflecting Fergus Millar's work on linguistic and cultural diversity in the Roman empire, surveys the evolving relationship of Latin and Greek as languages for Roman law. Normative texts remained predominantly Latin until the completion of Justinian's codification (534), even though that was a genuinely bilingual product. However, following the already existing pattern in the Greek east, a vast corpus of Greek materials was then quickly created to teach the codification in the official law schools. Designed to aid engagement with the source-texts, these ended up superseding them. Roman legal Greek, a mixture of Latin terminology plus standardized Greek vocabulary, became stabilized. After 534, new legislation was most often in Greek, necessitating parallel Latin materials to help Latin-speaking students, although sixth-century collections of Novels (‘new laws’) were still bilingual. In practice, however, in most of Justinian's empire, a lawyer (such as Dioscorus of Aphrodito) could function with limited Latin. Soon Roman law would bifurcate into two monolingual traditions, Greek in the east, Latin in the west.
Intrathecal dexamethasone vs. meperidine for prevention of shivering during transurethral prostatectomy: a randomized controlled trial
Authors: Moeen S. M. , Moeen A. M.
Published: June 2017

Background

Shivering is a common complication after spinal anesthesia. Also, during transurethral prostatectomy a large amount of irrigating fluids is used which may cause hypothermia and shivering. We hypothesized that intrathecal dexamethasone could effectively attenuate post‐spinal shivering following transurethral prostatectomy as intrathecal meperidine.

Methods

Ninety male patients, ASA II‐III, 50–75 years old were included in this prospective and randomized double‐blind study. Patients were divided into three equal groups; Group D received 8 mg dexamethasone, Group M received 0.2 mg/kg meperidine, and Group C received 2 ml of normal saline, each in addition to intrathecal hyperbaric bupivacaine 0.5%. Shivering incidence, intensity and recurrence, dose of IV meperidine required to treat shivering, and adverse events were recorded for 150 min after the start of spinal anesthesia.

Results

The number of patients with shivering was higher in Group C (13) than in Group D (2) and Group M (3) with no differences between Group D and M; P = 0.001. Intensity and recurrence of shivering and dose of IV meperidine used to treat shivering were higher in Group C compared to Group D and Group M; P = 0.01, P = 0.064, and P = 0.004, respectively. Adverse events were not different between groups except sedation and pruritus which occurred only in Group M compared to Group D and Group C; P = 0.005 and P = 0.001, respectively.

Conclusion

Intrathecal dexamethasone was as effective as intrathecal meperidine in attenuation of shivering compared to placebo in patients scheduled for prostate surgery under spinal anesthesia with less adverse events.
Delivery parameters, neonatal parameters and incidence of urinary incontinence six months postpartum: a cohort study
Authors: Wesnes Stian Langeland , Hannestad Yngvild , Rortveit Guri
Published: June 2017

Introduction

Contradictory results have been reported regarding most delivery parameters as risk factors for urinary incontinence. We investigated the association between the incidence of urinary incontinence six months postpartum and single obstetric risk factors as well as combinations of risk factors.

Material and methods

This study was based on the Norwegian Mother and Child Cohort Study, conducted by the Norwegian Institute of Public Health during 1998–2008. This substudy was based on 7561 primiparous women who were continent before and during pregnancy. Data were obtained from questionnaires answered at weeks 15 and 30 of pregnancy and six months postpartum. Data were linked to the Medical Birth Registry of Norway. Single and combined delivery‐ and neonatal parameters were analyzed by logistic regression analyses.

Results

Birthweight was associated with significantly higher risk of urinary incontinence six months postpartum [3541–4180 g: odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2–1.6; >4180 g: OR 1.6, 95% CI 1.2–2.0]. Fetal presentation, obstetric anal sphincter injuries, episiotomy and epidural analgesia were not significantly associated with increased risk of urinary incontinence. The following combinations of risk factors among women delivering by spontaneous vaginal delivery increased the risk of urinary incontinence six months postpartum; birthweight ≥3540 g and ≥36 cm head circumference; birthweight ≥3540 g and forceps, birthweight ≥3540 g and episiotomy; and ≥36 cm head circumference and episiotomy.

Conclusion

Some combinations of delivery parameters and neonatal parameters seem to act together and may increase the risk of incidence of urinary incontinence six months postpartum in a synergetic way.
Competing knowledge systems and adaptability to sea‐level rise in The Bahamas
Authors: Petzold Jan , Ratter Beate M. W. , Holdschlag Arnd
Published: June 2017

In times of climate change and global ecosystem degradation, Small Island Developing States (SIDS) are both showcases and indicators for global social‐ecological dynamics. Resilience is among the most prominent concepts to assess and improve communities’ capacity to adapt to environmental changes, described as adaptability. But how environmental pressures are perceived, and how this perception translates into action and specific behavioural patterns, is regionally different and depends on cultural, historical and cognitive contexts. Within the cultural and regional framing, different knowledge systems can be identified, which affect perception of and behaviour towards environmental concerns. Knowledge systems can be competing, because they are influenced by different and changing cultural identities, experiences, worldviews, norms and (unequal) power relations. How do competing knowledge systems influence adaptability? And how can we learn from them, respectively? By means of qualitative and quantitative empirical research on The Bahamas, we show how different knowledge systems translate into different modes of responding to specific environmental pressures, such as sea‐level rise. The understanding of historicity and temporality, experience and learning processes, and institutional settings, which frame people's knowledge of their environment, is important for understanding potentials for adaptability.
What shapes cerambycid beetle communities in a tropical forest mosaic? Assessing the effects of host tree identity, forest structure, and vertical stratification
Authors: Li Lin , Aguilar Reinaldo , Berkov Amy
Published: June 2017

Due to anthropogenic activities, tropical rain forests face many challenges in sustaining biodiversity and maintaining global climates. This study explores how forest successional stage, tree composition, and stratum affect communities of saproxylic cerambycid beetles—concealed feeders that play important roles in forest nutrient cycling. Forty trees in five families (Fabaceae, Lecythidaceae, Malvaceae, Moraceae, and Sapotaceae) were sampled in a mosaic of old‐growth and secondary forest on the Osa Peninsula, Costa Rica. Bait branches yielded 3549 cerambycid individuals in 49 species. Species richness was almost identical in old‐growth and secondary forest, and both yielded specialists, but abundance was higher in old‐growth forest. Overall community structure was most strongly influenced by host plant species; within most plant families it was also impacted by forest successional status. Moraceae was the exception, presumably because the focal tree species was abundant in both old‐growth and secondary forest. Several host and old‐growth specialist species reached high densities within patches of old‐growth forest, but seldom colonized apparently suitable trees within secondary forest. This suggests that even small areas of old‐growth forest can act as refuges, but that secondary forest may act as a barrier to dispersal. The vulnerability of specialized saproxylic insects to land use change will be linked to the ability of their preferred hosts to disperse to and persist in successional habitats; rearing studies may provide the most accurate method to monitor community changes over time.
A Longitudinal Analysis of Well‐Being of Ghanaian Children in Transnational Families
Authors: Cebotari Victor , Mazzucato Valentina , Appiah Ernest
Published: June 2017

This study is the first to employ panel data to examine well‐being outcomes—self‐rated health, happiness, life satisfaction, and school enjoyment—of children in transnational families in an African context. It analyzes data collected in 2013, 2014, and 2015 from secondary schoolchildren and youth (ages 12–21) in Ghana (N = 741). Results indicate that children with fathers, mothers, or both parents away and those cared for by a parent, a family, or a nonfamily member are equally or more likely to have higher levels of well‐being as children in nonmigrant families. Yet, there are certain risk factors—being a female, living in a family affected by divorce or by a change in caregiver while parents migrate—that may decrease child well‐being.
Prolactinomas diagnosed in the postmenopausal period: Clinical phenotype and outcomes
Authors: Santharam Sandhya , Tampourlou Metaxia , Arlt Wiebke , Ayuk John , Gittoes Neil , Toogood Andrew , Webster Rachel , Karavitaki Niki
Published: June 2017

Objective

Most prolactinomas in females are diagnosed during the reproductive age, and the majority are microadenomas. Prolactinomas detected in the postmenopausal period are less common with limited published data on their presentation and prognosis. Our objective was to assess the presenting clinical, biochemical and imaging findings, as well as the outcomes of women diagnosed with a prolactinoma in the postmenopausal period.

Design and methods

We undertook a retrospective cohort study of women diagnosed with prolactinoma after menopause and followed up in a large UK pituitary centre. Information on presentation, management and outcomes was collected.

Results

Seventeen women with a median age at diagnosis of 63 years (range 52‐78) were identified. Headaches and/or visual deterioration were the most commonly reported complaints at detection of the adenoma (47%). Acute pituitary apoplexy was diagnosed at presentation or during follow‐up in 18% of the cases. The median serum prolactin was 12 364 mU/L (range 2533‐238 479). Macroprolactinomas comprised 94% of the tumours, and 88% of them had supra/parasellar extension. All patients with macroprolactinoma were offered dopamine agonist, and normal prolactin was achieved in 94% of them (median follow‐up 91.5 months). Adenoma shrinkage was observed in all women. Improvement or resolution of visual disturbances documented at presentation was observed in 86% of cases.

Conclusions

The clinical phenotype of prolactinomas diagnosed in the postmenopausal period is characterized by dominance of macroadenomas, with frequent supra/parasellar extension and a relative high rate of acute pituitary apoplexy. In this group of patients, the response of the macroadenomas to dopamine agonists is good.
Predictors for secondary therapy after surgical resection of nonfunctioning pituitary adenomas
Authors: Ratnasingam Jeyakantha , Lenders Nele , Ong Benjamin , Boros Samuel , Russell Anthony W. , Inder Warrick J. , Ho Ken K.Y.
Published: June 2017

Objective

Factors determining recurrence of nonfunctioning pituitary adenomas (NFAs) that require further therapy are unclear as are postoperative follow‐up imaging guidelines. We aimed to identify predictors for secondary therapy after surgical resection of NFAs and use this knowledge to inform postoperative management.

Design and patients

A single‐centre retrospective study of surgically resected NFAs in 108 patients followed for up to 15 years. Serial tumour images were analysed for size, location and growth rate (GR) and tissue analysed for hormone cell type and proliferation indices with secondary treatment as outcome measure.

Results

Twenty‐four of 66 (36%) patients harbouring a postoperative remnant required secondary treatment, all occurring within 10 years. No secondary treatment was required in any of 42 patients with complete tumour resection. Age, gender, remnant volume and tumour histology were not different between patients requiring and not requiring secondary therapy. Remnant GRs in those requiring secondary therapy were more than 10‐fold higher (P<.01). Tumours with a GR ≥80 mm3/y (Hazard Ratio[HR]: 8.1, Confidence Interval [CI]: 2.4‐27.3,P<.01) and those located in the suprasellar region (HR: 6.1, CI: 1.1‐32, P=.03) had a higher risk for secondary therapy. Tumour GR in the first three postoperative years correlated significantly (r2=.6, P<.01) with GR during the period of follow‐up.

Conclusion

In surgically resected NFAs further treatment is dependent on the presence of residual tumour, growth rate and location but not tumour histology. Postoperative growth rate of NFAs in the first 3 years of imaging can be used to tailor long‐term follow‐up to optimize use of health resources.
Random skin biopsy in the diagnosis of intravascular lymphoma
Authors: Sitthinamsuwan Panitta , Chinthammitr Yingyong , Pattanaprichakul Penvadee , Sukpanichnant Sanya
Published: June 2017

Background

Random skin biopsy (RSB) is a method for diagnosis of intravascular lymphoma (IVL). However, the indications for RSB to diagnose IVL have not yet been established. The aim of this study was to determine the appropriate indications for RSB to diagnose IVL.

Methods

Thirty‐two patients with fever of unknown origin (FUO) and without skin lesion underwent RSB for diagnosis of IVL. Clinical data, including fever, neurological symptoms, hematologic disorders, organomegaly, bone marrow (BM) study, hypoxemia and serum level of lactate dehydrogenase (LDH), were evaluated.

Results

Seven of 32 patients were definitively diagnosed with IVL. In addition to FUO, 2 IVL patients also suffered from dyspnea and neurological disorders. Patients who had FUO with accompanying hematologic disorders, high LDH, negative BM study and no lymphadenopathy or hepatosplenomegaly had a significant tendency to have IVL by RSB (P = .03). FUO with hypoxemia was also identified as a significant indication for RSB (P = .02).

Conclusions

RSB is a reliable method for diagnosis of IVL, especially in patients with FUO and any 1 or more of the 4 following abnormalities: (1) hematologic abnormalities; (2) high serum LDH; (3) hypoxemia; and/or, (4) unusual neurological symptoms with co‐existing hematologic abnormalities and without lymphadenopathy, hepatosplenomegaly or BM abnormality.
Polo‐like kinase‐1 immunoreactivity is associated with metastases in cutaneous melanoma
Authors: Kaczorowski Maciej , Borowiec Tomasz , Donizy Piotr , Pagacz Konrad , Fendler Wojciech , Lipinski Artur , Halon Agnieszka , Matkowski Rafal
Published: June 2017

Background

Polo‐like kinase‐1 (PLK‐1) is one of the key regulators of cell cycle progression. Increased expression of PLK‐1 was observed in several tumor types.

Methods

We immunohistochemically assessed PLK‐1 expression in neoplastic and stromal compartments of 96 cutaneous melanomas, and analyzed associations between PLK‐1 expression and clinicopathological characteristics.

Results

PLK‐1 expression in cancer cells was not associated with basic clinical (eg, age, gender and tumor location) or histopathological (eg, Breslow thickness, mitotic rate and ulceration) parameters. However, increased PLK‐1 was more frequent in tumors with concurrent regional nodal metastases and positive sentinel lymph node biopsy status. All primary tumors associated with co‐existing distant metastases exhibited high PLK‐1 expression in melanoma cells. Conversely, PLK‐1 expression in stromal cells was more frequent in tumors without nodal metastases. PLK‐1 expression in both compartments was not associated with survival.

Conclusion

PLK‐1 expression is associated with metastatic potential in cutaneous melanoma.
Developing Local Narratives for Objects in National Collections: Lessons Learned from the “Number Please? Working with the Enfield Exchange” Project
Authors: Geoghegan Hilary , McIlvenna Kathleen , van der Vaart Merel
Published: June 2017

Museums of science, technology, and engineering are developing new ways of interpreting and displaying their collections. Increasingly objects are being placed within narratives of everyday use; the human side of technology. The focus of this article is a section of one of the last UK manual telephone switchboards, which was acquired by the Science Museum, London, following its decommissioning in 1960. This artifact offers a unique insight into a communication technology that relied extensively on female telephonists, a distinct way of understanding gender roles in the twentieth century. The authors explore strategies for developing local narratives for objects from national collections and reflect on lessons learned from a cross‐institutional collaboration. This article highlights: the value of local historians, community events and oral histories to developing local narratives; how these activities informed understandings of the telephone switchboard; work life in the communications industry; the relationship between women and technology; and practical strategies that can enhance collections and museum practice through collaboration.
Research and Practice: One Way, Two Way, No Way, or New Way?
Authors: Bevan Bronwyn
Published: June 2017

As learning institutions, museums have long been buffeted by currents, coming mostly out of formal education, defining what counts as learning. The field has struggled to find its way in these waters. In this article I propose a strategy for gaining a firmer footing and indeed (shifting metaphors) for beginning to shape the very landscape, in educational and cultural policy, that currently constrains how our work is perceived and understood as contributing to learning within broader educational ecosystems. Research‐practice partnerships represent a new, more equitable and perhaps more ethical, strategy for producing evidence‐based knowledge and practice. Leveraging perspectives and expertise of both researchers and museum practitioners, RPPs can help the field begin to redefine what learning looks like and how museums both support and expand it. This paper discusses the need to participate in this new approach to research and provides some strategies for getting started.
Characterizing private investments and implications for poverty reduction and natural resource management in Laos
Authors: Keovilignavong Oulavanh , Suhardiman Diana
Published: June 2017

We examine the patterns and characteristics of private investment in Laos, and how these evolve in relation to the Lao government's investment incentive policies in particular, and the wider State policies in general. Our goals are to: (1) systematically describe and analyze the patterns and characteristics of private investment in the country, and (2) analyze investment outcomes in terms of economic growth, poverty reduction and livelihoods. We argue that while private investments in the resource sector have contributed to economic growth, they have also negatively impacted local resources and communities. From a policy perspective, we highlight the need to examine the actual significance of policy incentives provided by the Lao government, especially with regard to its ability to direct investment decisions, in terms of both geography and sector.
Gestation length and racing performance in 115 Thoroughbred foals with incomplete tarsal ossification
Authors: Haywood L. , Spike‐Pierce D. L. , Barr B. , Mathys D. , Mollenkopf D.
Published: June 2017

Background

Incomplete ossification of the cuboidal bones of the carpus and tarsus in foals has the potential for significant consequences including chronic lameness and decreased athletic ability.

Objectives

To determine if the degree of ossification of the cuboidal bones is associated with gestational length and if the diagnosis of incomplete ossification is a predictor of performance in Thoroughbred racehorses.

Study design

Retrospective cohort study.

Methods

The medical records of Thoroughbred foals less than 90 days of age from 1994 to 2011 were examined and records containing tarsal radiographs identified. Radiographs of the tarsus were examined for signs of incomplete ossification and those that were incompletely ossified graded on a scale of 1–4 using a modification of a previously reported index, with Grade 1 being the least ossified and Grade 4 being the most. Gestational length was determined by examining breeding records and foaling dates reported to the Jockey Club. Race records for 2‐ and 3‐year‐old affected foals and their maternal siblings were obtained and compared.

Results

Foals with Grades 1 and 2 ossification were usually premature (gestation length <325 days), but Grades 3 and 4 were not. Foals with Grades 2 and 3 ossification were significantly less likely to race than their maternal siblings and Grades 1, 2, 3 and 4 foals earned less money.

Main limitations

A larger sample size of foals with Grade 1 ossification would increase the power of the study. Foals radiographed at an older age may have had lower ossification scores if radiographed earlier.

Conclusions

Incomplete ossification, especially Grades 1 and 2, is associated with a short gestation length. Foals with Grades 2 and 3 incomplete ossification were less likely to race and Grades 1, 2 and 3 earned around $30,000 less than their maternal siblings.
Structural studies of a hyperthermophilic thymidylate kinase enzyme reveal conformational substates along the reaction coordinate
Authors: Biswas Ansuman , Shukla Arpit , Chaudhary Santosh Kumar , Santhosh Rajendran , Jeyakanthan Jeyaraman , Sekar Kanagaraj
Published: June 2017

Thymidylate kinase (TMK) is a key enzyme which plays an important role in DNA synthesis. It belongs to the family of nucleoside monophosphate kinases, several of which undergo structure‐encoded conformational changes to perform their function. However, the absence of three‐dimensional structures for all the different reaction intermediates of a single TMK homolog hinders a clear understanding of its functional mechanism. We herein report the different conformational states along the reaction coordinate of a hyperthermophilic TMK from Aquifex aeolicus, determined via X‐ray diffraction and further validated through normal‐mode studies. The analyses implicate an arginine residue in the Lid region in catalysis, which was confirmed through site‐directed mutagenesis and subsequent enzyme assays on the wild‐type protein and mutants. Furthermore, the enzyme was found to exhibit broad specificity toward phosphate group acceptor nucleotides. Our comprehensive analyses of the conformational landscape of TMK, together with associated biochemical experiments, provide insights into the mechanistic details of TMK‐driven catalysis, for example, the order of substrate binding and the reaction mechanism for phosphate transfer. Such a study has utility in the design of potent inhibitors for these enzymes.

Database

Structural data are available in the PDB under the accession numbers 2PBR, 4S2E, 5H5B, 5XAI, 4S35, 5XB2, 5H56, 5XB3, 5H5K, 5XB5, and 5XBH.
The nucleotide‐free state of heterotrimeric G proteins α‐subunit adopts a highly stable conformation
Authors: Andhirka Sai Krishna , Vignesh Ravichandran , Aradhyam Gopala Krishna
Published: June 2017

Deciphering the mechanism of activation of heterotrimeric G proteins by their cognate receptors continues to be an intriguing area of research. The recently solved crystal structure of the ternary complex captured the receptor‐bound α‐subunit in an open conformation, without bound nucleotide has improved our understanding of the activation process. Despite these advancements, the mechanism by which the receptor causes GDP release from the α‐subunit remains elusive. To elucidate the mechanism of activation, we studied guanine nucleotide‐induced structural stability of the α‐subunit (in response to thermal/chaotrope‐mediated stress). Inherent stabilities of the inactive (GDP‐bound) and active (GTP‐bound) forms contribute antagonistically to the difference in conformational stability whereas the GDP‐bound protein is able to switch to a stable intermediate state, GTP‐bound protein loses this ability. Partial perturbation of the protein fold reveals the underlying influence of the bound nucleotide providing an insight into the mechanism of activation. An extra stable, pretransition intermediate, ‘empty pocket’ state (conformationally active‐state like) in the unfolding pathway of GDP‐bound protein mimics a gating system – the activation process having to overcome this stable intermediate state. We demonstrate that a relatively more complex conformational fold of the GDP‐bound protein is at the core of the gating system. We report capturing this threshold, ‘metastable empty pocket’ conformation (the gate) of α‐subunit of G protein and hypothesize that the receptor activates the G protein by enabling it to achieve this structure through mild structural perturbation.
Genetics of alcohol consumption in Drosophila melanogaster
Authors: Fochler S. , Morozova T. V. , Davis M. R. , Gearhart A. W. , Huang W. , Mackay T. F. C. , Anholt R. R. H.
Published: June 2017

Individual variation in alcohol consumption in human populations is determined by genetic, environmental, social and cultural factors. In contrast to humans, genetic contributions to complex behavioral phenotypes can be readily dissected in Drosophila, where both the genetic background and environment can be controlled and behaviors quantified through simple high‐throughput assays. Here, we measured voluntary consumption of ethanol in ∼3000 individuals of each sex from an advanced intercross population derived from 37 lines of the Drosophila melanogaster Genetic Reference Panel. Extreme quantitative trait loci mapping identified 385 differentially segregating allelic variants located in or near 291 genes at P < 10−8. The effects of single nucleotide polymorphisms associated with voluntary ethanol consumption are sex‐specific, as found for other alcohol‐related phenotypes. To assess causality, we used RNA interference knockdown or P{MiET1} mutants and their corresponding controls and functionally validated 86% of candidate genes in at least one sex. We constructed a genetic network comprised of 23 genes along with a separate trio and a pair of connected genes. Gene ontology analyses showed enrichment of developmental genes, including development of the nervous system. Furthermore, a network of human orthologs showed enrichment for signal transduction processes, protein metabolism and developmental processes, including nervous system development. Our results show that the genetic architecture that underlies variation in voluntary ethanol consumption is sexually dimorphic and partially overlaps with genetic factors that control variation in feeding behavior and alcohol sensitivity. This integrative genetic architecture is rooted in evolutionarily conserved features that can be extrapolated to human genetic interaction networks.
Factors associated with the difficulty in hospital acceptance among elderly emergency patients: A population‐based study in Osaka City, Japan
Authors: Matsuyama Tasuku , Kitamura Tetsuhisa , Katayama Yusuke , Kiyohara Kosuke , Hayashida Sumito , Kawamura Takashi , Iwami Taku , Ohta Bon
Published: June 2017

Aim

We aimed to investigate prehospital factors associated with difficulty in hospital acceptance among elderly emergency patients.

Methods

We reviewed ambulance records in Osaka City from January 2013 through December 2014, and enrolled all elderly emergency patients aged ≥65 years who were transported by on‐scene emergency medical service personnel to a hospital that the personnel had selected. The definition of difficulty in hospital acceptance was to the requirement for ≥4 phone calls to hospitals by emergency medical service personnel before receiving a decision from the destination hospitals. Prehospital factors associated with difficulty in hospital acceptance were examined through logistic regression analysis.

Results

During the study period, 72 105 elderly patients were included, and 13 332 patients (18.5%) experienced difficulty in hospital acceptance. In the simple linear regression model, hospital selection time increased significantly with an increasing number of phone calls (R2 = 0.774). In the multivariable analysis, older age (P for trend <0.001), calls from a healthcare facility (adjusted odds ratio [AOR] 1.23, 95% confidence interval [CI] 1.15–1.32), night‐time (AOR 2.17, 95% CI 2.08–2.26) and weekend/holidays (AOR 1.43, 95% CI 1.38–1.49) were significantly associated with difficulty in hospital acceptance. A positive association was observed between gastrointestinal emergency‐related symptoms and difficulty in hospital acceptance among elderly patients with symptoms of internal disease (AOR 1.71, 95% CI 1.53–1.91).

Conclusions

In Japan, which has a rapidly aging population, a comprehensive strategy for elderly emergency patients, especially for advanced age groups or nursing home residents, is required. Geriatr Gerontol Int 2017; 17: 2441–2448.
Platelet hyperaggregability is associated with decreased ADAMTS13 activity and enhanced endotoxemia in patients with acute cholangitis
Authors: Takaya Hiroaki , Kawaratani Hideto , Kubo Takuya , Seki Kenichiro , Sawada Yasuhiko , Kaji Kosuke , Okura Yasushi , Takeda Kosuke , Kitade Mitsuteru , Moriya Kei , Namisaki Tadashi , Mitoro Akira , Matsumoto Masanori , Fukui Hiroshi , Yoshiji Hitoshi
Published: June 2017

Aim

Insufficient ADAMTS13 activity (ADAMTS13:AC) leads to increased levels of unusually large von Willebrand factor (VWF) multimers and causes microcirculatory disturbance and multiple organ failure (MOF). Endotoxin (Et) triggers the activation of coagulation and cytokine cascades, leading to MOF in severe inflammatory response syndrome. Here, we investigated the potential role of endotoxemia‐related ADAMTS13 in acute cholangitis.

Methods

Twenty‐four patients with acute cholangitis, including 7 with severe acute cholangitis, were recruited in this study. The levels of ADAMTS13:AC, VWF antigen (VWF:Ag), interleukin (IL)‐6, IL‐8, and tumor necrosis factor (TNF)‐α in each patient were determined by enzyme‐linked immunosorbent assay, whereas Et levels were determined by Et activity assay (EAA) analysis.

Results

The ADAMTS13:AC and VWF:Ag levels were significantly lower and higher, respectively, in patients with acute cholangitis than in controls. The EAA levels were higher in patients with acute cholangitis than in controls, and were inversely correlated with that of ADAMTS13:AC. Patients with severe acute cholangitis had significantly lower ADAMTS13:AC and higher VWF:Ag levels than those with mild to moderate cholangitis. Notably, ADMTS13:AC was directly correlated with platelet counts and inversely correlated with IL‐6 levels, and the VWF:Ag/ADAMTS13:AC ratio was directly correlated with IL‐8 and TNF‐α levels.

Conclusions

Imbalance of ADAMTS13:AC and VWF:Ag levels might be associated with severe acute cholangitis, reflecting platelet hyperaggregability. Severe acute cholangitis has severe pathophysiological features and is complicated by endotoxemia and MOF. Notably, this is the first report indicating an association between the levels of ADAMTS13:AC and VWF:Ag and those of EAA and cytokines in acute cholangitis.