bluuebunny/crossref_metadata_2025 huggingface dataset:
Ideias da Arquitectura Portuguesa em viagem
Authors: Silva Cristina Emília , Furtado Gonçalo
Published: October 2015

Português No presente artigo, propomo-nos delinear alguns itinerários que a Arquitectura Portuguesa percorreu fora do território nacional e identificar os protagonistas com quem viajou rumo ao reconhecimento internacional que detém actualmente. Referência será feita a casos como Eduardo Anahory e a publicação World Architecture em Inglaterra, entre outras da década de 50 e 60. Expor-se-á como as viagens do arquitecto Nuno Portas e o interesse de arquitectos e editores do Sul da Europa, como por exemplo Oriol Bohigas, Vittorio Gregotti, Bruno Alfieri ou Bernard Huet, oriundos de Espanha, Itália e França, ou os encontros em seminários com a presença de nomes como Aldo Rossi, entre outros, fizeram do ano de 1976 um ano de autêntica viragem, de colocação da Arquitectura Portuguesa sob os holofotes da cena internacional arquitectónica. Em grande medida, os arquitectos Portugueses mostraram e ensinaram então, aos seus congéneres internacionais, hipóteses de saídas para a chamada Crise do Movimento Moderno. E, seriam necessários poucos anos, para que passássemos de uma situação de ser forçados a sair, para atrairmos outros a viajarem ao interior do nosso País e Arquitectura.   Inglês The present article aims at presenting some of the itineraries that the Portuguese Architecture has gone through abroad while identifying the main protagonists it travelled with towards the achievement of a widely international recognition. It will be referred cases like Eduardo Anahory and the World Architecture edition in England, among others of the 50s and 60s. The importance of trips taken by the architect Nuno Portas and the interest of architects and editors from South of Europe like, for instance, Oriol Bohigas, Vittorio Gregotti, Bruno Alfieri or Bernard Huet, from Spain, Italy and France, or the meetings and seminars arranged by and with the presence of relevant names like Aldo Rossi, among others contributed decisively to make the year of 1976 a turning point. The international attention was focussed on the Portuguese Architecture putting it under the lights of the international architectural scene. The Portuguese architects showed and taught then to their international colleagues, possibilities for the solution of the so-called Crisis of the Modern Movement. Within a few years, the situation was reversed: it was our turn to attract them to visit our country and to know its Architecture.
Un Doble del Mundo
Authors: Mansilla Luis
Published: October 2015

Partiendo del párrafo final original del diario de Viaje a Oriente de Le Corbusier, y su posterior correción para la publicación en 1965, se discute la cercanía de LC a Brueghel, y a través de él, a la medida y la Naturaleza.
Alexandre Alves Costa: A Viagem
Authors: Costa Alexandre Alves
Published: October 2015

Esta é uma exposição que corresponde ao desafio que o Departamento de Arquitectura da FCTUC lançou ao Professor Alexandre Alves Costa para comissariar e conceber uma mostra subordinada ao tema “a minha Escola”.

Com o título Alexandre Alves Costa: a Viagem. À memória de Fernando Távora, percorre os caminhos que consolidam a memória e a identidade do Departamento, na altura em que celebra os vinte anos de existência, mas, acima de tudo, oferece-nos um contributo essencial para reflectirmos sobre a actual condição da arquitectura, no contexto universitário.

Alexandre Alves Costa, Professor Jubilado Catedrático da Faculdade de Arquitectura do Porto e Professor Catedrático Convidado do DARQ, é hoje uma referência fundamental do ensino da arquitectura. Os princípios orientadores da sua actividade pedagógica constroem-se e consolidam-se ao longo de um percurso que privilegia a história como matriz cultural e ontológica das práticas arquitectónicas. O Projecto e a História da Arquitectura são as áreas às quais, preferencialmente, se tem dedicado.

Esta exposição é uma estação desse percurso. Talvez mesmo por essa razão, é concebida como uma VIAGEM pelos seus interesses, pelos seus temas de ensino, pelas suas escolas. Mas é também um VIAGEM através da sua relação com o Professor Arquitecto Fernando Távora, uma relação que, em grande medida, foi consolidada em Coimbra, na construção do que é hoje o Departamento de Arquitectura.
Regarding Rules: From Rimini to Rio
Authors: Knight Terry
Published: October 2015

The legacy of Alberti’s 15th century treatise, De re aedificatoria(Alberti, 1988), on architectural theory and practice up to the present day is profound and wide-ranging. Indeed, the story of building over the last five and a half centuries is, in part, the story of the diverse interpretations, adaptations, and transformations of the rules of building that Alberti derived from classical architecture and laid down in his treatise. Interestingly, this story of transformations begins with Alberti himself — with his own adaptations and departures from classical rules within his own design practice and for his own time. In so doing, Alberti set the stage for others to transform rules, precedents, and traditions in innovative and context-specific ways.In this paper, design rules and transformations are introducedthrough the ideas and work of Alberti, and then expanded througha computational lens, specifically, through the lens of shape grammars.Four computational strategies for transforming designs to produce new ones are outlined and illustrated through prior shape grammar studies.In each strategy, the analysis of precedents is the impetus for design, and rules are the basis for practice. Though the computational format of shape grammars rules is unique and contemporary, the goals and potentials of shape grammars are very much in the spirit of Alberti.
Interactive Stereoscopic Visualization of Alberti Architectural Models
Authors: Araújo Bruno , Mendes Daniel , Fonseca Fernando , Ferreira Alfredo , Jorge Joaquim A , Costa Eduardo Castro e , Figueiredo Bruno , Coutinho Filipe , Duarte José
Published: October 2015

The widespread adoption of multi-touch devices and the vulgarization of inexpensive and non-intrusive tracking solutions allow the design of new experiences for museum visitors. This allows users to visualize and interact with 3D models, overcoming the physical limitations of scale models and avoiding direct manipulations with valuable artifacts. In this paper we present a semi-immersive environment to visualize digital reproductions of Leon Battista Alberti influenced buildings in a museum exhibition. Combining affordable tracking technology and stereoscopic visualization, virtual models can be rendered as they were lying above the surface. Using a touch enabled surface and hands and fingers tracking, we allow exhibition visitors to interact with the virtual content in a non-intrusive manner. It also enables visitors to create their own custom Alberti temple, changing its columns, front and body, following the strict Alberti treatise rules, and then observe the impact of the changes on the complete model. With the feedback we attained in the exhibition, we showed, once again, that virtual reality can improve museum experiences, making them more appealing and interactive, offering unique ways to explore content, which posters and physical models cannot provide.
The albertian meaning of 'villa'. A reading key for the rehabilitation of the “montes” alentejanos.
Authors: Moreia e Sá Mariana Ramos
Published: October 2015

PT Observe-se o título: o termo “montes” encontra-se entre aspas devido à presente dificuldade em encontrar uma designação própria que permita caracterizar o objecto de estudo do Projecto de Investigação de Doutoramento em curso. Esta dificuldade surge pela existência de três realidades distintas em contexto alentejano: ‘quinta’, ‘monte’ e ‘herdade’. De forma a encontrar um nome para intitular esta realidade arquitectónica do mundo rural, recorreu-se à tradução, enquanto processo próprio de investigação: a tratadística clássica foi chamada a informar a contemporânea. Assim, percebeu-se que seria pertinente estudar o tratado ‘De Re Ædificatoria’ de Leon Battista Alberti, uma vez que caracteriza, este tipo de realidade. Optou-se pela leitura de quatro traduções, em línguas latinas, de três passagens do Livro V – ‘Edifícios para fins particulares’: a tradução de Giovanni Orlandi, a de Javier Fresnillo Núñez, a de Pierre Caye e Françoise Choay, bem como a de Arnaldo Espírito Santo e Mário Krüger. O tipo de “monte” que pretendo investigar, corresponde a uma arquitectura aparentemente anónima, mas que tem na sua génese um pensamento arquitectónico. Um dos ‘rastos escritos’ que possui, foi encontrado no tratado de Alberti, dando-lhe a ‘voz teórica’ que lhe falta, para lhe permitir ‘dizer aquilo que não é capaz’.   EN Note the title: the term “montes” is in inverted commas due to the difficulty in finding an own designation that allows characterizing the study object of the PhD Research. This difficulty arises by the existence of three distinct realities in the ‘alentejano’ context: ‘quinta’, ‘monte’ and ‘herdade’. In order to find a name to title this architectural reality, we resorted to the translation, as a research process itself: the classical treatises were called to inform the contemporary one. In this way, we realized that it would be appropriate to study the treaty ‘De Re Ædificatoria’ of Leon Battista Alberti, once characterizes this type of reality. We decided reading four translations from three passages of the Book V – “Buildings for private purposes”, in Latin languages that are the translation of Giovanni Orlandi, of Javier Fresnillo Núñez, of Pierre Caye and Françoise Choay, and of Arnaldo Espírito Santo and Mário Krüger. The type of “monte” that we intend to investigate, corresponds to an apparently anonymous architecture, but that has in its genesis an architectural thinking. One of its ‘written tracks’ has been found in Alberti’s treatise, given the theoretical voice that lacks, in order to allow it ‘to say what can not’.
7. Bremer eBook-Tag
Authors: Rauchmann Sabine
Published: October 2015

Seit 2006 richtet der Bibliotheksdienstleister Missing Link den Bremer eBook-Tag aus. Auf der diesjährigen Veranstaltung stellten Bibliothekare, Verlagsvertreter und Buchhändler ihre Erfahrungen mit der nutzergestützten (EBS) und der nutzergesteuerten (PDA) Erwerbung von E-Books vor. Weiterhin präsentierten drei Verlage ihre E-Book-Strategie. Der vorliegende Beitrag bietet einen Überblick über die Veranstaltung und fasst die Vorträge zusammen.
Two letters by Brutus and Cassius to Mark Antony: different people, different times, different styles
Authors: Calboli Gualtiero
Published: October 2015

Between end of May and beginning of August 44 M. Junius Brutus, praetor urbanus, and C. Cassius Longinus, praetor peregrinus, sent two letters to M. Antony who was consul. These letters were different in content and style but also the two senders were different. If we take into account the facts of this time we see that the situation in Rome changed and M. Antony gave up his previous position (assumed 17 March 44), which was oriented towards the
First Principles Study of Electronic Structure, Magnetic, and Mechanical Properties of Transition Metal Monoxides TMO(TM=Co and Ni)
Authors: Cinthia Arumainayagam Jemmy , Rajeswarapalanichamy Ratnavelu , Iyakutti Kombiah
Published: October 2015

The ground-state properties, electronic structure, magnetic and mechanical properties of cobalt oxide (CoO) and nickel oxide (NiO) are investigated using generalised gradient approximation parameterised by Perdew–Burke–Ernzerhof (GGA-PBE) and GGA-PBE+U formalisms. These oxides are found to be stable in the antiferromagnetic (AFM) state at normal pressure. The computed lattice parameters are in agreement with the experimental and other theoretical works. Pressure-induced magnetic transition from AFM to ferromagnetic (FM) state is predicted in NiO at a pressure of 84 GPa. Both these compounds are found to be mechanically stable in the AFM state at normal pressure.
The aspirations of Albanian archaeology
Authors: Hodges Richard
Published: October 2015

These words, published in the pages ofAntiquitymore than 20 years ago, belie the dark depths into which Albanian archaeologists were plunged with the transition to democracy during 1991–1992. Despite the long bread queues that characterised Albanian life before the Iron Curtain fell, Albanian archaeologists engaged in missions across the country—nearly 50 in 1988. The charmed life of Albania's archaeologists until 1991 is easily explained. Between 1944 and 1985, the dictator Enver Hoxha invested in archaeology to secure an Illyrian myth for an unstable republic, which, in 1913, was carved out of the western Ottoman Empire. The first generation of communist archaeologists was trained in the Soviet Union; they in turn mentored subsequent generations. As a result, with the advent of democracy, almost no archaeologist had first-hand experience of Western European or American archaeology. The few who had engaged with Western Europe (Neritan Ceka, Aleksander Meksi, Genc Pollo) changed careers and entered politics (Hodges 2014). After the first elections, the 1990s, bearing the bitter scars of communism, were exceedingly confusing and practically complicated for Albania's archaeologists. And yet the Institute of Archaeology has tenaciously held its place in Albanian society, and, under the leadership of the adroit Muzafer Korkuti (Hodges & Bejko 2006), and now Luan Përzhita, there has been a steadying direction that can be readily detected in this encyclopaedic volume arising from a conference held during the centenary celebrations of the Republic of Albania.
Mainland Southeast Asia: towards a new theoretical approach
Authors: Oxenham M.F.
Published: October 2015

Higham's paper calls for a consensus on the chronology of the Neolithic through to the Bronze period in mainland Southeast Asia (MSEA), articulating a series of questions relating to human mobility, subsistence and socio-cultural organisation within this timeframe. Having worked in Vietnam for 20 years, and being very familiar with the ‘Vietnamese’ Neolithic, I must admit to having paid little attention to the so-called LCM (long chronology); this is because the chronology suggested by its (limited number of) proponents is simply inconsistent with what is known of the development of the Neolithic in Vietnam and the later emergence of bronze technology. In terms of the broader chronology of MSEA, my colleagues and I (e.g. Oxenham et al. 2015) have stressed the observation of a virtual eruption of Neolithic sites across the region c. 4000 BP, overlapping with the terminal phase of the southern Chinese Neolithic, which no doubt fuelled (in terms of genes and technology) the major transformations observed among its more southerly neighbours.
EDITORIAL
Authors: Scarre Chris
Published: October 2015

The summer of 2015 marks the seventieth anniversary of one of the tragic turning points in recent human history: the detonation of the two atomic bombs at Hiroshima and Nagasaki on 6 and 9 August 1945. Those events were soon followed by the Cold War and the build-up of nuclear arsenals capable of obliterating the world population several times over.
On the relevance of the European Neolithic
Authors: Bentley R. Alexander , O’Brien Michael J. , Manning Katie , Shennan Stephen
Published: October 2015

Sustainability, culture change, inequality and global health are among the much-discussed challenges of our time, and rightly so, given the drastic effects such variables can have on modern populations. Yet with many populations today living in tightly connected geographic communities—cities, for example—or in highly networked electronic communities, can we still learn anything about societal challenges by studying simple farming communities from many thousands of years ago? We think there is much to learn, be it Malthusian pressures and ancient societal collapse, the devastating effects of European diseases on indigenous New World populations or endemic violence in pre-state societies (e.g. Pinker 2012). By affording a simpler, ‘slow motion’ view of processes that are greatly accelerated in this century, the detailed, long-term record of the European Neolithic can offer insight into many of these fundamental issues. These include: human adaptations to environmental change (Palmer & Smith 2014), agro-pastoral innovation, human population dynamics, biological and cultural development, hereditary inequality, specialised occupations and private ownership.
Estimation of Additive, Dominance, and Imprinting Genetic Variance Using Genomic Data
Authors: Lopes Marcos S , Bastiaansen John W M , Janss Luc , Knol Egbert F , Bovenhuis Henk
Published: October 2015

Traditionally, exploration of genetic variance in humans, plants, and livestock species has been limited mostly to the use of additive effects estimated using pedigree data. However, with the development of dense panels of single-nucleotide polymorphisms (SNPs), the exploration of genetic variation of complex traits is moving from quantifying the resemblance between family members to the dissection of genetic variation at individual loci. With SNPs, we were able to quantify the contribution of additive, dominance, and imprinting variance to the total genetic variance by using a SNP regression method. The method was validated in simulated data and applied to three traits (number of teats, backfat, and lifetime daily gain) in three purebred pig populations. In simulated data, the estimates of additive, dominance, and imprinting variance were very close to the simulated values. In real data, dominance effects account for a substantial proportion of the total genetic variance (up to 44%) for these traits in these populations. The contribution of imprinting to the total phenotypic variance of the evaluated traits was relatively small (1–3%). Our results indicate a strong relationship between additive variance explained per chromosome and chromosome length, which has been described previously for other traits in other species. We also show that a similar linear relationship exists for dominance and imprinting variance. These novel results improve our understanding of the genetic architecture of the evaluated traits and shows promise to apply the SNP regression method to other traits and species, including human diseases.
Estimating Trait Heritability in Highly Fecund Species
Authors: Davies Sarah W , Scarpino Samuel V , Pongwarin Thanapat , Scott James , Matz Mikhail V
Published: October 2015

Increasingly, researchers are interested in estimating the heritability of traits for nonmodel organisms. However, estimating the heritability of these traits presents both experimental and statistical challenges, which typically arise from logistical difficulties associated with rearing large numbers of families independently in the field, a lack of known pedigree, the need to account for group or batch effects, etc. Here we develop both an empirical and computational methodology for estimating the narrow-sense heritability of traits for highly fecund species. Our experimental approach controls for undesirable culturing effects while minimizing culture numbers, increasing feasibility in the field. Our statistical approach accounts for known issues with model-selection by using a permutation test to calculate significance values and includes both fitting and power calculation methods. We further demonstrate that even with moderately high sample-sizes, the p-values derived from asymptotic properties of the likelihood ratio test are overly conservative, thus reducing statistical power. We illustrate our methodology by estimating the narrow-sense heritability for larval settlement, a key life-history trait, in the reef-building coral Orbicella faveolata. The experimental, statistical, and computational methods, along with all of the data from this study, are available in the R package multiDimBio.
A Nonsense Variant in COL6A1 in Landseer Dogs with Muscular Dystrophy
Authors: Steffen Frank , Bilzer Thomas , Brands Jan , Golini Lorenzo , Jagannathan Vidhya , Wiedmer Michaela , Drögemüller Michaela , Drögemüller Cord , Leeb Tosso
Published: October 2015

A novel canine muscular dystrophy in Landseer dogs was observed. We had access to five affected dogs from two litters. The clinical signs started at a few weeks of age, and the severe progressive muscle weakness led to euthanasia between 5 and 15 months of age. The pedigrees of the affected dogs suggested a monogenic autosomal-recessive inheritance of the trait. Linkage and homozygosity mapping indicated two potential genome segments for the causative variant on chromosomes 10 and 31 harboring a total of 4.8 Mb of DNA or 0.2% of the canine genome. Using the Illumina sequencing technology, we obtained a whole-genome sequence from one affected Landseer. Variants were called with respect to the dog reference genome and compared with the genetic variants of 170 control dogs from other breeds. The affected Landseer dog was homozygous for a single, private nonsynonymous variant in the critical intervals, a nonsense variant in the COL6A1 gene (Chr31:39,303,964G>T; COL6A1:c.289G>T; p.E97*). Genotypes at this variant showed perfect concordance with the muscular dystrophy phenotype in all five cases and more than 1000 control dogs. Variants in the human COL6A1 gene cause Bethlem myopathy or Ullrich congenital muscular dystrophy. We therefore conclude that the identified canine COL6A1 variant is most likely causative for the observed muscular dystrophy in Landseer dogs. On the basis of the nature of the genetic variant in Landseer dogs and their severe clinical phenotype these dogs represent a model for human Ullrich congenital muscular dystrophy.
Diet and Implant Complications
Authors: Flanagan Dennis
Published: October 2015

A hard or coarse diet may impart a substantial off-axial load to dental implant-supported prostheses and may induce a component, implant midbody fracture or late loss of integration. This may be especially true when there is a large crown to implant ratio. A patient who is able to generate an excessive bite force along with chronic cyclic loading with hard or coarse foods may have implant body or component fractures. There are no established parameters for crown to implant ratio or for detrimental bite loads. Implant longevity may be dependent on many factors, including the supporting bone quality and volume, crown to implant ratio, implant width and length, the prosthetic occlusal scheme and bite force/arch location, and the patient's dietary load.
Effects of Pediatric Training for Detecting Signs of Developmental Problems
Authors: Morais Ana Silvia de , Bronzatto Edna Márcia Koizume , Lerner Rogério , Kupfer Maria Cristina Machado
Published: October 2015

A multicenter study (2004-2008) of clinical Risk Indicators for Child Development (IRDI) created and validated 31 indicators that can be observed in the initial 18 months post birth, with a statistically significant ability to predict developmental problems and psychic risk. Pediatricians were trained to collect data using the instrument. We discuss what remained for the pediatricians by interviewing a pediatrician who attended the course. The interview was analyzed from an institutional discourse perspective, revealing an objective/subjective duality and a split between prior and acquired knowledge. The ward emergency scenario does not provide enough time for a guided look at the indicators; indicators associated with parental function had a greater impact. The course increased his pleasure in his clinical practice, although his prior knowledge was limited. We suggest investigating the extent and limits of the effects of IRDI-oriented training for medical practice.
Adolescência e Tendência Antissocial: o Rap como Expressão de uma Privação Emocional
Authors: Silva Cláudia Yaísa Gonçalves da , Milani Rute Grossi
Published: October 2015

O presente estudo objetiva refletir sobre a tendência antissocial no adolescente/jovem, por meio da análise do conteúdo descrito nas letras de músicas de rap brasileiro, as quais em geral surgem carregadas de revolta, inconformismo, denúncias sociais e esperança. A pesquisa se caracteriza como exploratória, documental e qualitativa. Para tanto, foi realizada análise de conteúdo das letras, e posterior discussão embasada na teoria de Donald Woods Winnicott, buscando nos trechos das músicas indícios referentes a privações ambientais e o sentido que as letras carregam no contexto do comportamento antissocial. Na análise de conteúdo encontraram-se três categorias: a falha ambiental como princípio para a tendência antissocial, a tendência antissocial enquanto esperança de reparação, e o rappara além da música. Nos excertos das letras de rapselecionadas, os comportamentos antissociais mostraram-se enquanto saída emocional encontrada pelos adolescentes/jovens com histórico de privação, fazendo-os adotarem uma conduta desafiadora socialmente como forma de buscar uma contenção externa para reparar a falha vivenciada antes por alguma figura referencial. Conclui-se que o rap se instaurou como solução positiva para a expressão dos sentimentos e a conquista de uma identidade e reconhecimento social frente aos pares.
Temas das Brincadeiras de Papéis na Educação Infantil
Authors: Marcolino Suzana , Mello Suely Amaral
Published: October 2015

O objetivo do artigo é discutir os temas da brincadeira de papéis sociais na Educação Infantil, revelados por meio de análise conduzida com base nos estudos da Psicologia Histórico-Cultural. Para Elkonin, na idade pré-escolar a brincadeira atinge o auge de seu desenvolvimento, e se caracteriza pela criação de uma situação imaginária, pela presença de regras e de papéis sociais. Foram observadas situações de brincadeira de crianças de quatro anos e meio a cinco anos e meio em 11 escolas da rede municipal de uma cidade de médio porte do interior paulista. A partir do registro das observações, foram identificadas 27 cenas de brincadeira de papéis. A análise dos dados colhidos confirma a tese de Elkonin de que o desenvolvimento da brincadeira de papéis relaciona-se com o que a criança conhece de sua realidade, e indica a necessidade do estabelecimento de certas condições para que esse desenvolvimento ocorra na Educação Infantil. Nesse sentido, discute-se a necessidade de uma mediação do professor calcada na compreensão da riqueza de implicações que a brincadeira de papéis tem para a formação da pessoa.
A Phase Ib/II Study of Gemcitabine and Docetaxel in Combination With Pazopanib for the Neoadjuvant Treatment of Soft Tissue Sarcomas
Authors: Munhoz Rodrigo R. , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary L. , Chi Ping , Carvajal Richard D. , Singer Samuel , Crago Aimee M. , Landa Jonathan , Healey John H. , Qin Li-Xuan , Hameed Meera , Ezeoke Marietta O. , Singh Arun S. , Agulnik Mark , Chmielowski Bartosz , Luke Jason J. , Van Tine Brian A. , Schwartz Gary K. , Tap William D. , Dickson Mark A.
Published: October 2015

Author Summary

Lessons Learned

Our results highlight some of the challenges in the management of soft tissue sarcomas, which requires close cooperation between surgeons and medical oncologists and a careful selection of patients. The incidence of hepatotoxicity was a concerning finding and had been previously reported in patients treated with pazopanib. Although pharmacokinetic analysis was not part of this study, concomitant treatment with pazopanib has been recently reported to increase docetaxel exposure, which may explain the increased toxicity of combination regimens. It remains possible that lower doses of combined gemcitabine, docetaxel, and pazopanib may be tolerable. However, caution should be exercised in future trials investigating similar combinations.

Background.

For extremity soft tissue sarcomas (STS), surgical resection remains the standard of care, and the addition of chemotherapy is controversial. This was a phase Ib/II trial of neoadjuvant therapy for patients with STS.

Methods.

Patients with high grade, extremity STS of >8 cm and amenable to definitive resection were treated with up to four 21-day cycles of 900 mg/m2 gemcitabine on days 1 and 8, 75 mg/m2 docetaxel on day 8, and 400 mg of pazopanib daily (GDP), followed by surgery and, if indicated, radiation therapy. Primary and secondary endpoints (phase Ib portion) were the safety and rate of pathologic response.

Results.

The trial was discontinued because of slow accrual after inclusion of five patients (leiomyosarcoma: two; undifferentiated pleomorphic sarcoma: three). Two patients completed four treatment cycles: one underwent surgery and one had insufficient response and received additional therapies. Three patients discontinued treatment because of toxicity. Grade 3 adverse events included hypertension, fatigue, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation, hoarseness, and myelotoxicity. There were no complete or partial responses. One patient had ≥90% pathologic response. Among four patients who underwent resection, three remain free of disease, and one patient eventually relapsed.

Conclusion.

GDP combination used in the neoadjuvant setting resulted in significant toxicity; despite pathologic responses, no objective responses occurred.
Susan Bates, M.D., and Antonio “Tito” Fojo, M.D., Ph.D.: Thirty Years of Research, Discovery, Service, and Mentorship at the National Cancer Institute
Authors: Mailankody Sham , Prasad Vinayak
Published: October 2015

The authors pay tribute to Dr. Susan Bates's and Dr. Antonio “Tito” Fojo's careers of more than 30 years with the National Cancer Institute.
Efficacy, Time, Cost and Radiation Exposure of Combined Limited Fluoroscopy with Non-fluoroscopic Three-dimensional Imaging in Paediatric Supraventricular Tachycardia Ablation – Best of Both Worlds
Authors: Sanil Yamuna , Singh Harinder R , Webster Paul A , Karpawich Peter P ,   Assistant Professor of Pediatrics, Section of Cardiology, The Children’s Hospital of Michigan, Wayne State University School of Medicine, Detroit, US,   Professor of Pediatrics, Section of Cardiology, Children’s Hospital of San Antonio, Texas, US,   Chief Technician, Cardiac Catheterization Laboratory, The Children´s Hospital of Michigan, Detroit, US,   Director, Cardiac Elecrophysiology, The Children´s Hospital of Michigan and Professor, Wayne State University School of Medicine, Detroit, US
Published: October 2015

Objective: Catheter ablation for supraventricular tachycardias (SVTs) traditionally has utilised fluoroscopic imaging (FI). However, radiation concerns have recently contributed to the evolution of non-fluoroscopic three-dimensional imaging (3DI) systems. A few recent studies have advocated non-FI in lieu of FI. To date, there are only a few studies reporting use of limited FI with 3DI usage in children undergoing SVT ablations. This study evaluates time, efficacy, cost and safety of limited FI plus 3DI for SVT ablation in the young.Methods: Electrophysiology study (EPS) and ablation data for standard forms of SVT from October 2009 to June 2012 were reviewed. Patient radiation time, radiation dose area product (DAP), EPS time, anaesthesia duration and cost, and ablation success rates were evaluated.Results: A total of 81 patients (mean age 13.2 ± 3.4 years) underwent ablation. Type of SVT, gender, age, acute success, adverse events and recurrences were recorded post-ablation for over 2.5 years. Acute procedural success was 93.8 %. Of these, chronic sustained success was 85.5 %. As expected, limited FI plus 3DI was associated with some radiation exposure (2.47 ± 2.78 milliGray-m2) but less than historically associated with paediatric tachycardia ablations.Conclusion: A conscious awareness to use limited FI combined with 3DI is associated with excellent long-term success, lack of complications and marked decrease in radiation exposure. Although 3DI-only has some appeal, use of combined limited radiation is associated with some advantages overall. Potential adverse effects of limited radiation need to be weighed in when deciding which imaging or combination to use.
Molecular Imaging in Alzheimer’s Disease
Authors: Herholz Karl ,   Professor of Clinical Neuroscience, Wolfson Molecular Imaging Centre, University of Manchester
Published: October 2015

The most sensitive and accurate method for molecular imaging in human Alzheimer’s disease (AD) is positron emission tomography (PET). The most widely available PET tracer, which is also used in clinical oncology, is 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG is an imaging biomarker for early and differential diagnosis of AD. Even higher molecular specificity and sensitivity for detection of AD before dementia onset is provided by high-affinity ligands for fibrillary amyloid. 11C-Pittsburgh Compound B is widely being used in research laboratories, while new 18F-labelled ligands are currently undergoing formal clinical trials as amyloid imaging agents and are expected to become commercially available for clinical use in the near future. A large variety of tracers is being developed and used in dementia research for activated microglia and multiple neurotransmitter systems to study disease pathophysiology, biological correlates of clinical symptoms and new possibilities for treatment. Current studies in humans are investigating cholinergic, serotonergic and dopaminergic neurotransmission.
Update and Overview of the International League Against Epilepsy Consensus Definition of Drug-resistant Epilepsy
Authors: Hao Xiao-Ting , Kwan Patrick ,   Doctorate Student, Division of Neurology, Department of Neurology, West China Hospital, Sichuan University School of Medicine,   Associate Consultant, Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital
Published: October 2015

Drug-resistant epilepsy remains a major clinical challenge. Diverse criteria have been used to define drug resistance by different researchers, making it difficult or even impossible to compare the results across different studies. To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) recently proposed a consensus definition to define drug-resistant epilepsy. This is the failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This article outlines the framework of the consensus definition, explains how to apply it in practice and discusses the future development of its use.
Advances in Our Understanding of Dystonia - Pathophysiology and Treatment Options
Authors: Lubarr Naomi , Bressman Susan ,   Attending Neurologist, Division of Pediatric Neurology and Division of Movement Disorders, Department of Neurology, Beth Israel Medical Center,   Alan and Joan Mirken Chair, Department of Neurology, Beth Israel Medical Center and Professor of Neurology, Albert Einstein College of Medicine
Published: October 2015

Although the pathophysiology of dystonia remains incompletely understood, advances in two major areas of research over the past two decades have led to important insights into the mechanisms of dystonia. First, with the identification of dystonia genes, investigations using cellular and animal models of dystonia have become possible. Second, advances in functional neuroimaging have led to the possibility of identification of distinct functional, anatomical and neurochemical abnormalities in dystonia patients. Dystonia is currently conceptualised as a neurofunctional disorder characterised by alterations at various levels and multiple points along the sensorimotor circuit. There are multiple causes of these disruptions, and lesions along different points in interconnected pathways can yield similar motor dysfunction. The existence of dystonia endophenotypes in genetic forms of dystonia suggests that it may be a ‘second hit’ disorder, in which genetically predisposed brains can be thrown into an unbalanced dystonic state by environmental or genetic factors. Ultimately, a more complete understanding of the pathophysiology of dystonia should lead to better, more rational, targeted therapies.
Advances in the Role of Neuroimaging to Monitor Disease Progression in Parkinson’s Disease
Authors: Agarwal Pankaj A , Stoessl A Jon ,   Post-doctoral Fellow,   Director, Pacific Parkinson’s Research Centre, University of British Columbia and Vancouver Coastal Health
Published: October 2015

Since structural imaging has generally failed to demonstrate consistent abnormalities in Parkinson’s disease (PD), from an imaging perspective, the diagnosis has typically been based upon the demonstration of impaired striatal dopamine (DA) function. Radiotracer imaging techniques such as positron emission tomography (PET) and single photon emission computerised tomography (SPECT) allow thein vivoassessment of nigrostriatal DA function as well as regional cerebral blood flow, glucose metabolism, and functional connectivity, and changes in these measures have been used to infer disease progression. Pre-synaptic radiotracer imaging (RTI) has shown that striatal dopaminergic hypofunction follows a negative exponential pattern with the fastest rate of decline in early disease. Moreover, while striatal subregions remain differentially affected throughout the course of disease, with the posterior putamen affected more than anterior structures, the rate of deterioration is similar in all subregions. However, although functional imaging is undoubtedly a very useful tool in the assessment of PD progression, various studies have shown discordance between clinical progression of PD and nigrostriatal degeneration estimated by PET or SPECT. Therefore, considerable caution is warranted in the interpretation of imaging findings. While a potentially invaluable complement in assessing the severity of dopaminergic dysfunction, functional imaging is not a substitute for clinical assessment and other objective measures of PD severity, and cannot be currently considered a biomarker for progression of PD.
Surgical Management of Traumatic Brain Injury - Evidence, Controversies and Perspectives for the Future
Authors: Sener Süleyman , Roozenbeek Bob , Maas Andrew IR ,   Resident in Neurosurgery,   Resident in Neurosurgery,   Professor of Neurosurgery and Chairman, Department of Neurosurgery, Antwerp University Hospital
Published: October 2015

The surgical treatment of traumatic brain injury is challenging. Evidence-based recommendations provide guidance, but the underpinning evidence is relatively weak. This lack of strong evidence has been quoted to emphasise the need for more clinical trials. Clinical trials should, however, not be seen as the only approach. The existing variability in surgical management offers opportunities for comparative effectiveness research (CER) based upon large-scale observational studies. CER has the potential to provide high-quality evidence in a cost efficient way. Controversies are greatest concerning the surgical management of contusions and indications for decompressive craniectomy (DC). Lesion progression is frequent in contusions and mainly occurs within six–nine hours after injury. Surgical treatment can be motivated by both mass and toxic effects. On-going studies, such as the Surgical trial in traumatic intracerebral hemorrhage (STITCH), will hopefully provide further guidance on ‘best surgical approaches’. Currently, early computed tomography (CT) follow-up is recommended with surgical decisions based on CT evolution and risk assessment. The increasing enthusiasm for DC has been tempered by the results of the recent multicentre prospective randomised trial of early decompressive craniectomy in patients with severe traumatic brain injury (DECRA) study, showing more unfavourable outcome following DC. It is unlikely though that these results will change clinical practice, as the study population was highly selected and focused only on diffuse injuries. The results cannot be extrapolated to patients with focal or mass lesions. DC should not be considered a risk-free procedure. Complication rates of up to 50 % have been reported. Major complications include subdural effusions, hydrocephalus and syndrome of the trephined. Early cranioplasty is preferred following DC, as complications may resolve more rapidly and recovery is enhanced.
How Reversible are ‘˜Reversible Dementias’?
Authors: Ioannidis Panagiotis , Karacostas Dimitris ,   Lecturer in Neurology,   Associate Professor of Neurology, Department of Neurology, AHEPA University Hospital of Thessaloniki
Published: October 2015

Reversible dementias comprise different groups of disorders of variable aetiologies, such as structural brain lesions or metabolic, infectious, toxic, autoimmune, paraneoplastic and psychiatric disorders. When patients present with cognitive symptoms, especially in the younger age groups, the first thought of the attending neurologist should be to try to identify an underlying treatable cause. The incidence of degenerative dementia rises with older age and its symptoms progressively become more evident and typical; in such cases, a differential diagnosis is limited and the chance of uncovering a treatable disorder is minimal. However, although uncommon, treatable dementias or dementia-like symptoms do exist. Future studies with better design and methodology, as well as longer observation periods and larger patient populations, are needed to clarify the controversial issues concerning the epidemiology and accurate diagnosis of, and treatment possibilities for, reversible dementias.
Involvement of Nutrients in the Pathogenesis or Management of Alzheimer’s Disease
Authors: Wurtman Richard J ,   Cecil H Green Distinguished Professor Emeritus, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology
Published: October 2015

The number of hippocampal and cortical synapses is diminished in early Alzheimer’s disease (AD) and this loss, which is well correlated with the onset of cognitive deficits, probably reflects both an acceleration in their breakdown and a slowing in their synthesis, perhaps consequent to the concurrent decrease in dendritic spines. No strategies have been identified for increasing the number of synapses. Synaptogenesis requires adequate amounts of highly specialised synaptic membrane and activation of a process for shaping this membrane, initially into dendritic spines and neurites and then into the synapses themselves. Both can be enhanced by providing, concurrently, three circulating compounds present in the diet – uridine (as its monophosphate), docosahexaenoic acid (DHA) and choline – which can be rate-limiting precursors in membrane phosphatide synthesis. The uridine, as uridine triphosphate (UTP), also activates brain P2Y receptors, which facilitate neuronal differentiation and affect the production of synaptic proteins. In two large-scale clinical trials, patients with early AD who received the precursors and cofactors orally for up to 24 weeks exhibited significant improvements in memory indices.
3,4-diaminopyridine Phosphate in the Treatment of Lambert-Eaton Myasthenic Syndrome
Authors: Sieb Jörn Peter ,   Professor, Department of Neurology, Hanse-Klinikum Stralsund and University of Bonn
Published: October 2015

3,4-diaminopyridine (3,4-DAP, amifampridine) is the leading treatment for Lambert–Eaton myasthenic syndrome (LEMS), an autoimmune disorder with impaired neuromuscular transmission, for which few effective medications are currently available. 3,4-DAP has been available as a therapy for LEMS in special treatment programmes for approximately 25 years. As an unlicensed drug, doses for oral administration are required to be compounded by local, hospital or other compounding pharmacies from the base chemical. Administering the correct dose of 3,4-DAP is critical; overdosing can increase the risk of seizures and other adverse events, while underdosing can result in a substantial loss of efficacy or even treatment failure. Two recent studies, have shown a wide variation in the 3,4-DAP content of compounded preparations (22.2–125.2 %, n=9) and (53.5–128.5 %, n=21), thereby reflecting the possibility of patients receiving dosages that might be above safety limits or even markedly below efficacy limits. This inconsistency results from the variable quality and instability of the base chemical and compounding errors. A formulation of 3,4-DAP phosphate salt has now been licensed in Europe and the US with orphan medicinal product status and appears to be as efficacious as the base in relieving the symptoms of LEMS.
Management of Neuropathic Pain - Current Insights and Future Perspectives
Authors: Smith Howard S , Kara Sukriye Damla , Argoff Charles E ,   Professor and Academic Director of Pain Management, Department of Anesthesiology, Albany Medical College,   Undergraduate Student, University of Rochester,   Professor of Neurology and Director, Comprehensive Pain Center, Department of Neurology, Albany Medical College
Published: October 2015

The management of neuropathic pain remains very challenging and very much an art. Despite the publication of multiple consensus guidelines on the management of neuropathic pain, a significant subpopulation of patients with neuropathic pain are not afforded adequate relief, employing various treatment algorithms with conventional pharmacological therapeutic strategies. First-line agents for the treatment of neuropathic pain include: tricyclic antidepressants, selective serotonin/norepinephrine re-uptake inhibitors, calcium channel 〈2-δ ligands and, in certain cases of focal neuropathic pain, a lidocaine patch. Novel analgesics under development may include: purinergic receptor modulators, cannabinoid receptor modulators, neurokinin-1 (NK-1) receptor modulators, glial modulators, rostral ventral medulla ‘on-cell’ modulators, chemokine receptor modulators, toll-like receptor modulators, modulators of tetrahydrobiopterin synthesis and/or chemically re-engineered conotoxins. It is hoped that future agents and/or combinations of agents may be helpful to this refractory subpopulation.
Intra-operative Imaging Techniques During Surgical Management of Gliomas
Authors: Tarapore Phiroz E , Chang Edward F , Berger Mitchel S ,   Resident,   Assistant Professor of Neurological Surgery and Physiology,   Professor and Chairman, Department of Neurological Surgery, University of California, San Francisco
Published: October 2015

The goal of glioma surgery is to maximise tumour removal while preserving existing function. Intra-operative imaging techniques play an important part in achieving this goal. This article surveys those techniques and discusses the indications, advantages and drawbacks of each. Structural techniques such as intra-operative magnetic resonance imaging (MRI), ultrasound, diffusion tensor imaging and 5-aminolevulinic acid staining offer anatomical information. Functional techniques such as functional MRI, magnetoencephalography and transcranial magnetic stimulation provide information about the functionality of brain regions. When incorporated into a frameless stereotactical neuronavigation system, these modalities increase both the efficacy and safety of glioma surgery by allowing the surgeon to achieve the most extensive and safe resection possible.