bluuebunny/crossref_metadata_2025 huggingface dataset:
Genes relocated betweenDrosophila chromosomearms evolve under relaxed selective constraints relative to non-relocated genes
Authors: Hart Margaret L. I. , Vu Ban L. , Bolden Quinten , Chen Keith T. , Oakes Casey L. , Zoronjic Lejla , Meisel Richard P.
Published: August 2017

Gene duplication creates a second copy of a gene either in tandem to the ancestral locus or dispersed to another chromosomal location. When the ancestral copy of a dispersed duplicate is lost from the genome, it creates the appearance that the gene was “relocated” from the ancestral locus to the derived location. Gene relocations may be as common as canonical dispersed duplications in which both the ancestral and derived copies are retained. Relocated genes appear to be under more selective constraints than the derived copies of canonical duplications, and they are possibly as conserved as single-copy non-relocated genes. To test this hypothesis, we combined comparative genomics, population genetics, gene expression, and functional analyses to assess the selection pressures acting on relocated, duplicated, and non-relocated single-copy genes inDrosophilagenomes. We find that relocated genes evolve faster than single-copy non-relocated genes, and there is no evidence that this faster evolution is driven by positive selection. In addition, relocated genes are less essential for viability and male fertility than single-copy non-relocated genes, suggesting that relocated genes evolve fast because of relaxed selective constraints. However, relocated genes evolve slower than the derived copies of canonical dispersed duplicated genes. We therefore conclude that relocated genes are under more selective constraints than canonical duplicates, but are not as conserved as single-copy non-relocated genes.
RNA-dependent intergenerational inheritance of enhanced synaptic plasticity after environmental enrichment
Authors: Benito Eva , Kerimoglu Cemil , Ramachandran Binu , Zhou Qihui , Pena Tonatiuh , Capece Vincenzo , Jain Gaurav , Burkhardt Susanne , Stilling Roman , Edbauer Dieter , Dean Camin , Fischer André
Published: August 2017

Physical exercise in combination with cognitive training is known to enhance synaptic plasticity, learning & memory and lower the risk for various complex diseases including Alzheimer’s disease. Here we show that exposure of adult male mice to an environmental enrichment paradigm leads to enhancement of synaptic plasticity and cognition also in the next generation. We show that the effect is mediated through sperm RNA and is explained by microRNAs 212/132. In conclusion, our study reports intergenerational inheritance of an acquired cognitive benefit and points to specific microRNAs as candidates mechanistically involved in this type of transmission.
Abnormal cell sorting underlies the unique X-linked inheritance ofPCDH19Epilepsy
Authors: Pederick Daniel T. , Richards Kay L. , Piltz Sandra G. , Mandelstam Simone A. , Dale Russell C. , Scheffer Ingrid E. , Gecz Jozef , Petrou Steve , Hughes James N. , Thomas Paul Q.
Published: August 2017

X-linked diseases typically exhibit more severe phenotypes in males than females. In contrast,Protocadherin 19(PCDH19) mutations cause epilepsy in heterozygous females but spare hemizygous males. The cellular mechanism responsible for this unique pattern of X-linked inheritance is unknown. We show that PCDH19 contributes to highly specific combinatorial adhesion codes such that mosaic expression ofPcdh19in heterozygous female mice leads to striking sorting between WT PCDH19- and null PCDH19-expressing cells in the developing cortex, correlating with altered network activity. Complete deletion of PCDH19 in heterozygous mice abolishes abnormal cell sorting and restores normal network activity. Furthermore, we identify variable cortical malformations in PCDH19 epilepsy patients. Our results highlight the role of PCDH19 in determining specific adhesion codes during cortical development and how disruption of these codes is associated with the unique X-linked inheritance ofPCDH19epilepsy.
Investigation of nanoparticulate silicon as printed layers using scanning electron microscopy, transmission electron microscopy, X-ray absorption spectroscopy and X-ray photoelectron spectroscopy
Authors: Unuigbe David M. , Harting Margit , Jonah Emmanuel O. , Britton David T. , Nordlund Dennis
Published: August 2017

The presence of native oxide on the surface of silicon nanoparticles is known to inhibit charge transport on the surfaces. Scanning electron microscopy (SEM) studies reveal that the particles in the printed silicon network have a wide range of sizes and shapes. High-resolution transmission electron microscopy reveals that the particle surfaces have mainly the (111)- and (100)-oriented planes which stabilizes against further oxidation of the particles. X-ray absorption spectroscopy (XANES) and X-ray photoelectron spectroscopy (XPS) measurements at the O 1s-edge have been utilized to study the oxidation and local atomic structure of printed layers of silicon nanoparticles which were milled for different times. XANES results reveal the presence of the +4 (SiO2) oxidation state which tends towards the +2 (SiO) state for higher milling times. Si 2p XPS results indicate that the surfaces of the silicon nanoparticles in the printed layers are only partially oxidized and that all three sub-oxide, +1 (Si2O), +2 (SiO) and +3 (Si2O3), states are present. The analysis of the change in the sub-oxide peaks of the silicon nanoparticles shows the dominance of the +4 state only for lower milling times.
The impact of global operations on product architecture: an exploratory study
Authors: Pashaei Sebastian , Olhager Jan
Published: August 2017

Purpose

The purpose of this paper is to explore how global operations of manufacturing companies influence the choice of product architecture decisions, ranging from integral to modular product designs.

Design/methodology/approach

The authors perform a multiple-case study of three global manufacturing companies with integral and modular product architectures.

Findings

The authors find that the internal network capabilities, the number of capable plants, the focus of component plants, the focus of assembly plants, the distances from key suppliers to internal plants, and the number of market segments significantly influence the choice of integral vs modular architecture.

Research limitations/implications

This study is limited to three large manufacturing companies with global operations. However, the authors investigate both integral and modular products. The authors develop propositions that can be tested in further survey research.

Practical implications

The findings show that the type of global operations network influences the decision on product architecture, such that certain global operations characteristics support integral product designs, while other characteristics support modular designs.

Originality/value

To the best of the authors’ knowledge this paper is the first study on the explicit impact of global operations on product architecture, rather than the other way around.
A multi-dimensional approach for managing open innovation in NPD
Authors: Bahemia Hanna , Squire Brian , Cousins Paul
Published: August 2017

Purpose

This paper explores openness within new product development (NPD) projects. The purpose of this paper is to examine the impact of breadth, depth and partner newness on product innovativeness and product competitive advantage. The authors also seek to examine the contingent effects of the appropriability regime. The authors make suggestions to academics and practitioners based on the findings.

Design/methodology/approach

The authors use a structured survey instrument producing an empirical analysis of 205 NPD projects in the manufacturing sector in the UK. The authors use an ordinary least squares regression model to test hypothesised relationships between openness (breadth, depth and partner newness), product innovativeness, product competitive advantage and the appropriability regime.

Findings

The authors find that each of the three dimensions of openness, depth, breadth and partner newness, have a significant but differing impact on product innovativeness. Specifically, the study indicates that breadth has a positive effect but only in the presence of a strong appropriability regime, partner newness has a direct positive effect, and depth a direct negative effect. The authors also find that product innovativeness has a positive impact on product competitive advantage.

Research limitations/implications

Further research should focus on replicating the findings in other countries, search for further moderating factors, such as the stage of the NPD process, and analyse the longitudinal impact of openness within NPD projects.

Practical implications

Organisations are encouraging managers to be more open in their approach to NPD. The authors’ findings suggest that managers need to think about the three dimensions of openness, breadth, depth and partner newness. Their engagement with each of these dimensions depends on the desired outcomes of the innovation project and the strength of patents.

Originality/value

The research extends the extant supplier involvement in new product development literature to examine the effect of up to 11 types of external actor in NPD projects. The authors test a new multi-dimensional measurement scale for the openness construct. The authors show that each dimension has a different relationship with product innovativeness.
Evaluating the effects of supply chain quality management on food firms’ performance
Authors: Song Hua , Turson Rabia , Ganguly Anirban , Yu Kangkang
Published: August 2017

Purpose

The purpose of this paper is to identify the two kinds of supply chain quality management (SCQM) capabilities: intra-SCQM and inter-SCQM, and explore the effect of intra- and inter-food SCQM on food safety and quality, and the effect of food SCQM on domestic and export performance through food certification and corporate reputation.

Design/methodology/approach

Secondary data on food selling or processing firms in Western China were collected to test all the hypotheses. The data were then analyzed using the statistical technique of stepwise regression and inference was drawn based on the result.

Findings

Through utilizing secondary data sources, it is found that intra-SCQM promotes sales in domestics market with mediating role of corporate reputation, while the realization of overseas performance depend both on intra- and inter-SCQM with mediating role of food certification.

Practical implications

The paper study on food supply chain quality problem, the suggested approaches can be easily realized by agro-food companies to achieve international competitiveness by implementing both intra- and inter-SCQM. Meanwhile to Chinese domestic companies, it is important to strengthen inter-SCQM and food certification in order to achieve competitive advantage.

Originality/value

Review of literature indicated that there is a dearth of open literature that discusses food safety from the perspective of inter- and intra-organizational management. Furthermore, it was also observed that there has been no study that has taken the safety signaling perspective. The current research tires to shed some light on this important, but sparely discussed issue.
An approach for speed limit determination for vehicle tracking in case of GID ambiguity and lack of information in navigation maps
Authors: Haliti Nusret , Kadriu Arbana , Jusufi Mensur
Published: August 2017

Purpose

The purpose of the research presented in this paper is about an algorithm used for speed limit determination, in cases when there is ambiguity in determining the correct road data for a tracked vehicle. This algorithm resolves the glitch that happens when emitted global positioning system (GPS) data are ambiguous regarding roads that are very near to each other. Furthermore, we give a solution for other difficulties regarding the speed limit involving accuracy of emitted data and lack of information in navigation maps.

Design/methodology/approach

Our vehicle tracking system parses all GPS data from different vehicles to a single centralized database. It uses balancers and parsers to parse these data. Balancers use algorithms like round-robin to choose between different parsers. Information gained by the GPS unit is parsed, and then sent to a central server at regular intervals. For the gained data, we try to analyze the speed limit problem when tracking vehicles, analyze the challenges that are linked with speed limit problem, define a solution for the above discussed drawbacks and measure the driving performance.

Findings

We have already developed a fully functioning tracking system, which uses the above-described algorithm in tracking of few hundred vehicles, which makes approximately 1,300,000 requests per day, resulting in more than 4,000,000 tracking records gained in six months. The system monitors the motion of different vehicles using the gained GPS data from the first hand. This monitoring is done by developing web and mobile applications for third-party actors. This monitoring regards not only to the raw-produced data but also to new metrics that are derived from the raw one.

Originality/value

To our knowledge, there is not a similar algorithm/technology that can be of help in case of geographical identifier (GID) ambiguity. This research presents a solution to a real problem that we faced and which could not be answered by any of the current algorithms and technologies regarding the speed limit. Therefore, we consider this paper as highly original, which brings value in the field of pervasive computing and machine-to-machine communication.
Innovation and imitation
Authors: Cheng Ya-Wen , Hsu Su-Ying , Lo Chu-Ping
Published: August 2017

Purpose

Third-party payments were first introduced by the US firm PayPal. Soon after, China developed a localized version of PayPal – Alipay, which became the main payment method for online transactions in China. Currently, the number of global transactions conducted with Alipay is three times that of PayPal. In addition to online transactions, Alipay also integrates with mobile payment applications to provide offline services, making physical transactions more convenient for users. The authors, in this paper, aim to address how third-party payments technology seems to be playing out an innovation-imitation-catch up story.

Design/methodology/approach

Krugman (1966) proposed a general-equilibrium model of product cycles under perfect competition where high-tech products are innovated by an “advanced” country and imitated by a “developing” country. The competition between US–China online technologies (e.g. third-party payments) seems to be playing out this innovation-imitation-catch up story.

Findings

The USA has already put a lot of effort into the operations of credit cards and checks, as well as other infrastructure such as human resources and installation of relevant systems. China lacks the infrastructure for payments made with credit cards and checks, and therefore China’s opportunity cost of moving directly from cash transactions to third-party payments is much less than that of the USA, which is why China holds follower advantage in third-party payment markets.

Originality/value

The third-party payment technologies appear to be a good example of the argument made by Krugman (1966) regarding the US–China competition on advanced technology, which states that an imitator can catch up with an inventor when the former acquires comparative advantages against the latter.
Questioning a “one size fits all” city brand
Authors: Zenker Sebastian , Braun Erik
Published: August 2017

Purpose

City branding has gained popularity as governance strategy. However, the academic underpinning is still poor, and city branding needs a more critical conceptualization, as well as more complex management systems. This paper challenges the use of a “one size fits all” city brand, which is still common practice in many places. The paper proposes that city branding involves much more complexity than is commonly thought and outlines a strategy that enables urban policy-makers, marketing researchers and (place) marketers alike to better deal with city branding.

Design/methodology/approach

The authors integrate insights from literature on place branding, brand architecture and customer-focused marketing.

Findings

The article argues that place brands (in general and communicated place brands in particular) are by definition very complex, due to their different target groups, diverse place offerings and various associations place customers could have. Thus, an advanced brand management including target group-specific sub-brands is needed.

Practical implications

The model will be helpful for place brand managers dealing with a diverse target audience, and is likely to improve the target group-specific communication.

Originality/value

The paper provides an insight into the complexity of city brands and acknowledges that the perception of city brands can differ considerably among different target groups. Additionally, it offers a more comprehensive definition of place brands. This will be helpful for city brand managers and researchers alike in dealing with city brand complexity.
Characterization of an anti‐varicella‐zoster virus compound that targets the portal protein encoded by ORF54
Authors: Yasui Ruka , Yoshida Chinatsu , Yamaguchi Toyofumi , Inoue Naoki
Published: August 2017

An anti‐varicella‐zoster virus compound, a 5‐chlorobenzo[b]thiophen derivative (45B5), was characterized. Its 50% effective concentration against the cell‐free vaccine Oka strain and 50% cytotoxic concentration in human fibroblasts were 16.9 µM and more than 100 µM, respectively. Treatment with 45B5 decreased viral DNA synthesis and IE62 expression weakly but significantly. All 45B5‐resistant viral clones isolated were found to have at least one mutation in ORF54 that encodes the portal protein. There were no effects on interaction between the portal and scaffold proteins. Thus, 45B5 may inhibit nuclear delivery of viral DNA.
Size‐dependent nutrient limitation of tree growth from subtropical to cold temperate forests
Authors: Li Yong , Tian Dashuan , Yang Hao , Niu Shuli
Published: August 2017

The traditional paradigm is that plant growth at high latitudes is generally nitrogen (N) limited, whereas phosphorus (P) limitation occurs at low latitudes. However, this latitudinal pattern of nutrient limitation is not empirically tested and the underlying mechanisms are far from clear.

Here we performed a coordinated experiment of N and/or P addition at three forest sites in China, a subtropical forest, a warm‐temperate forest and a cold‐temperate forest. By measuring relative growth rate (RGR) and leaf nutrient traits among different tree size groups, we assessed how they vary with nutrient addition and tree sizes and uncovered the likely mechanisms underlying these observed responses.

Our results revealed that P addition enhanced the RGR of small trees (DBH < 15 cm) by 41% in subtropical forest and 114% in warm‐temperate forest, but reduced it by 57% in cold‐temperate forest. Moreover, small tree RGR increased linearly with soil available P at subtropical and warm‐temperate sites, while it followed a quadratic relationship with soil available N:P ratio at a cold‐temperate site. N addition only affected small tree RGR at the cold‐temperate site. In contrast, the RGR of large trees (DBH > 15 cm) was not impacted by any nutrient addition treatment or soil nutrient variations at any site. Leaf P concentration and resorption efficiency in both small and large trees mostly showed a linear response to soil available P at subtropical and warm‐temperate sites, while leaf N:P ratio in small trees elevated linearly with soil available N:P ratio at a cold‐temperate site.

Overall, this study presents robust experimental evidence that growth in small trees, not large trees, is primarily limited by P in subtropical and warm‐temperate forests, but is co‐limited by N and P in cold‐temperate forests. This size‐dependent nutrient limitation highlights the importance of considering tree size classes when assessing nutrient limitation in forest.

A plain language summary is available for this article.
Leaf odour cues enable non‐random foraging by mammalian herbivores
Authors: Finnerty Patrick B. , Stutz Rebecca S. , Price Catherine J. , Banks Peter B. , McArthur Clare
Published: August 2017

Searching for food is the first critical stage of foraging, and search efficiency is enhanced when foragers use cues from foods they seek. Yet we know little about food cues used by one major group of mammals, the herbivores, a highly interactive component of most ecosystems. How herbivores forage and what disrupts this process, both have significant ecological and evolutionary consequences beyond the animals themselves.

Our aim was to investigate how free‐ranging mammalian herbivores exploit leaf odour cues to find food plants amongst a natural and complex vegetation community. Our study system comprised the native “deer equivalent” of eastern Australian forests, the swamp wallaby Wallabia bicolor, and seedlings of Eucalyptus, the foundation tree genus in these ecosystems. We quantified how foraging wallabies responded to odour cues from plants manipulated in several ways: varying the quantity of visually concealed leaves, comparing damaged vs. undamaged leaves, and whole plants vs. those with suppressed cues.

The rate of discovery of leaves by wallabies increased with odour cue magnitude, yet animals were extremely sensitive to even a tiny odour source of just a few leaves. Whole seedlings were discovered faster if their leaves were damaged. Wallabies found whole seedlings and those with suppressed visual cues equally rapidly, day and night. Seedlings with very little odour were discovered mainly by day, as nocturnal foraging success was severely disrupted.

This study shows how leaf odour attracts mammalian herbivores to food plants, enabling non‐random search for even tiny odour sources. As damaged leaves enhanced discovery, we suggest that the benefit of attracting natural enemies to invertebrate herbivores feeding on plants (potential “cry for help”) may be offset by a cost—increased browsing by mammalian herbivores. This cost should be incorporated into multi‐trophic plant–animal studies. Finally, the breakdown in capacity to find plants at night suggests substantial but unrecognized foraging costs to herbivores when abiotic factors, such as cold temperatures or pollution, reduce or degrade plant odour cues. We predict that an increasingly polluted world will alter the foraging success of mammalian herbivores, with significant ecological ramifications given that browsing can shape ecosystems.
Environmental controls on the causes and functional consequences of tree species diversity
Authors: Mori Akira S.
Published: August 2017

Knowledge of the functional consequences of biodiversity is increasing through studies of both experimental systems and natural systems. Community assembly theory has also helped to reveal the causes of biodiversity organization. However, the causes and consequences of biodiversity have been discussed in parallel and simultaneous consideration of both has been limited, even though they are both influenced by regional environmental conditions.

To understand the relationship between biodiversity and productivity, I focused on the linkages between the number of tree species and biomass productivity across forest biomes under a range of bioclimatic conditions.

I found that high tree diversity generally increased productivity. This was primarily due to a selection process that results from a high probability of having high‐performance species and their dominance at high diversity, regardless of the biome. In less‐productive biomes, the residual importance of diversity, which likely reflects other forms of biological interactions (including species complementarity), increased productivity.

These findings of differential diversity effects under different environmental conditions are consistent with the existing theory of community assembly, which predicts a shift in the assembly process from stochasticity to determinism with increasing environmental harshness. Analyses based on functional trait diversity also supported this theory: stochastic assembly (resulting in the selection effect) and deterministic assembly (possibly resulting from interspecific niche differences) became more important in productive and less‐productive biomes, respectively.

Synthesis. Increasing our understanding of the causalities between diversity and other characteristics, such as productivity, is crucial, particularly for forest ecosystems, because of the increasing interest in productivity‐related ecosystem services supported by diverse assemblages of trees.
Infectious and immunogenetic factors in bipolar disorder
Authors: Oliveira J. , Oliveira‐Maia A. J. , Tamouza R. , Brown A. S. , Leboyer M.
Published: August 2017

Objective

Despite the evidence supporting the association between infection and bipolar disorder (BD), the genetic vulnerability that mediates its effects has yet to be clarified. A genetic origin for the immune imbalance observed in BD, possibly involved in the mechanisms of pathogen escape, has, however, been suggested in recent studies.

Method

Here, we present a critical review based on a systematic literature search of articles published until December 2016 on the association between BD and infectious/immunogenetic factors.

Results

We provide evidence suggesting that infectious insults could act as triggers of maladaptive immune responses in BD and that immunogenetic vulnerability may amplify the effects of such environmental risk factors, increasing susceptibility to subsequent environmental encounters. Quality of evidence was generally impaired by scarce attempt of replication, small sample sizes and lack of high‐quality environmental measures.

Conclusion

Infection has emerged as a potential preventable cause of morbidity in BD, urging the need to better investigate components of the host–pathogen interaction in patients and at‐risk subjects, and thus opening the way to novel therapeutic opportunities.
Reduced incidence of neonatal early‐onset group B streptococcal infection after promulgation of guidelines for risk‐based intrapartum antibiotic prophylaxis in Sweden: analysis of a national population‐based cohort
Authors: Håkansson Stellan , Lilja Maria , Jacobsson Bo , Källén Karin
Published: August 2017

Introduction

This study aimed to investigate the incidence of neonatal early‐onset group B streptococcal (GBS) infection in Sweden after promulgation of guidelines (2008) for risk factor‐based intrapartum antibiotic prophylaxis, and evaluate the presence of risk factors and obstetric management in mothers.

Material and methods

National registers were searched for infants with early‐onset GBS infection during 2006–2011. Medical records of cases and case mothers were abstracted. Verified cases of sepsis/meningitis and cases with clinical sepsis/pneumonia were documented, as well as risk factors in case mothers and timeliness of intrapartum antibiotic prophylaxis administration.

Results

There were 227 cases with verified infection, with an incidence of 0.34‰ of live births during the whole period. There was a significant decrease after promulgation of guidelines, from 0.40 to 0.30‰ [odds ratio (OR) 0.75, 95% confidence interval (CI) 0.57–0.99]. A significant decrease in the number of cases with clinical GBS sepsis/pneumonia was also observed. In parturients with one or more risk factors, the incidence of any GBS infection was reduced by approximately 50% (OR 0.47, 95% CI 0.35–0.64), although there were many cases where the opportunity for timely administration of intrapartum antibiotic prophylaxis was missed. In infants of mothers without risk factor(s) there was no reduction in early‐onset GBS morbidity. The mortality in verified cases was 4.8% (95% CI 2.1–7.6).

Conclusions

The introduction of national guidelines for risk‐based intrapartum antibiotic prophylaxis coincided with a significant 50% risk reduction of neonatal early‐onset GBS infection in infants of parturients presenting with one or more risk factors. A stricter adherence to guidelines could probably have reduced the infant morbidity further.
Longitudinal transvaginal ultrasound evaluation of cesarean scar niche incidence and depth in the first two years after single‐ or double‐layer uterotomy closure: a randomized controlled trial
Authors: Bamberg Christian , Hinkson Larry , Dudenhausen Joachim W. , Bujak Verena , Kalache Karim D. , Henrich Wolfgang
Published: August 2017

Introduction

Cesarean deliveries are the most common abdominal surgery procedure globally, and the optimal way to suture the hysterotomy remains a matter of debate. The aim of this study was to assess the incidence of cesarean scar niches and the depth after single‐ or double‐layer uterine closure.

Material and methods

We performed a randomized controlled trial in which women were allocated to three uterotomy suture techniques: continuous single‐layer unlocked, continuous locked single‐layer, or double‐layer sutures. Transvaginal ultrasound was performed six weeks and 6–24 months after cesarean delivery [Clinicaltrials.gov (NCT02338388)].

Results

The study included 435 women. Six weeks after delivery, the incidence of niche was not significantly different between the groups (p = 0.52): 40% for single‐layer unlocked, 32% for single‐layer locked and 43% for double‐layer sutures. The mean ± SD niche depths were 3.0 ± 1.4 mm for single‐layer unlocked, 3.6 ± 1.7 mm for single‐layer locked and 3.3 ± 1.3 mm for double‐layer sutures (p = 1.0). There were no significant differences (p = 0.58) in niche incidence between the three groups at the second ultrasound follow up: 30% for single‐layer unlocked, 23% for single‐layer locked and 29% for double‐layer sutures. The mean ± SD niche depth was 3.1 ± 1.5 mm after single‐layer unlocked, 2.8 ± 1.5 mm after single‐layer locked and 2.5 ± 1.2 mm after double‐layer sutures (p = 0.61). There was a trend (p = 0.06) for the residual myometrium thickness to be thicker after double‐layer repair at the long‐term follow up.

Conclusions

The incidence of cesarean scar niche formation and the niche depth was independent of the hysterotomy closure technique.
More extended lymph node dissection template at radical prostatectomy detects metastases in the common iliac region and in the fossa of Marcille
Authors: Maderthaner Lydia , Furrer Marc A. , Studer Urs E. , Burkhard Fiona C. , Thalmann George N. , Nguyen Daniel P.
Published: August 2017

Objectives

To assess the effect of adding lymph nodes (LNs) located along the common iliac vessels and in the fossa of Marcille to the extended pelvic LN dissection (PLND) template at radical prostatectomy (RP).

Patients and Methods

A total of 485 patients underwent RP and PLND at a referral centre between 2000 and 2008 (historical cohort: classic extended PLND template) and a total of 268 patients between 2010 and 2015 (contemporary cohort: extended PLND template including LNs located along the common iliac vessels and in the fossa of Marcille). Descriptive analyses were used to compare baseline, pathological, complication and functional data between the two cohorts. A logistic regression model was used to assess the template's effect on the probability of detecting LN metastases.

Results

Of 80 patients in the historical cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 23 (29%), and the internal iliac in 18 (23%), while 39 patients (49%) had metastases in both locations. Of 72 patients in the contemporary cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 17 patients (24%), the internal iliac in 24 patients (33%), and the common iliac in one patient (1%), while 30 patients (42%) had metastases in >1 location (including fossa of Marcille in five patients). Among all 46 patients in the contemporary cohort with ≤2 metastases, three had one or both metastases in the common iliac region or the fossa of Marcille. The adjusted probability of detecting LN metastases was higher, but not significantly so, in the contemporary cohort. There were no differences between the two cohorts in complication rates and functional outcomes.

Conclusion

A more extended template detects LN metastases in the common iliac region and the fossa of Marcille and is not associated with a higher risk of complications; however, the overall probability of detecting LN metastases was not significantly higher.
Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?
Authors: Thom Maria , Liu Joan , Bongaarts Anika , Reinten Roy J. , Paradiso Beatrice , Jäger Hans Rolf , Reeves Cheryl , Somani Alyma , An Shu , Marsdon Derek , McEvoy Andrew , Miserocchi Anna , Thorne Lewis , Newman Fay , Bucur Sorin , Honavar Mrinalini , Jacques Tom , Aronica Eleonora
Published: August 2017

Multinodular and vacuolating neuronal tumor (MVNT) is a new pattern of neuronal tumour included in the recently revised WHO 2016 classification of tumors of the CNS. There are 15 reports in the literature to date. They are typically associated with late onset epilepsy and a neoplastic vs. malformative biology has been questioned. We present a series of ten cases and compare their pathological and genetic features to better characterized epilepsy‐associated malformations including focal cortical dysplasia type II (FCDII) and low‐grade epilepsy‐associated tumors (LEAT). Clinical and neuroradiology data were reviewed and a broad immunohistochemistry panel was applied to explore neuronal and glial differentiation, interneuronal populations, mTOR pathway activation and neurodegenerative changes. Next generation sequencing was performed for targeted multi‐gene analysis to identify mutations common to epilepsy lesions including FCDII and LEAT. All of the surgical cases in this series presented with seizures, and were located in the temporal lobe. There was a lack of any progressive changes on serial pre‐operative MRI and a mean age at surgery of 45 years. The vacuolated cells of the lesion expressed mature neuronal markers (neurofilament/SMI32, MAP2, synaptophysin). Prominent labelling of the lesional cells for developmentally regulated proteins (OTX1, TBR1, SOX2, MAP1b, CD34, GFAPδ) and oligodendroglial lineage markers (OLIG2, SMI94) was observed. No mutations were detected in the mTOR pathway genes, BRAF, FGFR1 or MYB. Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro‐glial cell type showing aberrant maturation.
Lipophilic conformationally constrained spiro carbocyclic 2,6‐diketopiperazine‐1‐acetohydroxamic acid analogues as trypanocidal and leishmanicidal agents: An extended SAR study
Authors: Zoidis Grigoris , Tsotinis Andrew , Tsatsaroni Alexandra , Taylor Martin C. , Kelly John M. , Efstathiou Antonia , Smirlis Despina , Fytas George
Published: August 2017

We have previously described a number of lipophilic conformationally constrained spiro carbocyclic 2,6‐diketopiperazine (2,6‐DKP)‐1‐acetohydroxamic acids as potent antitrypanosomal agents. In this report, we extend the SAR analysis in this class of compounds with respect to in vitro growth inhibition of Trypanosoma and Leishmania parasites. Introduction of bulky hydrophobic substituents at the vicinal position of the basic nitrogen atom in the spiro carbocyclic 2,6‐DKP ring system can provide analogues which are potently active against bloodstream form Trypanosoma brucei and exhibit significant activities toward Trypanosoma cruzi epimastogotes and Leishmania infantum promastigotes and intracellular amastigotes. In particular, compounds possessing a benzyl or 4‐chlorobenzyl substituent were found to be the most active growth inhibitors, with activities in the low nanomolar and low micromolar ranges for T. brucei and L. infantum, respectively. The benzyl‐substituted (S)‐enantiomer was the most potent derivative against T. brucei (IC50 = 6.8 nm), T. cruzi (IC50 = 0.21 μm), and L. infantum promastigotes (IC50 = 2.67 μm) and intracellular amastigotes (IC50 = 2.60 μm). Moreover, the (R)‐chiral benzyl‐substituted derivative and its racemic counterpart displayed significant activities against L. donovani. Importantly, the active compounds show high selectivity in comparison with two mammalian cell lines.
Sofosbuvir as treatment against dengue?
Authors: Gan Chye Sheng , Lim See Khai , Chee Chin Fei , Yusof Rohana , Heh Choon Han
Published: August 2017

Dengvaxia® (CTD‐TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD‐TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti‐HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS‐461203) was predicted to bind to the catalytic motif (Gly‐Asp‐Asp) of dengue viral polymerase with binding affinity of −6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC90 of 0.4 μm. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS‐461203 to exert its antidengue potential. All in all, sofosbuvir should be subjected to in‐depth studies to provide information of its efficacy toward dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue.
Lipopolysaccharide suppresses IgE‐mast cell‐mediated reactions
Authors: Wang N. , McKell M. , Dang A. , Yamani A. , Waggoner L. , Vanoni S. , Noah T. , Wu D. , Kordowski A. , Köhl J. , Hoebe K. , Divanovic S. , Hogan S. P.
Published: August 2017

Background

Clinical and experimental analyses have identified a central role for IgE/FcεRI/mast cells in promoting IgE‐mediated anaphylaxis. Recent data from human studies suggest that bacterial infections can alter susceptibility to anaphylaxis.

Objective

We examined the effect of LPS exposure on the induction of IgE‐mast cell (MC) mediated reactions in mice.

Methods

C57BL/6 WT, tlr4−/− and IL10−/− mice were exposed to LPS, and serum cytokines (TNF and IL‐10) were measured. Mice were subsequently treated with anti‐IgE, and the symptoms of passive IgE‐mediated anaphylaxis, MC activation, Ca2+‐mobilization and the expression of FcεRI on peritoneal MCs were quantitated.

Results

We show that LPS exposure of C57BL/6 WT mice constraints IgE‐MC–mediated reactions. LPS‐induced suppression of IgE‐MC–mediated responses was TLR‐4‐dependent and associated with increased systemic IL‐10 levels, decreased surface expression of FcεRI on MCs and loss of sensitivity to IgE activation. Notably, LPS‐induced desensitization of MCs was short term with MC sensitivity to IgE reconstituted within 48 hours, which was associated with recapitulation of FcεRI expression on the MCs. Mechanistic analyses revealed a requirement for IL‐10 in LPS‐mediated decrease in MC FcεRI surface expression.

Conclusions & Clinical Relevance

Collectively, these studies suggest that LPS‐induced IL‐10 promotes the down‐regulation of MC surface FcεRI expression and leads to desensitization of mice to IgE‐mediated reactions. These studies indicate that targeting of the LPS‐TLR‐4‐IL‐10 pathway may be used as a therapeutic approach to prevent adverse IgE‐mediated reactions.
Founder‐CEOs and corporate turnaround among declining firms
Authors: Abebe Michael A. , Tangpong Chanchai
Published: August 2017

Manuscript Type

Empirical

Research Question/Issue

Despite the growing interest in leaders' role in the turnaround process, there is a paucity of research on founder‐CEOs' role in achieving successful turnaround among declining firms. In this study, using insights from the organizational identification literature, we argue that founder‐CEOs play an important role in turnaround attempts due to their strong organizational commitment and psychological attachment to the declining firm as well as the relative absence of agency problem issues common among their non‐founder counterparts.

Research Findings/Insights

Using data from a matched pair sample of 142 US firms that experienced performance decline, we found that founder‐CEO leadership significantly increases turnaround success in declining firms. We also found that, among turnaround firms, those led by founder‐CEOs tend to put more emphasis on market‐based turnaround strategies, such as new product introductions, and less emphasis on retrenchment actions, such as divestments.

Theoretical/Academic Implications

Our findings contribute to corporate turnaround research by providing a more nuanced view of leaders' role in the turnaround process by specifically exploring the effect of founder CEO leadership. Furthermore, this study contributes to the turnaround literature by highlighting the strategic choices of founder‐CEO‐led firms and how these choices influence successful turnaround. Finally, by introducing organizational identification perspective, this study provides additional theoretical explanation of leadership antecedents of successful turnarounds.

Practitioner/Policy Implications

The findings of this study suggest that boards of directors, shareholders, and consultants who often participate in turnaround management should carefully consider retaining founder‐CEOs and endorsing their leadership during the turnaround process. Further, the findings provide turnaround specialists and other stakeholders with further understanding of not only the importance of product market strategies in the turnaround process but also founder‐CEOs' role in fostering such strategies.
Corpus callosum and bilateral motor performance after unilateral neonatal arterial ischemic stroke
Authors: Bekiesińska‐Figatowska Monika
Published: August 2017

This commentary is on the original article by Groeschel et al. on pages 1042–1048 of this issue.
Measuring communicative participation in population‐based samples of children with speech and language difficulties
Authors: Levickis Penny
Published: August 2017

This commentary is on the original article by Cunningham et al. on pages 1049–1055 of this issue.
HbA1c variability is associated with increased mortality and earlier hospital admission in people with Type 1 diabetes
Authors: Walker G. S. , Cunningham S. G. , Sainsbury C. A. R. , Jones G. C.
Published: August 2017

Aim

Despite evidence of morbidity, no evidence exists on the relationship between HbA1c variability and mortality in Type 1 diabetes. We performed an observational study to investigate whether the association between HbA1c variability and mortality exists in a population of people with Type 1 diabetes. As a secondary outcome, we compared onset of first hospital admission between groups.

Methods

People with Type 1 diabetes were identified for inclusion from the Scottish Care Information – Diabetes data set. This database includes data of all people known to have diabetes who live within Scotland. A survival analysis was carried out over a 47‐month period comparing two groups; group 1 with a HbA1c coefficient of variation (CV) above the median CV value, and group 2 with a CV below the median value. Time to death or first admission was also analysed. A Cox proportional hazard model was used to compare time to death, adjusting for appropriate covariables.

Results

Some 6048 individuals with Type 1 diabetes were included in the analysis. Median HbA1c CV was 7.9. The hazard ratio (HR) for mortality for those with an HbA1c CV above the median value is 1.5 over 47 months of follow‐up (P < 0.001). HR for survival to either the first admission to hospital or death for those with an HbA1c CV above the median value was 1.35 (95% confidence interval 1.25–1.45) over 730 days of follow‐up (P < 0.001).

Conclusion

Our results show that people with greater HbA1c variability have a higher rate of mortality and earlier hospital admission in Type 1 diabetes.
A novel echocardiographic hemodynamic classification of heart failure based on stroke volume index and left atrial pressure
Authors: Abbas Amr E. , Khoury Abdulla Rami , Aggrawal Anshul , Crile Jason , Lester Steven J. , Boura Judy
Published: August 2017

Background and Aim

Dividing patients with heart failure (HF) based solely on ejection fraction (EF) may over simplify the hemodynamic states of these patients. We describe a novel echo‐derived hemodynamic HF model based on flow (stroke volume index [SVI]) and left atrial pressure (E:E′) correlates.

Methods

A retrospective analysis of patients admitted with HF with both reduced (HFrEF) and preserved EF (HFpEF). Patients were subdivided into four hemodynamic groups based on echocardiographic SVI (< or ≥35 mL/m2) and E/E′ (≥ or <15). Group A: normal flow and normal filling pressure, Group B: normal flow but high filling pressure, Group C: low flow and low filling pressure, and Group D: low flow and high filling pressure.

Results

A total of 176 patients were enrolled, 123 patients had HFrEF and 53 patients had HFpEF. Baseline characteristics were not statistically significant in both groups. In HFrEF, most patients were in group D compared to a heterogeneous distribution in HFpEF (P<.0001). In HFrEF, there was a trend toward an increase in B‐type natriuretic peptide levels with a decrease in SVI and increase in E/E′ (P=.05) but not in HFpEF. There was no difference in death, major adverse cardiac events, but a higher readmissions rate in the HFpEF group at 30 days and 18 months.

Conclusions

Hemodynamic subgroups differ between HFrEF and HFpEF. There is no difference in major adverse cardiovascular events between both groups with increased readmissions in HPpEF patients. Larger studies may help assess the impact of echo‐derived hemodynamic state on clinical outcome.
Distress and unmet needs during treatment and quality of life in early cancer survivorship: A longitudinal study of haematological cancer patients
Authors: Oberoi Devesh V. , White Victoria M. , Seymour John F. , Prince H. Miles , Harrison Simon , Jefford Michael , Winship Ingrid , Hill David J. , Bolton Damien , Millar Jeremy , Wong Doo Nicole , Kay Anne , Giles Graham
Published: August 2017

Objective

To examine the influence of anxiety, depression and unmet supportive care needs on future quality of life (QoL) in multiple myeloma (MM) and diffuse large B‐cell lymphoma (DLBCL) patients.

Methods

Multiple myeloma and DLBCL patients recruited through the population‐based Victorian Cancer Registry. Data were collected through two telephone interviews: (T1) on average 7 months postdiagnosis, (T2) average 8 months later. QoL was examined at T2 using the Functional Assessment of Cancer Therapy (FACT‐G) scale. The Hospital Anxiety and Depression Scale measured anxiety and depression, and the Supportive Care Needs Survey measured unmet needs at T1. Multivariate linear regression examined associations between QoL subscales (physical, emotional, social and functional well‐being and overall QoL) and T1 anxiety, depression and unmet needs.

Results

Except physical well‐being, all other QoL subscales and overall QoL were significantly associated with T1 anxiety. All QoL subscales and overall QoL were significantly associated with T1 depression. Only patient care needs were associated with physical and social well‐being and overall QoL.

Conclusion

Anxiety, depression and patient care unmet needs during treatment are associated with diminished physical and emotional well‐being in the following months. Psychological distress and unmet supportive care needs experienced during treatment should be addressed to maximise future QoL.