bluuebunny/crossref_metadata_2025 huggingface dataset:
Data Sharing for Sustainable Building Assessment
Authors: Biswas Tajin , Krishnamurti Ramesh
Published: December 2012

Sustainable design assessment requires information, which is aggregated from different phases of a building design, and evaluated according to criteria specified in a ‘sustainable building rating system.’ In the architecture engineering and construction (AEC) domain much of the necessary information is available through open source data standards such as Industry Foundation Classes (IFC). However, no single standard that provides support for sustainability assessment completely suffices as a data structure. This paper explores the augmentation of the Construction Operations Building information exchange (COBie) model, as an intermediary data structure, to bridge between requirements of the Leadership in Energy and Environmental Design (LEED) rating system and a building information model. Development of a general framework for data sharing and information management for LEED assessments is illustrated through an implementation of a prototype using functional databases. The prototype checks and augments available data as needed, which is used to populate LEED submission templates.
Design-Built Rationalization Strategies and Applications
Authors: Dritsas Stylianos
Published: December 2012

Rationalisation of architectural design is paramount to manufacturing and its construction. This paper presents a methodology of rationalisation of building envelope geometry. We discuss methods for understanding and addressing design complexity; review two theoretical models of rationalisation: the pre-rational and post-rational design principles; illustrate their benefits and limitations and demonstrate their meeting point proposing an integrated performance-oriented model for analysis and design of building envelopes, using digital design techniques.
Ornamental Discretisation of Free-form Surfaces
Authors: Manahl Markus , Stavric Milena , Wiltsche Albert
Published: December 2012

The adoption of digital planning methods has given rise to an unprecedented formal freedom in architectural design. Free-form shapes enjoy considerable popularity in architectural production today. However, these shapes prove to be notoriously hard to fabricate. In the course of a funded research project we investigated the approximation of continuous double-curved surfaces by discrete meshes consisting solely of planar facets, which can be fabricated efficiently using standardised, mass-produced building materials. We introduce our geometrical approach, which is based on the intersection of tangent planes to the surface, and present the digital tools we conceived to integrate the processes of design rationalisation and form-finding.
Computational Design of a Bio Inspired Responsive Architectural Façade System
Authors: Dutt Florina , Das Subhajit
Published: December 2012

This research intends to illustrate a nonlinear relationship that could be drawn between the fundamental processes in living systems and architectural design of responsive surface. The research focuses on deriving a set of parametric relationships from the phenomenon in cell biology and generating an architectural expression of a responsive façade system. The research methods primarily investigates the cell – to – cell connection in mammary epithelial cell system and review the evident relay of communication across the entire system of cells. This thorough investigation unfolds the logical parameters of the biological system that delineates the dynamic feedback mechanism and changes in the cell surface conditions initiated from the changes in the extracellular environment (ECM). The research findings of this complex mechanism are further translated though parametric modeling tool (in this case Generative Components) to model the causalities of the changes in cell environment and surface condition changes. In the next phase of our research we have explored the architectural utility of this hybridized model operating in a user defined controlled environ, and not just a mere response to biological stimulus.
The long-term future of dentistry
Authors: Howe Earl
Published: December 2012

Dentistry in the National Health Service (NHS) is undergoing some of the most significant changes in its history as the pilot programme continues to shape the dental contract of the future. Lord Howe, Health Minister, has been at the helm of the transformation since taking responsibility for oral health and dentistry policy when the coalition government formed in 2010. Now, two years into an extraordinary journey, he gives his insight into the progress and hopes for the long-term future of dentistry.
Dental contract reform: opportunities and challenges
Authors: Gregory Sue
Published: December 2012

Embarking on dental contract reform is not without its risks. The current piloting for reform of the National Health Service (NHS) contract is testing a number of elements to contribute towards the development of a very different way of delivering NHS dental services, the core of which would be capitation, quality and outcomes, and a clinical care pathway approach. Early learning from the first year of piloting confirms a high level of satisfaction from both patients and practice staff with the care pathway approach, especially its emphasis on prevention. Nevertheless, significant challenges remain in designing the detail of a contract that will deliver the required outcomes for patients, service commissioners and the dental team.
Why should the NHS continue to fund orthodontic treatment in the current financial climate?
Authors: Hunt Nigel
Published: December 2012

The commissioning of future dental services is once again in the spotlight as we move into the transition phase before the full effect of the commissioning boards comes in April 2013. The delivery of specialist orthodontic care has been particularly badly disrupted over the past 18 months with gross variations in the way in which procurement exercises have been undertaken by some primary care trusts. As a consequence, the British Orthodontic Society (BOS) has received complaints from both patients and specialists focusing on the disruption to the delivery of services and continuity of patient care.
The future of continuing professional development
Authors: Herbert Claire
Published: December 2012

Head of Revalidation at the General Dental Council (GDC), Claire Herbert guides us through the regulator’s ongoing review of its current continuing professional development (CPD) requirements.
How to avoid litigation
Authors: Tiernan John
Published: December 2012

There are many myths about litigation. This is not surprising since it is one of the most frightening and distracting experiences that a dental professional can encounter. This article seeks to illustrate why litigation might occur, and recommends some strategies to protect yourself and, equally important, position yourself effectively to defend a situation where such litigation is unjustified.
Re-establishing the primacy of the basic sciences in undergraduate dental education
Authors: Mahadevan Vishy
Published: December 2012

Frequent and, at times, drastic curricular changes in undergraduate dental education in the UK during the past 15 or so years have posed considerable challenges to those involved in the planning, organisation and delivery of effective teaching programmes within the ambit of the curriculum. Nowhere is this more true and, indeed, more critical than in the provision of instruction in the basic sciences: anatomy, physiology, biochemistry, pathology and microbiology, oral biology and pharmacotherapeutics. At the outset you may be tempted to ask: why must the curriculum change at all?
Pension reforms
Authors: Blakeman Mark
Published: December 2012

Dentists working in the NHS will be well aware that there are a number of changes taking place in the public sector pension scheme. Mark Blakeman, National Sales Manager at Wesleyan Medical Sickness, looks at how changes to the National Health Service (NHS) pension scheme are affecting the profession and provides an update and look ahead to what happens next.
‘You cannot be serious!’: McEnroe’s Ghost causes a scene at the Wimbledon Lawn Tennis Museum
Authors: Chittenden Tara
Published: December 2012

Exhibition designers are now encountering unprecedented opportunities to merge the virtual and the real in the creation of scenes. I argue that there is a clear need to examine how the 'technospectacle' is transforming the visual and material regimes of scene design in a museum context.
Bringing together the technique of Pepper's Ghost with new projection and filming technology, the Wimbledon Lawn Tennis Museum introduces a 3D life-sized ghost of John McEnroe into a reconstruction of the 1980s Dressing Room. In this article I investigate the intersection of technology and
tangible reconstruction in 'McEnroe's Ghost'. In my analysis I question not only how different arrangements of time and space constitute the scene as encountered by visitors but how these arrangements serve to create a real sense of presence in the experience of viewing the virtual body. I
conclude that such technologically augmented scenes suggest rich possibilities to extend scene design visually, conceptually and dramatically, via new intersections of projection and performance.
Siobhan Davies RePlay: corporeality and materiality in the online environment
Authors: Whatley Sarah
Published: December 2012

This article discusses the digital dance archive Siobhan Davies RePlay to explore how the dancer's making and performance process translates to an online environment, to ask what is lost and what is gained? It will consider how the digital environment captures and transmits the material
form of the 'object' and how RePlay seeks to convey something of the mutable nature of dance rather than a static, unchanging digital resource. The article will focus particularly on one aspect of RePlay, which more that any other part of the archive reveals the process of design and its role
in conveying the artistic vision of the choreographer (Siobhan Davies) and the whole creative team involved in the archive development. These 'kitchens' are designed to provide users with a different experience of two dance works: Bird Song (2004) and In Plain Clothes (2006). Named 'kitchens'
as a reference to a process involved in the construction of a dance work that is analogous to 'cooking', the kitchens were designed to enable the user to 'peel back' the many layers within the creative process of making and performing a dance. These two very different digital objects are designed
to offer a visual way of comprehending the structure of the dance; the relationship between dance, sound, costume design and scenography; and to offer access to the dancer's own observations and reflections on their making process. Score-like in form, they also can be reactivated or reconstructed
by the user, in physical or virtual space. But ultimately each exists as an aesthetic object in its own right, whilst offering a novel approach to distributing dance and the knowledge that is embodied within the dance.
REVIEWS
Authors: Kuksa Iryna , Kuksa Iryna
Published: December 2012

ARTWORK AS SOCIAL MODEL: A MANUAL OF QUESTIONS AND PROPOSITIONS, STEPHEN WILLATS, (2012) Sheffield: RGAP, 336 pp., ISBN 978–0–9569024–2–9 (hbk), £18

AN INTRODUCTION TO THEATRE DESIGN, STEPHEN DI BENEDETTO, (2012) Oxford: Routledge, 222 pp., ISBN 978–0–415–54754–3
(pbk), £26.39
A cross-medial approach to communicate a work of art: the Sala Bologna within the ‘Apa the Etruscan’ project
Authors: Luca Daniele De , Guidazzoli Antonella , Liguori Maria Chiara , Spigarolo Micaela
Published: December 2012

Inside the Museum of the History of Bologna the same work of art, the Sala Bologna, realized in 1575 at the Vatican Apostolic Palace and reproducing a bird’s-eye view of Bologna at the time, is offered to the public in three different ways: as a facsimile fresco set in the entrance
hall and as two different digital outputs – a set for the 3D cartoon Apa the Etruscan and 2700 Years of Bologna History, currently shown in the immersive room especially designed by Cineca for the museum, and for an immersive and interactive navigation through a head-tracking 3D visor.
This article focuses upon the experience of modelling a philologically accurate three-dimensional scenario (the Sala Bologna) for a short edutainment movie and other subsequent outputs. Apa the Etruscan, a joint production by Cineca and Genus Bononiae, is the first 3D stereoscopic Blender-made
movie with high historical standards applied to an entire city with four different geo-referenced scenarios and seven historical periods: Etruscan, Roman, Medieval, Renaissance, seventeenth century, eighteenth century and present day. The methodology developed for this inter-disciplinary realization
used only open-source tools, except for the City Engine adopted in the procedural modelling. The aim of the movie is to take advantage of computer-based visualization methods to deliver information (culture) minimizing cognitive overload. The choice of open-source software made the production
pipeline a case study, highlighting interesting features such as model reusability that, for the Sala Bologna as well as for other digital assets developed for the movie, has already fostered the implementation of new applications. The modelling of the Sala Bologna is proposed as a significant
example of the twofold challenge dealt within the production pipeline: including philological constraints inside a traditional 3D movie pipeline production and test in a cross-media framework of models tagged with metadata for both communication and research activities.
Recreating The Flying Dutchman: rediscovering the lost art of the effects projector
Authors: Guy Shane
Published: December 2012

Before the massed ranks of data projectors, LED screens, pixel mapping and video servers found their way into the theatre there was already the need for the spectacular moving image. In ancient times these effects were provided by shadow puppets and in the fifteenth century the magic
lantern was developed; by the nineteenth century the sophistication of the latter was such that it could be used in theatrical performances. Thus the theatrical effects projector was born.

The most elaborate use of effects projectors was for The Ring Cycle (Bentham 1957) and for the 1957
production of The Flying Dutchman at the old Sadler’s Wells Theatre. This article explores how the effects projector was used in the original The Flying Dutchman, and charts how these effects can be recreated.
Motion capture and performance
Authors: Gomide João Victor Boechat
Published: December 2012

The production of digital animation by means of motion capture from live, real-time performance of actors, athletes or any human being has become more and more popular. On the one hand there are film productions and the digital game industry, which drive technology improvements and
is consumed by hundreds of millions of people. On the other hand, there is the user mass, made mostly of potential users, which require more compact and cheaper solutions for their productions.

The process of animating characters by means of this technique introduces taxonomy discussions
that, after all, are useful for differentiating the two groups. The digital motion capture appeared in the late 1980s. Until the beginning of the twenty-first century, only body movements were captured while facial expressions were manually animated. This is due to the subtlety of facial
movements and the consequent need for better accuracy in mapping the dozens of muscle groups and their links. When this facial technique was made possible, it was then named performance capture. Independently of the name given to the technique, the new possibilities of creation, production
and improved performance are wide.

This article approaches these aspects from the point of view of the evolution of audio-visual production since the appearance of animation, while the process of motion capture is presented with its impact on animation and performance. The expectations
about the use of the technique are discussed with the equipment available. The open source code software for motion capture, OpenMoCap, is presented here as an alternative for the current production scenario.
Travels in augmented reality
Authors: Goto John , Leach Matthew
Published: December 2012

This article describes several artistic projects using the medium of augmented reality and gives a technical outline of how it works and its developing nature.

Some of the works were completely original, created specifically with the available functionality of augmented reality in
mind. Others were adaptations of previous artworks, creating new challenges and opportunities in the change of medium.

Digital content permeates through the modern world, but the use of augmented–reality technologies allows meaningful connections to be made between digital content
and real-world locations. Simulated artefacts can be embedded within real-world space, creating a live montage. Similar examples, of a less technological nature, can be found throughout modern history - variously described as tricks to fool observers or tools to enhance artistry, from apparitions
in stage productions to mainstays of early cinema. A fundamental theme explored in this article is the artistic status of augmented reality. Is it a transitory fad, or an emerging platform? Does it matter which?

The artworks described vary from being placed at specific locations in public
areas, being detached from place and available everywhere, to incorporation in traditional and non-traditional gallery spaces. Spectres of jazz migrants reinhabited venues that were meaningful in their lives, and an invisible artist offered a cynical tour of London's contemporary galleries.
In response to the recent financial crisis, members of the public were invited to show wrath or mercy to a host of characters. A selection of the renowned painter Joseph Wright's works were augmented with images of contemporaneous ceramics in order to interrogate their divergent themes. The
most recent work lifts characters from prints, and allowed them to inhabit the surrounding environment of Dr Freud's London house.
The conservative revolution: the Bolshoi archives
Authors: Sporton Gregory
Published: December 2012

One of the great cultural mysteries of the twentieth century is how a radical new form of government would come to be represented in cultural terms by an art form so associated with its conservative predecessor. From Imperial Russia to the Soviet Union, ballet managed to survive a transition
that was both creative and political. In this essay the reinvention of the Bolshoi Theatre in Moscow from Tsarist to Bolshevik is discovered through the archive materials of the Bolshoi itself. What were the dynamics that encouraged experimentation that of itself was then defined as failure
precisely because of its experimental nature? What was the formula that enabled the Bolshoi to represent the Soviet Union despite its representation of an aristocratic past that the Revolution had swept away? In a society where everything is politicized, how does ballet contribute to the polity?
From the threat of closure in the new regime's first days, through radical attempts to depict the proletariat in ballet action, to the descent into the creative stasis of socialist realism, we trace the path of ballet in the early Soviet period and its struggle to reform itself and represent
the new society around it.
‘Rew’ (Immémorial #6): what is surfacing and submerging
Authors: Weber Pascale
Published: December 2012

Immémorial is a work in progress which was begun in 1996, written, conceived and created by Pascale Weber and which deals with memory and identity. Its six versions question the interactions between technology, science and creation. 'Rew' is the title of the sixth version. As
an abbreviation of 'Rewind', it raises the spectre of travelling back in the past, of accessing our childhood secrets, of revisiting, maybe rewriting our identity. Immémorial #6: 'Rew' was shown in Marseille (Friche de la Belle de Mai) during the 2012 Music Festival, following a two-year
residency at the Experimental Music Group of Marseille [GMEM], Euphonia and the Music and Informatics Laboratory of Marseille [MIM].

The background and the lastest version of Immémorial allow us to investigate the relationship between technology, science and humanities. Science and
the computer offer an emotional, aesthetical energy, a capacity to nourish poetry and imagination; the artist may intuitively propose free hypotheses, confronting his artistic project with scientific questioning, instead of giving meaning to his work. Doing so, he collaborates in the development
of knowledge.

Immémorial proposes a taxonomy of models of recollections which form our identity and deals with the dynamic functioning of our memory. Conversely, the structure of the computer language used for distributing the video image and sound spatialization guide the construction
of the narrative and the return of the memorial experience in the device. Owing to the technical process of audio and visual spatialization, Immémorial projects the viewer into the heart of an environment, which is divided into 24 memorial moods based on poignant experiences, in order
to awaken long-term memory.

Immersive experiences pull us out of a reality too complex to grasp. This is the world narrowed in the heart of an enclosed space, a metaphor for a major societal issue: can we finally see the world as a plurality? Can we think outside of one’s body, from
other bodies, from a common body?
Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer
Authors: Seim Inge , Lubik Amy A , Lehman Melanie L , Tomlinson Nadine , Whiteside Eliza J , Herington Adrian C , Nelson Colleen C , Chopin Lisa K
Published: December 2012

Ghrelin is a multifunctional hormone, with roles in stimulating appetite and regulating energy balance, insulin secretion and glucose homoeostasis. The ghrelin gene locus (GHRL) is highly complex and gives rise to a range of novel transcripts derived from alternative first exons and internally spliced exons. The wild-type transcript encodes a 117 amino acid preprohormone that is processed to yield the 28 amino acid peptide ghrelin. Here, we identified insulin-responsive transcription corresponding to cryptic exons in intron 2 of the human ghrelin gene. A transcript, termed in2c-ghrelin (intron 2-cryptic), was cloned from the testis and the LNCaP prostate cancer cell line. This transcript may encode an 83 amino acid preproghrelin isoform that codes for ghrelin, but not obestatin. It is expressed in a limited number of normal tissues and in tumours of the prostate, testis, breast and ovary. Finally, we confirmed that in2c-ghrelin transcript expression, as well as the recently described in1-ghrelin transcript, is significantly upregulated by insulin in cultured prostate cancer cells. Metabolic syndrome and hyperinsulinaemia have been associated with prostate cancer risk and progression. This may be particularly significant after androgen deprivation therapy for prostate cancer, which induces hyperinsulinaemia, and this could contribute to castrate-resistant prostate cancer growth. We have previously demonstrated that ghrelin stimulates prostate cancer cell line proliferationin vitro. This study is the first description of insulin regulation of a ghrelin transcript in cancer and should provide further impetus for studies into the expression, regulation and function of ghrelin gene products.
Specific reduction of G6PT may contribute to downregulation of hepatic 11β-HSD1 in diabetic mice
Authors: Du Hanze , Liu Limei , Wang Ying , Nakagawa Yuichi , Lyzlov Alexei , Lutfy Kabirullah , Friedman Theodore C , Peng Xiaozhong , Liu Yanjun
Published: December 2012

Pre-receptor activation of glucocorticoids via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) has been identified as an important mediator of the metabolic syndrome. Hexose-6-phosphate dehydrogenase (H6PDH) mediates 11β-HSD1 amplifying tissue glucocorticoid production by driving intracellular NADPH exposure to 11β-HSD1 and requires glucose-6-phosphate transporter (G6PT (SLC37A4)) to maintain its activity. However, the potential effects of G6PT on tissue glucocorticoid production in type 2 diabetes and obesity have not yet been defined. Here, we evaluated the possible role of G6PT antisense oligonucleotides (G6PT ASO) in the pre-receptor metabolism of glucocorticoids as related to glucose homeostasis and insulin tolerance by examining the production of 11β-HSD1 and H6PDH in both maledb/+anddb/dbmouse liver tissue. We observed that G6PT ASO treatment ofdb/dbmice markedly reduced hepatic G6PT mRNA and protein levels and substantially diminished the activation of hepatic 11β-HSD1 and H6PDH. Reduction ofG6ptexpression was correlated with the suppression of both hepatic gluconeogenic enzymes G6Pase and PEPCK and corresponded to the improvement of hyperglycemia and insulin resistance indb/dbmice. Addition of G6PT ASO to mouse hepa1–6 cells led to a dose-dependent decrease in11B-Hsd1production. Knockdown of G6PT with RNA interference also impaired11B-Hsd1expression and showed comparable effects toH6pdhsiRNA on silencing ofH6pdhand11B-Hsd1expression in these intact cells. These findings suggest that G6PT plays an important role in the modulation of pre-receptor activation of glucocorticoids and provides new insights into the role of G6PT in the development of type 2 diabetes.
The Effect of Linkage Disequilibrium and Family Relationships on the Reliability of Genomic Prediction
Authors: Wientjes Yvonne C J , Veerkamp Roel F , Calus Mario P L
Published: December 2012

Although the concept of genomic selection relies on linkage disequilibrium (LD) between quantitative trait loci and markers, reliability of genomic predictions is strongly influenced by family relationships. In this study, we investigated the effects of LD and family relationships on reliability of genomic predictions and the potential of deterministic formulas to predict reliability using population parameters in populations with complex family structures. Five groups of selection candidates were simulated by taking different information sources from the reference population into account: (1) allele frequencies, (2) LD pattern, (3) haplotypes, (4) haploid chromosomes, and (5) individuals from the reference population, thereby having real family relationships with reference individuals. Reliabilities were predicted using genomic relationships among 529 reference individuals and their relationships with selection candidates and with a deterministic formula where the number of effective chromosome segments (Me) was estimated based on genomic and additive relationship matrices for each scenario. At a heritability of 0.6, reliabilities based on genomic relationships were 0.002 ± 0.0001 (allele frequencies), 0.022 ± 0.001 (LD pattern), 0.018 ± 0.001 (haplotypes), 0.100 ± 0.008 (haploid chromosomes), and 0.318 ± 0.077 (family relationships). At a heritability of 0.1, relative differences among groups were similar. For all scenarios, reliabilities were similar to predictions with a deterministic formula using estimated Me. So, reliabilities can be predicted accurately using empirically estimated Me and level of relationship with reference individuals has a much higher effect on the reliability than linkage disequilibrium per se. Furthermore, accumulated length of shared haplotypes is more important in determining the reliability of genomic prediction than the individual shared haplotype length.
A Simulation Study of Permutation, Bootstrap, and Gene Dropping for Assessing Statistical Significance in the Case of Unequal Relatedness
Authors: Cheng Riyan , Palmer Abraham A
Published: December 2012

We used simulations to evaluate methods for assessing statistical significance in association studies. When the statistical model appropriately accounted for relatedness among individuals, unrestricted permutation tests and a few other simulation-based methods effectively controlled type I error rates; otherwise, only gene dropping controlled type I error but at the expense of statistical power.
The Variance of Identity-by-Descent Sharing in the Wright–Fisher Model
Authors: Carmi Shai , Palamara Pier Francesco , Vacic Vladimir , Lencz Todd , Darvasi Ariel , Pe’er Itsik
Published: December 2012

Widespread sharing of long, identical-by-descent (IBD) genetic segments is a hallmark of populations that have experienced recent genetic drift. Detection of these IBD segments has recently become feasible, enabling a wide range of applications from phasing and imputation to demographic inference. Here, we study the distribution of IBD sharing in the Wright–Fisher model. Specifically, using coalescent theory, we calculate the variance of the total sharing between random pairs of individuals. We then investigate the cohort-averaged sharing: the average total sharing between one individual and the rest of the cohort. We find that for large cohorts, the cohort-averaged sharing is distributed approximately normally. Surprisingly, the variance of this distribution does not vanish even for large cohorts, implying the existence of “hypersharing” individuals. The presence of such individuals has consequences for the design of sequencing studies, since, if they are selected for whole-genome sequencing, a larger fraction of the cohort can be subsequently imputed. We calculate the expected gain in power of imputation by IBD and subsequently in power to detect an association, when individuals are either randomly selected or specifically chosen to be the hypersharing individuals. Using our framework, we also compute the variance of an estimator of the population size that is based on the mean IBD sharing and the variance in the sharing between inbred siblings. Finally, we study IBD sharing in an admixture pulse model and show that in the Ashkenazi Jewish population the admixture fraction is correlated with the cohort-averaged sharing.
Mutations to the piRNA Pathway ComponentAubergineEnhance Meiotic Drive of Segregation Distorter inDrosophila melanogaster
Authors: Gell Selena L , Reenan Robert A
Published: December 2012

Diploid sexual reproduction involves segregation of allelic pairs, ensuring equal representation of genotypes in the gamete pool. Some genes, however, are able to “cheat” the system by promoting their own transmission. The Segregation distorter (Sd) locus in Drosophila melanogaster males is one of the best-studied examples of this type of phenomenon. In this system the presence of Sd on one copy of chromosome 2 results in dysfunction of the non–Sd-bearing (Sd+) sperm and almost exclusive transmission of Sd to the next generation. The mechanism by which Sd wreaks such selective havoc has remained elusive. However, its effect requires a target locus on chromosome 2 known as Responder (Rsp). The Rsp locus comprises repeated copies of a satellite DNA sequence and Rsp copy number correlates with sensitivity to Sd. Under distorting conditions during spermatogenesis, nuclei with chromosomes containing greater than several hundred Rsp repeats fail to condense chromatin and are eliminated. Recently, Rsp sequences were found as small RNAs in association with Argonaute family proteins Aubergine (Aub) and Argonaute3 (AGO3). These proteins are involved in a germline-specific RNAi mechanism known as the Piwi-interacting RNA (piRNA) pathway, which specifically suppresses transposon activation in the germline. Here, we evaluate the role of piRNAs in segregation distortion by testing the effects of mutations to piRNA pathway components on distortion. Further, we specifically targeted mutations to the aub locus of a Segregation Distorter (SD) chromosome, using ends-out homologous recombination. The data herein demonstrate that mutations to piRNA pathway components act as enhancers of SD.
Caenorhabditis elegans PIG-1/MELK Acts in a Conserved PAR-4/LKB1 Polarity Pathway to Promote Asymmetric Neuroblast Divisions
Authors: Chien Shih-Chieh , Brinkmann Eva-Maria , Teuliere Jerome , Garriga Gian
Published: December 2012

Asymmetric cell divisions produce daughter cells with distinct sizes and fates, a process important for generating cell diversity during development. Many Caenorhabditis elegans neuroblasts, including the posterior daughter of the Q cell (Q.p), divide to produce a larger neuron or neuronal precursor and a smaller cell that dies. These size and fate asymmetries require the gene pig-1, which encodes a protein orthologous to vertebrate MELK and belongs to the AMPK-related family of kinases. Members of this family can be phosphorylated and activated by the tumor suppressor kinase LKB1, a conserved polarity regulator of epithelial cells and neurons. In this study, we present evidence that the C. elegans orthologs of LKB1 (PAR-4) and its partners STRAD (STRD-1) and MO25 (MOP-25.2) regulate the asymmetry of the Q.p neuroblast division. We show that PAR-4 and STRD-1 act in the Q lineage and function genetically in the same pathway as PIG-1. A conserved threonine residue (T169) in the PIG-1 activation loop is essential for PIG-1 activity, consistent with the model that PAR-4 (or another PAR-4-regulated kinase) phosphorylates and activates PIG-1. We also demonstrate that PIG-1 localizes to centrosomes during cell divisions of the Q lineage, but this localization does not depend on T169 or PAR-4. We propose that a PAR-4-STRD-1 complex stimulates PIG-1 kinase activity to promote asymmetric neuroblast divisions and the generation of daughter cells with distinct fates. Changes in cell fate may underlie many of the abnormal behaviors exhibited by cells after loss of PAR-4 or LKB1.
Biogenesis of RNA Polymerases II and III Requires the Conserved GPN Small GTPases in Saccharomyces cerevisiae
Authors: Minaker Sean W , Filiatrault Megan C , Ben-Aroya Shay , Hieter Philip , Stirling Peter C
Published: December 2012

The GPN proteins are a poorly characterized and deeply evolutionarily conserved family of three paralogous small GTPases, Gpn1, 2, and 3. The founding member, GPN1/NPA3/XAB1, is proposed to function in nuclear import of RNA polymerase II along with a recently described protein called Iwr1. Here we show that the previously uncharacterized protein Gpn2 binds both Gpn3 and Npa3/Gpn1 and that temperature-sensitive alleles of Saccharomyces cerevisiae GPN2 and GPN3 exhibit genetic interactions with RNA polymerase II mutants, hypersensitivity to transcription inhibition, and defects in RNA polymerase II nuclear localization. Importantly, we identify previously unrecognized RNA polymerase III localization defects in GPN2, GPN3, and IWR1 mutant backgrounds but find no localization defects of unrelated nuclear proteins or of RNA polymerase I. Previously, it was unclear whether the GPN proteins and Iwr1 had overlapping function in RNA polymerase II assembly or import. In this study, we show that the nuclear import defect of iwr1Δ, but not the GPN2 or GPN3 mutant defects, is partially suppressed by fusion of a nuclear localization signal to the RNA polymerase II subunit Rpb3. These data, combined with strong genetic interactions between GPN2 and IWR1, suggest that the GPN proteins function upstream of Iwr1 in RNA polymerase II and III biogenesis. We propose that the three GPN proteins execute a common, and likely essential, function in RNA polymerase assembly and transport.
Complete Remission Following Decitabine/Dendritic Cell Vaccine for Relapsed Neuroblastoma
Authors: Krishnadas Deepa Kolaseri , Shapiro Teresa , Lucas Kenneth
Published: December 2012

Patients with relapsed stage 4 neuroblastoma have an extremely poor long-term prognosis, making the investigation of new agents of interest. We report the outcome of the first patient treated in a phase 1 study for relapsed neuroblastoma, using the chemotherapy agent decitabine to upregulate cancer testis antigen expression, followed by a dendritic cell vaccine targeting the cancer testis antigens MAGE-A1, MAGE-A3, and NY-ESO-1. Our patient had persistent tumor in his bone marrow after completion of standard therapy for neuroblastoma, including multiagent chemotherapy, tumor resection, stem cell transplantation, radiation therapy, and anti-GD2 monoclonal antibodies. His marrow disease persisted despite chemotherapy, which was given while the vaccine was being produced. After 3 cycles of decitabine and vaccine, this patient achieved a complete remission and is now 1 year from his last treatment, with no evidence of tumor in his bone marrow or other sites. This patient was noted to have an increase in MAGE-A3–specific T cells. This is the first report combining demethylating chemotherapy to enhance tumor antigen expression followed by a cancer antigen vaccine.
Economic Evaluation of Pediatric Cancer Treatment: A Systematic Literature Review
Authors: Russell Heidi V. , Panchal Janki , VonVille Helena , Franzini Luisa , Swint J. Michael
Published: December 2012

OBJECTIVE:

Although there is a growing national focus on health care cost containment and accountability in resource utilization, childhood cancer therapy costs continue to increase without proportionate survival improvements. Economic evaluations (EEs) such as cost and/or cost effectiveness analysis may identify areas to improve resource efficiency. This review aims to identify and characterize the EE studies performed in this field.

METHODS:

We performed a structured literature search of the Medline, PubMed, and the National Health Service EE databases from 2000 to 2011. Concepts for the search included “cost analyses,” “child,” and “cancer.” Studies were limited to original research, comparison of 2 or more treatments using monetary units, English language, and originating from economically developed countries. Identified studies were assessed by the Drummond checklist and characterized by the therapy studied, data sources, and research perspectives.

RESULTS:

Forty studies met inclusion criteria. Eleven studied chemotherapy, surgery, or radiation. Twenty-nine studied supportive measures such as growth factor support or treatment of infection. The median Drummond score was 6 of 10 (range, 2–9). Only 15 (36%) included treatment outcomes when comparing costs. Methodological limitations were common.

CONCLUSIONS:

A wide variety of topics and methodological limitations made comparisons between studies difficult. Strategies for increasing the generalizability of future EE studies are presented. Substantial opportunity exists for EE research in childhood cancer.
Validation of a Migraine Interview for Children and Adolescents
Authors: Lateef Tarannum , Cui Lihong , Heaton Leanne , Nakamura Erin F. , Ding Jinhui , Ahmed Sameer , Merikangas Kathleen R.
Published: December 2012

OBJECTIVE:

To date there are no structured interviews to ascertain the diagnostic criteria for headache in children. The objective of this study was to assess the validity of the Diagnostic Interview of Headache Syndromes–Child Version (DIHS-C), which was developed at the National Institute of Mental Health for a community-based family study of headache syndromes and comorbid disorders.

METHODS:

The DIHS-C is a fully structured diagnostic interview composed of an open-ended clinical history, modules with key symptoms for each of the major headache subtypes, and associated impairment, duration, frequency, course, and treatment. This article presents the validation of the interview in a sample of 104 children evaluated as part of a community-based family study of migraine.

RESULTS:

The sensitivity of interview diagnosis compared with an expert neurologist’s diagnosis of migraine was 98%, and the specificity was 61%. Similar levels of sensitivity and specificity were found by gender and age of the children.

CONCLUSIONS:

The DIHS-C provides a new tool that can enhance the reliability of pediatric diagnoses in both clinical and community settings.
Weight-Based Victimization: Bullying Experiences of Weight Loss Treatment–Seeking Youth
Authors: Puhl Rebecca M. , Peterson Jamie Lee , Luedicke Joerg
Published: December 2012

OBJECTIVE:

Few studies have comprehensively examined weight-based victimization (WBV) in youth, despite its serious consequences for their psychosocial and physical health. Given that obese and treatment-seeking youth may be highly vulnerable to WBV and its negative consequences, the current study provides a comprehensive assessment of WBV in a weight loss treatment–seeking sample.

METHODS:

Adolescents (aged 14–18 years; N = 361) enrolled in 2 national weight loss camps were surveyed. An in-depth assessment of WBV was conducted by using an online survey, in which participants indicated the duration, typical locations, frequent perpetrators, and forms of WBV they had experienced.

RESULTS:

Findings indicate that 64% of the study participants reported WBV at school, and the risk of WBV increased with body weight. Most participants reported WBV enduring for 1 year (78%), and 36% were teased/bullied for 5 years. Peers (92%) and friends (70%) were the most commonly reported perpetrators, followed by adult perpetrators, including physical education teachers/sport coaches (42%), parents (37%), and teachers (27%). WBV was most frequently reported in the form of verbal teasing (75%–88%), relational victimization (74%–82%), cyberbullying (59%–61%), and physical aggression (33%–61%). WBV was commonly experienced in multiple locations at school.

CONCLUSIONS:

WBV is a prevalent experience for weight loss treatment–seeking youth, even when they are no longer overweight. Given the frequent reports of WBV from adult perpetrators in addition to peers, treatment providers and school personnel can play an important role in identifying and supporting youth who may be at risk for pervasive teasing and bullying.
Infantile Hemangiomas: An Update on Pathogenesis and Therapy
Authors: Chen Tina S. , Eichenfield Lawrence F. , Friedlander Sheila Fallon
Published: December 2012

Infantile hemangiomas (IHs) are the most common vascular tumors of childhood, affecting ∼5% of all infants. Although most lesions proliferate and then involute with minimal consequence, a significant minority can be disfiguring, functionally significant, or, rarely, life-threatening. Recent discoveries concerning hemangioma pathogenesis provide both an improved understanding and more optimal approach to workup and management. Important detrimental associations can be seen with IH, such as significant structural anomalies associated with segmental IH. Standards of care have dramatically changed evaluation and management of hemangiomas. The goal of timely recognition and therapy is to minimize or eliminate long-term sequelae. New modalities, such as oral propranolol, provide the caregiver with better therapeutic options, which can prevent or minimize medical risk or scarring, but the side effect profile and risk-benefit ratio of such interventions must always be evaluated before instituting therapy.
Child and Parental Reports of Bullying in a Consecutive Sample of Children With Food Allergy
Authors: Shemesh Eyal , Annunziato Rachel A. , Ambrose Michael A. , Ravid Noga L. , Mullarkey Chloe , Rubes Melissa , Chuang Kelley , Sicherer Mati , Sicherer Scott H.
Published: December 2012

OBJECTIVE:

The social vulnerability that is associated with food allergy (FA) might predispose children with FA to bullying and harassment. This study sought to quantify the extent, methods, and correlates of bullying in a cohort of food-allergic children.

METHODS:

Patient and parent (83.6% mothers) pairs were consecutively recruited during allergy clinic visits to independently answer questionnaires. Bullying due to FA or for any cause, quality of life (QoL), and distress in both the child and parent were evaluated via questionnaires.

RESULTS:

Of 251 families who completed the surveys, 45.4% of the children and 36.3% of their parents indicated that the child had been bullied or harassed for any reason, and 31.5% of the children and 24.7% of the parents reported bullying specifically due to FA, frequently including threats with foods, primarily by classmates. Bullying was significantly associated with decreased QoL and increased distress in parents and children, independent of the reported severity of the allergy. A greater frequency of bullying was related to poorer QoL. Parents knew about the child-reported bullying in only 52.1% of the cases. Parental knowledge of bullying was associated with better QoL and less distress in the bullied children.

CONCLUSIONS:

Bullying is common in food-allergic children. It is associated with lower QoL and distress in children and their parents. Half of the bullying cases remain unknown to parents. When parents are aware of the bullying, the child’s QoL is better. It is important to proactively identify and address cases in this population.
Obtaining Consent from Both Parents for Pediatric Research: What Does “Reasonably Available” Mean?
Authors: Nelson Daniel K. , Skinner Debra , Guarda Sonia , Choudhury Summer , Sideris John , Barnum Leah , Ten Haagen Kristy , Heyward Quetrell , Bailey Donald B.
Published: December 2012

OBJECTIVE:

Circumstances surrounding parental availability and decision-making were examined in the setting of a research protocol involving newborn screening (NBS) for fragile X syndrome, in which the institutional review board (IRB) had determined that consent (permission) was required from both parents.

METHODS:

A survey was conducted with 3001 families who were approached to participate in optional NBS. In addition to basic demographics, observational notes detailed the reasons why fathers were not present or deemed “not reasonably available” (per IRB regulations), and content analysis identified the factors for this lack of availability. Logistic regression models estimated the likelihood that both parents would agree to enroll their infant in the screening project.

RESULTS:

Fathers were not present in 589 cases, including 158 in which fathers were ultimately determined to be not reasonably available. Primary reasons for father’s unavailability were deployment with the military, incarceration, living out of state, or not involved in the mother’s life. In cases in which both parents were available, 64% agreed to enroll in the NBS study. Criteria to guide researchers in making required determinations were developed from consultations with IRB officials and legal counsel.

CONCLUSIONS:

In a large-scale population-based study, 19.6% of fathers were absent for the consent process. Scenarios encountered underscore the complexity of parental relations and their implications for obtaining consent for research involving children. The algorithm developed may serve as a useful tool for others in applying the regulatory requirements for dual parental permission.