bluuebunny/crossref_metadata_2025 huggingface dataset:
iCAGES: integrated CAncer GEnome Score for comprehensively prioritizing cancer driver genes in personal genomes
Authors: Dong Chengliang , Yang Hui , He Zeyu , Liu Xiaoming , Wang Kai
Published: February 2015

All cancers arise as a result of the acquisition of somatic mutations that drive the disease progression. A number of computational tools have been developed to identify driver genes for a specific cancer from a group of cancer samples. However, it remains a challenge to identify driver mutations/genes for an individual patient and design drug therapies. We developed iCAGES, a novel statistical framework to rapidly analyze patient-specific cancer genomic data, prioritize personalized cancer driver events and predict personalized therapies. iCAGES includes three consecutive layers: the first layer integrates contributions from coding, non-coding and structural variations to infer driver variants. For coding mutations, we developed a radial support vector machine using manually curated mutations to predict their driver potential. The second layer identifies driver genes, by using information from the first layer and integrating prior biological knowledge on gene-gene and gene-phenotype networks. The third layer prioritizes personalized drug treatment, by classifying potential driver genes into different categories and querying drug-gene databases. Compared to currently available tools, iCAGES achieves better performance by correctly classifying point coding driver mutations (AUC=0.97, 95% CI: 0.97-0.97, significantly better than the second best tool with P=0.01) and genes (AUC=0.93, 95% CI: 0.93-0.94, significantly better than MutSigCV with P<1×10−15). We also illustrated two examples where iCAGES correctly nominated two targeted drugs for two advanced cancer patients with exceptional response, based on their somatic mutation profiles. iCAGES leverages personal genomic information and prior biological knowledge, effectively identifies cancer driver genes and predicts treatment strategies. iCAGES is available athttp://icages.usc.edu.
Relationship between tumor grade and geometrical complexity in prostate cancer
Authors: Llanos-Pérez J.A. , Tejera-Puente E. , Izquierdo-Kulich E. , Betancourt Mar J.A. , Nistal M. , González-Peramato P. , Royuela-García M. , Nieto-Villar J.M. , De Miguel M. P.
Published: February 2015

Prostate cancer exhibits high mathematical complexity due to the disruption of tissue architecture. An important part of the diagnostic of prostate tumor samples is the histological evaluation of cellular and glandular organization. The Gleason grade and score, a commonly used prognostic indicator of patient outcome, is based on the match of glandular architectural patterns with standard patterns. Unfortunately, the subjective nature of visual grading leads to variations in scoring by different pathologists. We proposed the fractal dimension of the lumen and the Lempel-Zip complexity of the histopathological patterns as useful descriptors aiding pathologist to standardize histological classification and thus prognosis and therapy planning.

Highlights

geometrical complexity of prostate cancer
Decoding of human hand actions to handle missing limbs in Neuroprosthetics
Authors: Belić Jovana J. , Faisal Aldo A.
Published: February 2015

The only way we can interact with the world is through movements, and our primary interactions are via the hands, thus any loss of hand function has immediate impact on our quality of life. However, to date it has not been systematically assessed how coordination in the hand’s joints affects every day actions. This is important for two fundamental reasons. Firstly, to understand the representations and computations underlying motor control “in-the-wild” situations, and secondly to develop smarter controllers for prosthetic hands that have the same functionality as natural limbs. In this work we exploit the correlation structure of our hand and finger movements in daily-life. The novelty of our idea is that instead of averaging variability out, we take the view that the structure of variability may contain valuable information about the task being performed. We asked seven subjects to interact in 17 daily-life situations, and quantified behaviour in a principled manner using CyberGlove body sensor networks that, after accurate calibration, track all major joints of the hand. Our key findings are: 1. We confirmed that hand control in daily-life tasks is very low-dimensional, with four to five dimensions being sufficient to explain 80-90% of the variability in the natural movement data. 2. We established a universally applicable measure of manipulative complexity that allowed us to measure and compare limb movements across tasks. We used Bayesian latent variable models to model the low-dimensional structure of finger joint angles in natural actions. 3. This allowed us to build a naïve classifier that within the first 1000ms of action initiation (from a flat hand start configuration) predicted which of the 17 actions was going to be executed - enabling us to reliably predict the action intention from very short-time-scale initial data, further revealing the foreseeable nature of hand movements for control of neuroprosthetics and tele operation purposes. 4. Using the Expectation-Maximization algorithm on our latent variable model permitted us to reconstruct with high accuracy (<5°-6°MAE) the movement trajectory of missing fingers by simply tracking the remaining fingers. Overall, our results suggest the hypothesis that specific hand actions are orchestrated by the brain in such a way that in the natural tasks of daily-life there is sufficient redundancy and predictability to be directly exploitable for neuroprosthetics.
Vocation, motivation and approaches to learning: a comparative study
Authors: Arquero Jose Luis , Fernández-Polvillo Carmen , Hassall Trevor , Joyce John
Published: February 2015

Purpose

– The individual characteristics of students can have a strong influence on the success of the adopted innovations in terms of their transferability and sustainability. The purpose of this paper is to compare the motivations and approaches to learning on degrees with differing vocational components.

Design/methodology/approach

– Self-Determination Theory (SDT) and approaches to learning framework were used as theoretical background. Questionnaires were used to generate data. The sample was composed by 270 students enroled on differing degrees in term of motivation (accounting and nursing).

Findings

– The results reveal differences in the approaches to learning and motivation between nursing and accounting students. Nursing degree seem to attract more internally motivated students, presenting significantly higher scores in terms of deep approach and lower scores on surface approach. Significant relationships where found between motivation and approaches.

Research limitations/implications

– Data are obtained from students studying at a specific university in two degrees.

Practical implications

– The result suggest that different degrees could attract students with different motivations and approaches to learning. Educators must be aware of which type of students are being attracted to their classrooms, because the inconsistencies between the students’ motives and approaches, the way the contents are presented, the pedagogy and the assessment system could result in poorer learning and failure to transfer or sustain innovations.

Originality/value

– This paper adds to the very scarce literature linking motivation and approaches. The implications for curriculum design and delivery and specifically for assessment design are of interest for educators.
A decade of change in Australia’s DBA landscape
Authors: Wallace Michelle , Byrne Cathy , Vocino Andrea , Sloan Terry , Pervan Simon J. , Blackman Deborah
Published: February 2015

Purpose

– The purpose of this paper is to examine the dynamics of the Doctorate of Business Administration (DBA) in Australia through the lens of a changing higher education landscape. The paper reflects on issues raised in a previous analysis of DBA programmes undertaken a decade ago, and highlights persistent challenges and emerging opportunities for professional Doctorate programmes in the Australian context.

Design/methodology/approach

– Interviews were undertaken with higher degree research directors, deans of graduate schools, and DBA programme directors from all 18 Australian institutions offering the DBA in 2013. Quantitative data on enrolments, accreditation requirements, course structures; and demographics are contextualised within a qualitative view of programme purposes, student and institutional motivations, rationales and concerns. Particular focus is given to perceptions of the difference between traditional research doctorates (PhDs) and professional doctorates, especially the DBA.

Findings

– In the decade from 2003 to 2013 DBA enrolments are down but enquiries are up, indicating unmet demand. There is a shift in the players, with some smaller, regional universities dramatically increasing their enrolments, and larger, traditional institutions exiting the space altogether. Significant changes in accreditation criteria have generated a perceptual shift: where DBAs previously suffered from “academic snobbery” regarding their legitimacy, this perception is being challenged by standards which require DBA equivalence with a PhD. This shift in standards has also created some confusion amongst supervisors and candidates.

Originality/value

– There is limited research into the DBA award or its candidates, and academic literature is generally silent on DBA supervision. This piece of research, one of very few that specifically examine the DBA, reflects on the past decade, analyses the present context and identifies emerging issues for the delivery of DBA programmes in Australia.
Knowledge sharing and service innovativeness in offshore outsourced software development firms
Authors: Wickramasinghe Vathsala
Published: February 2015

Purpose

– The purpose of this study is to investigate the effects of knowledge sharing on innovativeness in offshore outsourced software development firms.

Design/methodology/approach

– For the study, a survey methodology was used, and 408 respondents attached to offshore outsourced software development firms in Sri Lanka responded. The hypothesized relationships were examined by structural equation modelling.

Findings

– The analysis yielded a two-component factor structure for knowledge sharing, which were termed as knowledge sharing practices and knowledge availability. It was found that both knowledge sharing practices and knowledge availability significantly positively predict innovativeness. The study provided empirical data to support the contention that organizations should be able to timely deliver knowledge to the right user to enhance innovativeness.

Practical implications

– The findings suggest the importance of creating an environment conducive for software developers to share information, insight, lessons learned and effective practices. Further, organizations have to establish a mechanisms to capture and capitalise knowledge residing in employees.

Originality/value

– In the knowledge-intensive offshore business sectors such as software development, economic value is found more in intangibles and less in tangibles. The sharing of knowledge leads to the dissemination of innovative ideas, which could improve work processes and develop new business opportunities. Therefore, it is important to conduct research that would lead to better understand drivers that enhance the innovativeness of service offerings of firms located in developing countries when competing internationally in offshore outsourced software development.
Intellectual Capital dynamics: seeing them “in practice” through a temporal lens
Authors: Giuliani Marco
Published: February 2015

Purpose

– The purpose of this study is to observe Intellectual Capital (IC) dynamics “in practice” through a temporal lens by considering IC as an on-going process, and thus taking into consideration its life cycle and how it changes over time.

Design/methodology/approach

– A longitudinal case study has been investigated by adopting a participant observation approach to understand how the dynamics of IC are understood in practice.

Findings

– This study spotlights three main conceptions of IC dynamics (value creation, IC activities and organizational change) which, although generally proposed in literature as separable concepts, do co-exist and interact, in practice as is reflected in the related managerial tools.

Research limitations/implications

– The main limitations of this study are twofold. The first is related to the methodology adopted and in particular, to the participant observation approach. The second is related to the specifics of the case study undertaken. This paper contributes to the literature on “Intellectual Capital in action” and “Intellectual Capital in practice” by enriching the understanding of IC dynamics.

Originality/value

– By comparison to the extant literature in which the IC dynamics concepts are considered separately, this study combines the three different concepts and examines themin vivo, adopting a longitudinal perspective.
Stepwise changes in viable but nonculturable Vibrio cholerae cells
Authors: Imamura Daisuke , Mizuno Tamaki , Miyoshi Shin‐ichi , Shinoda Sumio
Published: February 2015

Many bacterial species are known to become viable but nonculturable (VBNC) under conditions that are unsuitable for growth. In this study, the requirements for resuscitation of VBNC‐state Vibrio cholerae cells were found to change over time. Although VBNC cells could initially be converted to culturable by treatment with catalase or HT‐29 cell extract, they subsequently entered a state that was not convertible to culturable by these factors. However, fluorescence microscopy revealed the presence of live cells in this state, from which VBNC cells were resuscitated by co‐cultivation with HT‐29 human colon adenocarcinoma cells. Ultimately, all cells entered a state from which they could not be resuscitated, even by co‐cultivation with HT‐29. These characteristic changes in VBNC‐state cells were a common feature of strains in both V. cholerae O1 and O139 serogroups. Thus, the VBNC state of V. cholerae is not a single property but continues to change over time.
In Defence of British Politics Against the British Political Tradition
Authors: Richards David , Smith Martin J.
Published: February 2015

This article explores some of the current themes round the perceived crisis in British politics in supposed an age of ‘anti‐politics’. Drawing on Bernard Crick's In Defence of Politics, it offers a critique of what is referred to as a dominant British political tradition and in so doing seeks to challenge ‘demand‐side’ accounts that ostensibly defend the traditional arena politics of the Westminster system. Instead, it argues that developments around issues such as big data, social media and freedom of information have led to a more open society in recent years. It concludes by suggesting that if traditional political institutions wish to restore a greater degree of legitimacy, they need to ‘do’ or, more particularly, ‘supply’ politics differently, adapting to these changes by seeking out new modes of openness, engagement and accountability.
Stories of change in drug treatment: a narrative analysis of ‘whats’ and ‘hows’ in institutional storytelling
Authors: Andersen Ditte
Published: February 2015

Addiction research has demonstrated how recovering individuals need narratives that make sense of past drug use and enable constructions of future, non‐addict identities. However, there has not been much investigation into how these recovery narratives actually develop moment‐to‐moment in drug treatment. Building on the sociology of storytelling and ethnographic fieldwork conducted at two drug treatment institutions for young people in Denmark, this article argues that studying stories in the context of their telling brings forth novel insights. Through a narrative analysis of both ‘the whats’ (story content) and ‘the hows’ (storying process) the article presents four findings: (1) stories of change function locally as an institutional requirement; (2) professional drug treatment providers edit young people's storytelling through different techniques; (3) the narrative environment of the drug treatment institution shapes how particular stories make sense of the past, present and future; and (4) storytelling in drug treatment is an interactive achievement. A fine‐grained analysis illuminates in particular how some stories on gender and drug use are silenced, while others are encouraged. The demonstration of how local narrative environments shape stories contributes to the general understanding of interactive storytelling in encounters between professionals and clients in treatment settings.
Genetic Absence of nNOS Worsens Fetal Alcohol Effects in Mice. II: Microencephaly and Neuronal Losses
Authors: Karacay Bahri , Mahoney Jo , Plume Jeffrey , Bonthius Daniel J.
Published: February 2015

Background

Prenatal alcohol exposure can kill developing neurons, leading to microencephaly and mental retardation. However, not all fetuses are equally vulnerable to alcohol's neurotoxic effects. While some fetuses are severely affected and are ultimately diagnosed with fetal alcohol syndrome (FAS), others have no evidence of neuropathology and are behaviorally normal. These widely different outcomes among alcohol‐exposed fetuses are likely due, in part, to genetic differences. Some fetuses possess genotypes that make them much more vulnerable than others to alcohol's teratogenic effects. However, to date, only 1 gene has been identified whose mutation can worsen alcohol‐induced behavioral deficits in an animal model of FAS. That gene is neuronal nitric oxide synthase (nNOS). The purpose of this study was to determine whether mutation of nNOS can likewise worsen alcohol‐induced microencephaly and lead to permanent neuronal deficits.

Methods

Wild‐type and nNOS−/− mice received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days (PDs) 4 to 9. Beginning on PD 85, the mice underwent a series of behavioral tests; the results of which are reported in the companion paper. The brains were then weighed, and stereological cell counts were performed on the cerebral cortex and hippocampal formation, which are the brain regions that mediate the aforementioned behavioral tasks.

Results

Alcohol caused dose‐dependent microencephaly, but only in the nNOS−/− mice and not in wild‐type mice. Alcohol‐induced neuronal losses were more severe in the nNOS−/− mice than in the wild‐type mice in all of the brain regions examined, including the cerebral cortex, hippocampal CA3 subregion, hippocampal CA1 subregion, and dentate gyrus.

Conclusions

Targeted mutation of the nNOS gene increases the vulnerability of the developing brain to alcohol‐induced growth restriction and neuronal losses. This increased neuropathology is associated with worsened behavioral dysfunction. The results demonstrate the critical importance of genotype in determining the outcome of developmental alcohol exposure.
N‐Methyl‐d‐Aspartate Receptor Antagonism has Differential Effects on Alcohol Craving and Drinking in Heavy Drinkers
Authors: Krishnan‐Sarin Suchitra , O'Malley Stephanie S. , Franco Nicholas , Cavallo Dana A. , Morean Meghan , Shi Julia , Pittman Brian , Krystal John H.
Published: February 2015

Background

The objective of this study was to determine the effects of the N‐methyl‐d‐aspartate (NMDA) receptor antagonist, memantine (0, 20, 40 mg/d), upon alcohol drinking and craving in heavy drinkers with or without a family history (FH) of alcoholism, and to explore the modulatory influence of the presence of impulsivity on these outcomes.

Methods

Ninety‐two, nontreatment‐seeking, heavy drinkers received memantine or placebo for 8 days. On the eighth day, they received a priming dose of alcohol followed by a 3‐hour period of alcohol access.

Results

Memantine at a dose of 20 mg reduced alcohol craving but did not influence alcohol drinking. No effects of FH were observed. In participants with higher baseline levels of impulsivity, 40 mg of memantine reduced alcohol craving but increased alcohol drinking and alcohol‐induced stimulation.

Conclusions

NMDA receptor signaling may play divergent roles in mediating alcohol cue‐induced craving and alcohol drinking in heavy drinkers. The potential efficacy of memantine as monotherapy for alcohol use disorders may be limited by its tendency to disinhibit drinking in some individuals.
Gambling in Finland: problem gambling in the context of a national monopoly in the European Union
Authors: Tammi Tuukka , Castrén Sari , Lintonen Tomi
Published: February 2015

Aim

To describe and analyse the Finnish gambling market, regulatory system and the state of gambling research as well as the treatment system in operation for problem gamblers.

Method

A review of the literature and official documents relating to gambling in Finland, focusing primarily on the 1990s and 2000s.

Results

Only in recent years have gambling problems become a major issue for public debate in Finland. One reason for the increase in activity to address gambling problems is that, after Finland became a member of the European Union in 1995, the Finnish state gambling monopoly and its compatibility with European Union (EU) regulations have been questioned repeatedly. Since 2000, the Finnish government has put significant new resources into the research as well as the prevention and treatment of gambling problems. The resources grew from almost nothing to several million Euros in less than 10 years. This could be seen as an attempt to protect the national gambling monopoly system by showing that the Finnish monopoly system meets EU requirements.

Conclusions

Since joining the European Union in 1995, the Finnish government has been able to maintain its gambling monopoly by providing substantial resources to signal a commitment to minimizing problem gambling.
GOVERNANCE MECHANISMS, SOCIAL PERFORMANCE DISCLOSURE AND PERFORMANCE IN MICROFINANCE: DOES LEGAL STATUS MATTER?
Authors: ESTAPÉ‐DUBREUIL Glòria , TORREGUITART‐MIRADA Consol
Published: February 2015

In this paper we examine diverse governance mechanisms implemented by microfinance institutions, as well as their relationships with both social and financial performance, using a database obtained from the MIX, consisting of MFIs reporting data both on financial and social performance. We find that some governance mechanisms are significantly different among MFIs depending on their legal status. MFIs with NGO status have more diversity in their boards, adhere more to fair practices related to their human resources, and pay more attention to training in social performance management. Furthermore, we find that NGOs perform better at a social level (serve more clients; reach more poor clients; a large fraction of their borrowers are women). We find that external governance mechanisms have little or no effect, while board characteristics consistently and significantly affect social performance.
Annexin A1 mimetic peptide controls the inflammatory and fibrotic effects of silica particles in mice
Authors: Trentin P G , Ferreira T P T , Arantes A C S , Ciambarella B T , Cordeiro R S B , Flower R J , Perretti M , Martins M A , Silva P M R
Published: February 2015

Background and Purpose

Endogenous glucocorticoids are pro‐resolving mediators, an example of which is the endogenous glucocorticoid‐regulated protein annexin A1 (ANXA1). Because silicosis is an occupational lung disease characterized by unabated inflammation and fibrosis, in this study we tested the therapeutic properties of the N‐terminal ANXA1‐derived peptide annexin 1‐(2‐26) (Ac2‐26) on experimental silicosis.

Experimental Approach

Swiss‐Webster mice were administered silica particles intranasally and were subsequently treated with intranasal peptide Ac2‐26 (200 μg per mouse) or dexamethasone (25 μg per mouse) for 7 days, starting 6 h post‐challenge. Ac2‐26 abolished the leukocyte infiltration, collagen deposition, granuloma formation and generation of pro‐inflammatory cytokines evoked by silica; these variables were only partially inhibited by dexamethasone.

Key Results

A clear exacerbation of the silica‐induced pathological changes was observed in ANXA1 knockout mice as compared with their wild‐type (WT) littermate controls. Incubation of lung fibroblasts from WT mice with Ac2‐26 in vitro reduced IL‐13 or TGF‐β‐induced production of CCL2 (MCP‐1) and collagen, but this peptide did not affect the production of CCL2 (MCP‐1) by stimulated fibroblasts from formyl peptide receptor type 1 (FPR1) knockout mice. Ac2‐26 also inhibited the production of CCL2 (MCP‐1) from fibroblasts of FPR2 knockout mice.

Conclusions and Implications

Collectively, our findings reveal novel protective properties of the ANXA1 derived peptide Ac2‐26 on the inflammatory and fibrotic responses induced by silica, and suggest that ANXA1 mimetic agents might be a promising strategy as innovative anti‐fibrotic approaches for the treatment of silicosis.
Immunotherapy based on bispecific T‐cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma
Authors: Zou Jianxuan , Chen Dan , Zong Yunhui , Ye Sisi , Tang Jinle , Meng Huimin , An Gangli , Zhang Xingding , Yang Lin
Published: February 2015

Bispecific antibodies play an important role in immunotherapy. They have received intense interest from pharmaceutical enterprises. The first antibody drug, OKT3 (muromonab‐CD3), showed great performance in clinical treatment. We have successfully developed a single‐chain variable fragment (ScFv) combination of anti‐CD3 ScFv and anti‐CD138 ScFv with the hIgG1 Fc (hIgFc) sequence. The novel bispecific T‐cell engager (BiTE) with an additional hIgFc (BiTE‐hIgFc, STL001) can target T cells, natural killer cells, and multiple myeloma cells (RPMI‐8226 or U266). In addition, BiTE‐hIgFc (STL001) has nanomolar‐level affinity to recombinant human CD138 protein and shows more potent antitumor activity against RPMI‐8226 cells than that of separate aCD3‐ScFv‐hIgFc and aCD138‐ScFv‐hIgFc, or the isotype mAb in vitro or in vivo.
Economic evaluations of contingency management in illicit drug misuse programmes: A systematic review
Authors: Shearer James , Tie Hiong , Byford Sarah
Published: February 2015

Issues

UK clinical guidelines published in 2007 recommended contingency management (CM) as an adjunct to opiate substitution therapy. However, CM has not been adopted in the UK despite evidence of clinical effectiveness. Evidence for the cost‐effectiveness of CM is less clear and will need to be explored if CM is to be adopted by national health systems in countries such as the UK.

Approach

Systematic review and descriptive synthesis of published economic evaluations.

Key Findings

The review identified nine published studies that could be classified as economic evaluations. These were all based within US treatment settings, and five were conducted by the same group of authors. All studies found that the addition of CM to usual care increased both costs and effects (commonly drug abstinence or medication adherence).

Implications

This review confirms that the existing evidence base for cost‐effectiveness has limited generalisability beyond the original research clinical settings and populations.

Conclusion

The data were not sufficiently strong to make any conclusion about the cost‐effectiveness of CM. More relevant and comprehensive evidence for cost‐effectiveness than currently exists is needed. [Shearer J, Tie H, Byford S. Economic evaluations of contingency management in illicit drug misuse programmes: A systematic review. Drug Alcohol Rev 2015]
Think fast! The relationship between goal prediction speed and social competence in infants
Authors: Krogh‐Jespersen Sheila , Liberman Zoe , Woodward Amanda L.
Published: February 2015

Skilled social interactions require knowledge about others' intentions and the ability to implement this knowledge in real‐time to generate appropriate responses to one's partner. Young infants demonstrate an understanding of other people's intentions (e.g. Woodward, Sommerville, Gerson, Henderson & Buresh, 2009), yet it is not until the second year that infants seem to master the real‐time implementation of their knowledge during social interactions (e.g. Warneken & Tomasello, 2007). The current study investigates the possibility that developments in social competence during the second year are related to increases in the speed with which infants can employ their understanding of others' intentions. Twenty‐ to 22‐month‐old infants (N = 23) viewed videos of goal‐directed actions on a Tobii eye‐tracker and then engaged in an interactive perspective‐taking task. Infants who quickly and accurately anticipated another person's future behavior in the eye‐tracking task were more successful at taking their partner's perspective in the social interaction. Success on the perspective‐taking task was specifically related to the ability to correctly predict another person's intentions. These findings highlight the importance of not only being a ‘smart’ social partner but also a ‘fast’ social thinker.
Vowel bias in Danish word‐learning: processing biases are language‐specific
Authors: Højen Anders , Nazzi Thierry
Published: February 2015

The present study explored whether the phonological bias favoring consonants found in French‐learning infants and children when learning new words (Havy & Nazzi, 2009; Nazzi, 2005) is language‐general, as proposed by Nespor, Peña and Mehler (2003), or varies across languages, perhaps as a function of the phonological or lexical properties of the language in acquisition. To do so, we used the interactive word‐learning task set up by Havy and Nazzi (2009), teaching Danish‐learning 20‐month‐olds pairs of phonetically similar words that contrasted either on one of their consonants or one of their vowels, by either one or two phonological features. Danish was chosen because it has more vowels than consonants, and is characterized by extensive consonant lenition. Both phenomena could disfavor a consonant bias. Evidence of word‐learning was found only for vocalic information, irrespective of whether one or two phonological features were changed. The implication of these findings is that the phonological biases found in early lexical processing are not language‐general but develop during language acquisition, depending on the phonological or lexical properties of the native language.
Diversification and biodiversity dynamics of hot and cold spots
Authors: Melián Carlos J. , Seehausen Ole , Eguíluz Víctor M. , Fortuna Miguel A. , Deiner Kristy
Published: February 2015

The determinants that shape the distribution of diversity of life on Earth have been long discussed and many mechanisms underlying its formation have been proposed. Yet connecting the biogeography of hot and cold spots of diversiﬁcation and current biodiversity patterns to the microevolutionary processes remains largely unexplored. Here, we combine a landscape genetics model based on demographic stochasticity with a speciation model that can be interpreted as a model of the evolution of premating incompatibility or assortative mating to map diversiﬁcation rates in a spatial context. We show that landscape structure and the intensity and directionality of gene ﬂow strongly inﬂuence the formation of hot and cold spots and its connection to patterns in species richness. Speciﬁcally, hot and cold spots form in landscapes in which gene ﬂow is suﬃciently strongly structured that the metacommunity nearly breaks up into several disconnected metacommunities. In such a landscape structure, speciation hot spots originate in the center or in the periphery of the landscape depending on whether the direction of gene ﬂow is from the periphery to the center or viceversa, respectively. However, for any given level of gene ﬂow intensity, diversiﬁcation rates are approximately twice higher in the center than in the periphery of the landscape. These results suggest that sinks may form diversiﬁcation hot spots with higher probability than sources, in particular, those sinks surrounded by highly diversiﬁed sources in diﬀerent locations of the landscape. Joining mechanistically microevolutionary and macroevolutionary processes on landscapes present many fascinating challenges and opportunities to connect the biogeography of diversiﬁcation with biodiversity dynamics.
Influence of plant growth and root architecture of Italian ryegrass (Lolium multiflorum) and tall fescue (Festuca arundinacea) on N recovery during winter
Authors: Malcolm B. J. , Moir J. L. , Cameron K. C. , Di H. J. , Edwards G. R.
Published: February 2015

Nitrate () leaching is an environmental and health concern. In grazed pasture systems, leaching primarily occurs beneath animal urine patch areas due to high nitrogen (N) loading and the inability of pasture plants to capture all of this N. This study investigated the relative importance of plant growth and root architecture to recover soil N. Herbage N recovery, dry matter (DM) yield and root architecture, following injections of 15N‐enriched urea at different soil depths (5, 25 and 45 cm), were measured for Italian ryegrass (Lolium multiflorum Lam.) and tall fescue (Festuca arundinacea Schreb.) grown in soil monolith lysimeters (18 cm diameter × 70 cm depth) under simulated South Island, New Zealand winter temperature and light levels. Total herbage N uptake and DM yield were on average 24 and 48% greater in L. multiflorum than F. arundinacea respectively. Root length density (cm cm−3 soil) in the 5‐ to 25‐cm‐depth horizon was similar between species. In the 25‐ to 45‐cm‐depth horizon, F. arundinacea roots were found at higher densities than L. multiflorum. In the 45‐ to 65‐cm‐depth horizon, root length density was fourfold to ninefold higher for F. arundinacea than L. multiflorum, but N uptake efficiency was greater in L. multiflorum (0·48 mg 15N m−1 root) than F. arundinacea (0·09 mg 15N m−1 root). The results suggest that deep F. arundinacea roots are relatively inactive during the winter period and confirm that plant growth is more important than root architecture (e.g. deep roots) to recover soil N and ultimately reduce nitrate leaching losses.
Intrafamilial, Preferentially Mother‐to‐Child and Intraspousal, Helicobacter pylori Infection in Japan Determined by Mutilocus Sequence Typing and Random Amplified Polymorphic DNA Fingerprinting
Authors: Yokota Shin‐ichi , Konno Mutsuko , Fujiwara Shin‐ichi , Toita Nariaki , Takahashi Michiko , Yamamoto Soh , Ogasawara Noriko , Shiraishi Tsukasa
Published: February 2015

Background

The infection route of Helicobacter pylori has been recognized to be mainly intrafamilial, preferentially mother‐to‐child, especially in developed countries. To determine the transmission route, we examined whether multilocus sequence typing (MLST) was useful for analysis of intrafamilial infection. The possibility of intraspousal infection was also evaluated.

Materials and Methods

Clonal relationships between strains derived from 35 index Japanese pediatric patients, and their family members were analyzed by two genetic typing procedures, MLST and random amplified polymorphic DNA (RAPD) fingerprinting.

Results

Mostly coincident results were obtained by MLST and RAPD. By MLST, the allele of loci in the isolates mostly matched between the index child and both the father and mother for 9 (25.7%) of the 35 patients, between the index child and the mother for 25 (60.0%) of the 35 patients.

Conclusions

MLST is useful for analyzing the infection route of H. pylori as a highly reproducible method. Intrafamilial, especially mother‐to‐children and sibling, infection is the dominant transmission route. Intraspousal infection is also thought to occur in about a quarter in the Japanese families.
Behaviour of four different B16 murine melanoma cell sublines: C57BL/6J skin
Authors: Danciu Corina , Oprean Camelia , Coricovac Dorina E. , Andreea Cioca , Cimpean Anca , Radeke Heinfried , Soica Codruta , Dehelean Cristina
Published: February 2015

Transplantable murine melanomas are well‐established models for the study of experimental cancer therapies. The aim of this study was to explore the behaviour of four different B16 murine melanoma cell sublines after inoculation into C57BL/6J mice; and, more specifically to analyse skin changes, with respect to two specific parameters: clinical (tumour volume, melanin amount, erythema) and histological (H & E, S100, VEGF expression). Both non‐invasive and invasive analysis showed that B164A5 is the most aggressive melanoma cell line for C57BL/6J's skin, followed by B16F10 and then by diminished aggressive growth pattern by the B16GMCSF and B16FLT3 cell lines.
CYP3A isoforms in Ewing's sarcoma tumours: an immunohistochemical study with clinical correlation
Authors: Zia Hamid , Murray Graeme I. , Vyhlidal Carrie A. , Leeder J. Steven , Anwar Ahmed E. , Bui Marilyn M. , Ahmed Atif A.
Published: February 2015

Ewing's sarcoma is an aggressive malignancy of bone and soft tissue with high incidence of metastasis and resistance to chemotherapy. Cytochrome P450 (CYP) monooxygenases are a family of enzymes that are involved in the metabolism of exogenous and endogenous compounds, including anti‐cancer drugs, and have been implicated in the aggressive behaviour of various malignancies. Tumour samples and clinical information including age, sex, tumour site, tumour size, clinical stage and survival were collected from 36 adult and paediatric patients with Ewing's sarcoma family tumours. Tissue microarrays slides were processed for immunohistochemical labelling for CYP3A4, CYP3A5 and CYP3A7 using liver sections as positive control. The intensity of staining was scored as negative, low or high expression and was analysed statistically for any association with patients' clinical information. Four cases were later excluded due to inadequate viable tissue. CYP3A4 staining was present in 26 (81%) cases with high expression noted in 13 (40%) of 32 cases. High expression was significantly associated with distant metastases (P < 0.05). CYP3A5 and CYP3A7 were expressed in 5 and 13 cases respectively (15.6%, 40.6%). There was no association between the expression of CYP3A isoforms and age, sex, tumour size, or location (pelvic or extra‐pelvic). None of the biomarkers showed any correlation with overall or disease‐free survival. In conclusion, expression of CYP3A isoforms is noted in Ewing's sarcoma tumours and high CYP3A4 expression may be associated with metastasis. Additional studies are needed to further investigate the role of CYP3A4 in the prognosis of these tumours.
Saudi Arabian adult intensive care unit pressure ulcer incidence and risk factors: a prospective cohort study
Authors: Tayyib Nahla , Coyer Fiona , Lewis Peter
Published: February 2015

The purpose of this study was to identify pressure ulcer (PU) incidence and risk factors that are associated with PU development in patients in two adult intensive care units (ICU) in Saudi Arabia. A prospective cohort study design was used. A total of 84 participants were screened second daily basis until discharge or death, over a consecutive 30‐day period, out of which 33 participants with new PUs were identified giving a cumulative hospital‐acquired PU incidence of 39·3% (33/84 participants). The incidence of medical devices‐related PUs was 8·3% (7/84). Age, length of stay in the ICU, history of cardiovascular disease and kidney disease, infrequent repositioning, time of operation, emergency admission, mechanical ventilation and lower Braden Scale scores independently predicted the development of a PU. According to binary logistic regression analyses, age, longer stay in ICU and infrequent repositioning were significant predictors of all stages of PUs, while the length of stay in the ICU and infrequent repositioning were associated with the development of stages II–IV PUs. In conclusion, PU incidence rate was higher than that reported in other international studies. This indicates that urgent attention is required for PU prevention strategies in this setting.
Zosteriform pemphigoid after zoster: Wolf's isotopic response
Authors: Gurel Mehmet S , Savas Sevil , Bilgin Fusun , Erdil Duygu , Leblebici Cem , Sarikaya Ebru
Published: February 2015

The Wolf isotopic response describes the occurrence of a new, unrelated disease that appears at the same location as a previously healed disease. The most common primary skin disorder of this phenomenon is herpes zoster and less frequently, herpes simplex. We report a case of 79‐year‐old woman who have bullous pemphigoid (BP) with dermatomal distribution that developed at the site of previously healed herpes zoster. Based on clinical, histological and immunofluorescence findings, the patient was diagnosed with localized BP in a site of prior herpes zoster. BP developing at the site of healed herpes zoster is the first reported case. Recognition of this phenomenon is important for correct clinicopathologic diagnosis and may improve our understanding of the underlying pathophysiologic processes.
Judah Benjamin: Marginalized Outsider or Admitted Insider?
Authors: MacMillan Catharine
Published: February 2015

Judah Benjamin (1811–1884) was one of the greatest of nineteenth‐century lawyers. This article analyses how a young man who might have been marginalized in society because of the circumstances of his birth, ethnic origin, and religious identity rose to prominence in law, politics, and business in the United Kingdom and the United States.
Pairwise versus presence–absence approaches for analysing biodiversity patterns
Authors: Soberón Jorge
Published: February 2015

It has been proposed that the study of co‐occurrence of species, which is traditionally performed using full presence–absence matrices of sets of many species, could benefit from simply testing for random co‐occurrence between pairs of species, and that use of a full presence–absence matrix is tantamount to regarding it as having some real ecological identity. Here I argue that although there are valid questions that can be answered using a pairwise approach, there are many others that naturally require the analysis of entire sets of species in a joint way, as provided for through the use of full presence–absence matrices. Moreover, there are theoretical and mathematical advantages to the use of presence–absence matrices, a few of which are briefly discussed in this short note.
Association Between Pulse Wave Velocity and a Marker of Renal Tubular Damage (N‐Acetyl‐β‐D‐Glucosaminidase) in Patients Without Diabetes
Authors: Ouchi Motoshi , Oba Kenzo , Saigusa Taro , Watanabe Kentaro , Ohara Makoto , Matsumura Noriaki , Suzuki Tatsuya , Anzai Naohiko , Tsuruoka Shuichi , Yasutake Masahiro
Published: February 2015

The authors assessed the association between the ratio of urinary activity of N‐acetyl‐β‐D‐glucosaminidase (NAG) to creatinine and the brachial‐ankle pulse wave velocity (baPWV) in patients without overt diabetes mellitus (DM). This was a cross‐sectional study of 233 patients who had an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and no history of kidney disease. Patients were divided into two groups: high NAG group (>5.8 U/g creatinine) and low NAG group (≤5.8 U/g creatinine). Mean baPWVs of the high NAG group were significantly higher than those of the low NAG group in both the eGFR ≥30 and <60 tertiles and the eGFR ≥60 and <90 tertiles. The baPWV was positively correlated with NAG in all patients (r=0.341, P<.001). Stepwise multivariate regression analysis showed that the baPWV was significantly related with NAG, age, and systolic blood pressure. Elevated NAG is related to elevated arterial stiffness in patients without DM.
Adalimumab in the treatment of moderate‐to‐severe chronic plaque psoriasis in patients switching from other biologics
Authors: Sator P. , Richter L. , Saxinger W. , Vasiljevic M. , Stingl G.
Published: February 2015

Background

Ample evidence shows that switching from one biological agent to another may prove effective when response to the first one is inadequate. Nevertheless, there are little data so far showing the efficacy and safety of adalimumab in patients with plaque psoriasis who previously received another biologic agent.

Objective

We evaluated the 1‐year effectiveness, safety and quality‐of‐life outcomes patients with psoriasis who had switched to adalimumab from other biologic therapies.

Methods

Forty‐two patients who participated in this Austrian multicenter study were treated with adalimumab over a 1‐year period, after switching from efalizumab, infliximab or etanercept.

Effectiveness was assessed using standardized tools for measurement of disease severity [Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI)] and quality of life [Dermatology Life Quality Index (DLQI)]. The study endpoints were evaluated using the all‐treated population.

Results

The mean percentage of improvement at the end of the study was 74.3% for PASI, 81.6% for DLQI and 83.6% for NAPSI, demonstrating a considerable benefit of treatment with adalimumab. The safety profile observed was consistent with previous clinical trials for adalimumab, and no new safety signals were observed.

Conclusion

Adalimumab therapy in patients with plaque psoriasis previously treated with other biologic agents demonstrates effectiveness, safety and improvement in quality of life.
The effect of marjoram (Origanum majorana) tea on the hormonal profile of women with polycystic ovary syndrome: a randomised controlled pilot study
Authors: Haj‐Husein I. , Tukan S. , Alkazaleh F.
Published: February 2015

Background

In traditional medicine, marjoram herb (Origanum majorana) is locally reputed for its ability to restore hormonal balance and to regulate the menstrual cycle. Therefore, this pilot study aimed to investigate the effects of marjoram tea on the hormonal profile of women with polycystic ovary syndrome (PCOS) in a randomised, double‐blind, placebo‐controlled trial.

Methods

Twenty‐five patients were assigned to receive marjoram tea or a placebo tea twice daily for 1 month (intervention group: n = 14; placebo group: n = 11). The hormonal and metabolic parameters measured at baseline, as well as after the intervention, were: follicle‐stimulating hormone, luteinising hormone, progesterone, oestradiol, total testosterone, dehydroepiandrosterone‐sulphate (DHEA‐S), fasting insulin and glucose, homeostasis model assessment for insulin resistance (HOMA‐IR) and glucose to insulin ratio.

Results

Marjoram tea significantly reduced DHEA‐S and fasting insulin levels (P < 0.05) by a mean (SD) of 1.4 (0.5) μmol L−1 and 1.9 (0.8) μU mL−1, respectively. In comparison to the placebo group, the change was only significant for DHEA‐S (P = 0.05) but not for insulin (P = 0.08). HOMA‐IR was not reduced significantly in the intervention group (P = 0.06), although the change was significant compared to the placebo group (P < 0.05).

Conclusions

The results obtained in the present study show the beneficial effects of marjoram tea on the hormonal profile of PCOS women because it was found to improve insulin sensitivity and reduce the levels of adrenal androgens. Further research is needed to confirm these results and to investigate the active components and mechanisms contributing to such potential beneficial effects of marjoram herb.