bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisión conceptual de la conexión entre inteligencia emocional y autoconcepto físico
Authors: Zurita Ortega F. , Moreno Arrebola R. , González Valero G. , Viciana Garófano V. , Martínez Martínez A. , Muros Molina J. J.
Published: April 2018

En la actualidad el conocimiento de los aspectos físicos y cognitivos es esencial en el contexto deportivo, ante esta situación la imagen que tiene una persona sobre sí mismo (autoconcepto) y el cómo se encuentra emocionalmente (inteligencia emocional) repercute en la acción deportiva. Ante esta situación se plantea el siguiente trabajo con la intención de examinar el número de estudios que hay en la Web of Science que contengan los términos autoconcepto e inteligencia emocional junto con los parámetros actividad física y deporte, tanto en castellano como en inglés. Los resultados depararon que existía un mayor número de artículos en lengua inglesa que en castellano, asimismo los estudios relacionados con autoconcepto son más numerosos que los de inteligencia emocional, y cuando se buscan trabajos que contengan la totalidad de los parámetros antes citados, en castellano no se detectan trabajos, mientras que en inglés aparecen dieciséis.
Relación entre inversión y resultados deportivos de España y el Reino Unido en los últimos 20 años (1996-2016)
Authors: González-Ruiz J. , Torres-Luque G. , Roca-Cruz A. , Puga González E. , Cabello-Manrique D.
Published: April 2018

El objeto del estudio es analizar cómo los ciclos económicos afectan a la inversión en el tercer sector del deporte y a los resultados deportivos internacionales. Se comparan los modelos de España y Reino Unido. Se seleccionaron los resultados olímpicos de ambos países en los últimos 20 años (Sídney 2000; Atenas 2004; Pekín 2008; Londres 2012 y Río 2016). Los resultados muestran como España ha ido disminuyendo la inversión pública en deporte desde la crisis, pero ha logrado mantener sus resultados deportivos en los Juegos Olímpicos. Esto evidencia una posible mejora de los recursos públicos y de la generación de recursos propios. Reino Unido muestra una recuperación económica mucho más sólida, que ha potenciado sus resultados deportivos, casi doblando el número de medallas en el periodo poscrisis. Se constata una mayor eficacia y eficiencia del modelo de Reino Unido que necesita menos de la mitad de deportistas olímpicos para conseguir excelentes resultados, generando un coste de medalla por habitante un 50% menor que España.
Long-term Conventionally Dosed Vancomycin Therapy In Patients With Orthopaedic Implant-related Infections Seems As Effective And Safe As Long-term Penicillin Or Clindamycin Therapy. A Retrospective Cohort Study Of 103 Patients
Authors: Aleman Jacomien , F. Dirk Jan , van Marc L. , Poolman Rudolf W. , Franssen Eric J.F.
Published: April 2018

Abstract. Objectives: Antimicrobial therapy is one of the cornerstones of orthopaedic implant-related infections (OIRI) treatment. Infections with Gram-positive bacteria are often treated with vancomycin, penicillin or clindamycin. A recent IDSA guideline suggests increasing the dose of vancomycin to increase the trough vancomycin target serum concentrations. This is deemed necessary because of an observed decrease in vancomycin susceptibility among Gram-positive bacteria. However, elevated vancomycin concentrations are correlated with the risk of nephrotoxicity, especially with prolonged therapy. Compared to most countries, rates of resistance against antibiotics among bacteria in the Netherlands are lower for currently available antibiotics, therefore lower target concentrations of vancomycin are probably efficacious for the treatment of infections.In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, as an initial therapy for OIRI, and compared this with long-term penicillin and clindamycin therapy, as initial therapy, in patients with Gram-positive orthopaedic implant-related infections.Methods: A retrospective, observational study was conducted in 103 adult patients treated for OIRI, with vancomycin, penicillin or clindamycin for at least 10 days. The target trough serum concentration of vancomycin was 10-15 mg/l.Results: 74% of our patients were treated successfully with vancomycin, as initial therapy, (no reinfection within 1 year) versus 55% of our patients treated with either an antibiotic of the penicillin class (mostly flucloxacillin) or clindamycin (p=0.08), as initial therapy. For patients treated with vancomycin we observed a serum creatinine increase of 6 μmol/l, for patients treated with either an antibiotic of the penicillin class or clindamycin the serum creatinine increase was 4 μmol/l (p=0.395).Conclusions: In our population of patients with OIRI long-term treatment with conventionally dosed vancomycin, as initial therapy, was not significantly less effective and safe as long-term treatment with an antibiotic of the penicillin class or clindamycin, as initial therapy.
Effects of Local Application of Nano-silver on Osteomyelitis and Soft Tissue Infections: An Experimental Study in Rats
Authors: Kemah Bahattin , Uzer Gökçer , Turhan Yalçın , Özturan Burak , Kılıç Bülent , Gültepe Bilge Sümbül , Ceyran Ayşe Bahar , Ertürk Selim , Aksoylu Burak , Şenaydın Özlem , Özkan Korhan
Published: April 2018

Abstract. Purpose: Bone and soft tissue infections are among the least desired complications after orthopaedic surgery. This study analysed the in vivo effects of the local application of nano-silver particles (AgNPs) [1nm = 1 billionth of a meter] in soft tissue infections.Materials-Method: An experimental osteomyelitis model was formed by inoculating both tibias of 24 rats with methicillin-resistant Staphylococcus aureus. The rats were followed without treatment for 21 days. Blood samples and tibial x-rays at day 21 confirmed the development of infection. Then, the rats were divided randomly into two groups. One group (12 rats) underwent surgical debridement and received 21 days of teicoplanin therapy. The second group had the same treatment, with the addition of local nano-silver. All of the rats were sacrificed at day 42. Blood and wound swab samples were taken and the culture results were analysed.Results: No differences were observed between the groups in healing values at pathological examination, or in changes in the number of colonies at days 21 and 42. No differences in white blood cell count (WBC) were observed between the groups before and after the treatment.Conclusion: Although in vitro studies suggest the effectiveness of AgNPs on pathogens, we found that the application of nano-silver did not make any difference when used in addition to the classical osteomyelitis treatment with antibiotics and local surgical debridement. We believe that additional in vivo studies using repeated nano-silver application could be beneficial.
Case Report: Combining Dalfampridine with Multicomponent Exercise and Gait Training in a Person with Multiple Sclerosis
Authors: Plummer Prudence , Bohling Corinne J. , Nickles L. Ellese , Williams Alexis A. , Thomas Amy , Markovic-Plese Silva , Giesser Barbara
Published: April 2018

Background:

Dalfampridine extended release (D-ER) improves gait speed in some people with multiple sclerosis (MS), but many patients who take D-ER demonstrate only small improvements of questionable clinical significance. Physical therapy (PT) may augment the treatment effects of D-ER on the nervous system and improve clinical outcomes. This case report describes the successful use of D-ER combined with multicomponent PT in a patient who did not have a clinically important change in gait speed with D-ER alone.

Methods:

A 59-year-old woman with a 6-year history of relapsing-remitting MS was prescribed D-ER by her neurologist. After 3 weeks of D-ER therapy (10 mg twice daily), she demonstrated only a 7.1% improvement in the Timed 25-Foot Walk test. She then commenced PT consisting of two 40-minute sessions per week for 6 weeks while continuing D-ER therapy. Training focused on gait, balance, coordination, functional strengthening, and dual-task performance.

Results:

After 6 weeks of D-ER + PT, she had a further 14.6% improvement in Timed 25-Foot Walk gait speed, for a total improvement of 20.7%, which elevated her above the clinically meaningful threshold of 20%. Similar patterns of improvement were also observed for self-selected gait speed in single- and dual-task conditions. Improvements in fast and dual-task gait speed were retained 3 weeks later.

Conclusions:

For this patient, combining PT with D-ER therapy improved gait speed more than the use of D-ER alone. Further investigation of D-ER + PT or PT as an alternative to D-ER in patients with submeaningful medication response is warranted.
Visualization of Biomedical Data
Authors: O'Donoghue Seán I , Baldi Benedetta F , Clark Susan J , Darling Aaron E , Hogan James M , Kaur Sandeep , Maier-Hein Lena , McCarthy Davis J , Moore William J , Stenau Esther , Swedlow Jason R , Vuong Jenny , Procter James B
Published: April 2018

The rapid increase in volume and complexity of biomedical data requires changes in research, communication, training, and clinical practices. This includes learning how to effectively integrate automated analysis with high-data-density visualizations that clearly express complex phenomena. In this review, we summarize key principles and resources from data visualization research that address this difficult challenge. We then survey how visualization is being used in a selection of emerging biomedical research areas, including: 3D genomics, single-cell RNA-seq, the protein structure universe, phosphoproteomics, augmented-reality surgery, and metagenomics. While specific areas need highly tailored visualization tools, there are common visualization challenges that can be addressed with general methods and strategies. Unfortunately, poor visualization practices are also common; however, there are good prospects for improvements and innovations that will revolutionize how we see and think about our data. We outline initiatives aimed at fostering these improvements via better tools, peer-to-peer learning, and interdisciplinary collaboration with computer scientists, science communicators, and graphic designers.
Core Self-Evaluations and Innovative Behavior Among Microentrepreneurs: The Mediating Effect of Proactive Personality
Authors: Purba Debora Eflina , Paundra Joshua
Published: April 2018

Given the key role that entrepreneurs play in a country’s economic growth, there is a need to study how entrepreneurs innovate for their firm’s survival. This study aims to investigate the mediating effect of proactive personality on the relationship between core self-evaluations (CSE) and innovative behaviors among microentrepreneurs. Data was obtained from a survey administered to 307 micro entrepreneurs in Jakarta, Indonesia and its surrounding cities. Data was tested using Hayes’ PROCESS macro on SPSS. Results showed that proactive personality mediated the relationship between CSE and innovative behavior, whereby CSE leads to proactive personality, which in turn influences innovative behavior. Theoretical and practical implications of the findings are further discussed
Coordination of robust single cell rhythms in the Arabidopsis circadian clock via spatial waves of gene expression
Authors: Gould Peter D , Domijan Mirela , Greenwood Mark , Tokuda Isao T , Rees Hannah , Kozma-Bognar Laszlo , Hall Anthony JW , Locke James CW
Published: April 2018

The Arabidopsis circadian clock orchestrates gene regulation across the day/night cycle. Although a multiple feedback loop circuit has been shown to generate the 24-hr rhythm, it remains unclear how robust the clock is in individual cells, or how clock timing is coordinated across the plant. Here we examine clock activity at the single cell level across Arabidopsis seedlings over several days under constant environmental conditions. Our data reveal robust single cell oscillations, albeit desynchronised. In particular, we observe two waves of clock activity; one going down, and one up the root. We also find evidence of cell-to-cell coupling of the clock, especially in the root tip. A simple model shows that cell-to-cell coupling and our measured period differences between cells can generate the observed waves. Our results reveal the spatial structure of the plant clock and suggest that unlike the centralised mammalian clock, the Arabidopsis clock has multiple coordination points.
Large-scale two-photon imaging revealed super-sparse population codes in the V1 superficial layer of awake monkeys
Authors: Tang Shiming , Zhang Yimeng , Li Zhihao , Li Ming , Liu Fang , Jiang Hongfei , Lee Tai Sing
Published: April 2018

One general principle of sensory information processing is that the brain must optimize efficiency by reducing the number of neurons that process the same information. The sparseness of the sensory representations in a population of neurons reflects the efficiency of the neural code. Here, we employ large-scale two-photon calcium imaging to examine the responses of a large population of neurons within the superficial layers of area V1 with single-cell resolution, while simultaneously presenting a large set of natural visual stimuli, to provide the first direct measure of the population sparseness in awake primates. The results show that only 0.5% of neurons respond strongly to any given natural image — indicating a ten-fold increase in the inferred sparseness over previous measurements. These population activities are nevertheless necessary and sufficient to discriminate visual stimuli with high accuracy, suggesting that the neural code in the primary visual cortex is both super-sparse and highly efficient.
Avaliação de Riscos Aplicada à Conservação e Restauração do Patrimônio Industrial Móvel: O Rolo Compactador da Escola de Belas Artes, Universidade Federal de Minas Gerais – Brasil
Authors: Silva Ronaldo
Published: April 2018

Este artigo apresenta uma proposta de avaliação de riscos para a conservação de patrimônio industrial móvel segundo o modelo de gestão de riscos aplicado à conservação preventiva. O objeto de estudo consiste em um rolo compactador rodoviário a vapor alemão, da marca Schwartzkopff, que foi produzido em 1920 e utilizado durante as décadas 1940/1950 nas obras de implantação do Campus Pampulha da Universidade Federal de Minas Gerais (UFMG) em Belo Horizonte, Minas Gerais, Brasil. A metodologia de trabalho se baseia nos métodos do Instituto Canadense de Conservação (IIC) e do Instituto de Património Cul tu ral Espanhol (IPCE), com foco nos modelos de identificação de agentes de deterioração, de Michalski e de avaliação de riscos segundo o Método ABC (Michalski e Pedersoli Jr.). Busca-se assim propor reflexões acerca da preservação de elementos industriais como objetos patrimoniais não somente históricos, mas culturais e incluir a ciência e a tecnologia como fatores de representatividade e identidade de indivíduos, grupos e da sociedade.
Retouching glass plate negatives. What do old manuals say?
Authors: Pereira Catarina Cortes , Castro Laura
Published: April 2018

This paper aims to present a study of old photographic retouching manuals which is part of a research project on the retouching of gelatin silver glass plate negatives from Portuguese photographic collections from the first half of the twentieth century. Several contemporary authors of various nationalities were studied. Differences in approach to retouching have been explored in terms of techniques and materials, particularly as the authors addressed issues such as ethics and the legitimacy of photo retouching, as well as the relationship of photography to the other arts.
Antigas Impregnações a Óleo Aplicadas no Reverso de Pintura sobre Tela. O Estudo Científico dos Materiais Encontrados numa Pintura Portuguesa
Authors: Teixeira Andréa , Calvo Ana , Aguiar Maria
Published: April 2018

Testemunho de intervenções históricas de restauro, o suporte da pintura sobre tela “O Cavaleiro da Ordem de Malta”, datada do século XVIII, foi alvo da aplicação, pelo seu reverso, de camadas de impregnação à base de óleo e pigmentos. O estudo científico das camadas de impregnação, com o recurso à microscopia ótica (MO) de reflexão, com luz polarizada e com radiação ultravioleta (UV), cromatografia gasosa acoplada à espectrometria de massa (GC-MS), micro-espectroscopia de infravermelho com transformada de Fourier (micro-FTIR) e microscopia eletrónica de varrimento acoplada a espectrometria de raios X por dispersão de energia (SEM-EDX), possibilitou a identificação de duas camadas compostas por diversos pigmentos aglutinados em óleo de linhaça e ainda a presença de resina colofónia, cola animal e amido.
Four Reliquary Busts from the former Monastery of Madre de Deus: Study and Conservation
Authors: Cunha Diana , Barata Carolina , Pais Alexandre
Published: April 2018

This article describes the conservation and restoration treatments as well as the historical and analytical study carried out on four reliquary busts from the former Monastery of Madre de Deus, in Lisbon, currently the National Azulejo Museum. These reliquaries belong to a collection composed of forty-five reliquary busts, which represent a unique and practically intact set and has dated busts from the late 16th century until late 17th century. The analytical results obtained suggest that the four busts were produced according to the art treatises of the time and the identified materials meet the materials that would be used in that period.
A MATRIZ ENERGÉTICA BAIANA E O POTENCIAL DE APROVEITAMENTO SOLAR E EÓLICO NA GERAÇÃO DE ENERGIA ELÉTRICA NO ESTADO DA BAHIA
Authors: De Oliveira Thiago Figueiredo , De Souza Karina Barbosa , Rocha Neto João Florêncio , Couto Elizabeth Da Rocha
Published: April 2018

O presente estudo possui como objetivo norteador a avaliação do potencial de aproveitamento solar e eólico para a geração de energia elétrica no estado da Bahia, apresentando vantagens, desvantagens e um levantamento da estimativa de quanto poderia se acrescentar na composição da matriz energética estadual. Com o decorrer da pesquisa, foi observado um enorme potencial de aproveitamento solar e eólico para geração de eletricidade no Estado, no qual, atualmente, concentram-se investimentos significativos do setor, em que a região centro-oeste foi a que se apresentou como a mais promissora. Em contrapartida, ainda existem barreiras ao desevolvimento e disseminação de tais tecnologias, como problemas relacionados à falta de linhas de transmissão. Como base metodológica, foi realizada pesquisa e coleta de dados preferenciais em agências, associações e empresas atuantes no setor de energia, a exemplo de Agência Nacional de Energia Elétrica e Associações Brasileiras de Energia Eólica e de Energia Solar, visando-se sempre uma maior confiabilidade nas informações.
QUALIDADE DAS ÁGUAS DAS BACIAS HIDROGRÁFICAS DA CIDADE DE SALVADOR E DO MUNICÍPIO DE LAURO DE FREITAS, BAHIA
Authors: Santos Juliana Jesus , Junior Ailton Dos Santos , Pita Najara Santana , Conceição Emily Karle Dos Santos , Souza Valdinei Mauricio Batista , Faria Aiane Catarina Fernandes
Published: April 2018

Os rios urbanos são parte de um complexo sistema, um espelho socioambiental das cidades. Os impactos causados à qualidade ambiental das águas dos rios urbanos impedem que os mesmos desempenhem suas funções ambientais, sociais, culturais e religiosas. As influências humanas na qualidade e no funcionamento adequado/natural dos sistemas hídricos, em prol do desenvolvimento urbano, despontam como as grandes responsáveis pelas condições atuais de suas águas. O objetivo principal deste trabalho foi avaliar o estado geral da qualidade das águas das Bacias Hidrográficas das cidades de Salvador e Lauro de Freitas, no estado da BA, a partir de duas abordagens complementares: o uso do Índice de Qualidade das Águas da National Sanitation Foundation e o Índice de Estado Trófico. Para a avaliação, foram selecionados ao menos três pontos em cada um dos principais rios de cada bacia, resultando num total de 47 pontos. Os pontos escolhidos estão dispostos da seguinte forma: um próximo à nascente, um próximo à foz e os demais, a meio curso. Esse delineamento permite realizar o acompanhamento da qualidade ao longo do rio. Os resultados do Índice da Qualidade da Água (IQA) e do Índice de Estado Trófico (IET) apresentaram cenários distintos para as Bacias Hidrográficas analisadas. Foi possível diagnosticar a perda progressiva da qualidade das águas da nascente para a foz em razão do aporte de efluentes domésticos oriundos das regiões mais densamente habitadas. Neste sentido, 70% dos mananciais foram diagnosticados para a qualidade ambiental como Ruim ou Péssimo, de acordo com o IQA. Quanto ao IET, todos os pontos apresentaram algum nível de eutrofização, mesmo aqueles que apresentaram boa qualidade. A maior parte, quase 50% dos trechos avaliados, apresentou eutrofização num estágio avançado (supereutrófico e/ou hipereutrófico), comprometendo assim seus usos múltiplos.
Hacia un diseño de investigación académica en danza performance tecnológica

Authors: Ceriani Alejandra
Published: April 2018

Resumen

La investigación en Arte; y más específicamente, la investigación en Danza performances y Tecnologías de la Información y la Comunicación (TIC) -desde la academia  local-; es un asunto pendiente. Sus contenidos epistemológicos son aún discutibles, proviniendo durante los últimos años, tanto de las propias prácticas hibridas entre informáticos y artes escénicas (sobre todo referido a la producción de obra) como de políticas y estrategias educativas. Esto lo transforma en un argumento heterogéneo, lo que no siempre contribuye a la claridad del debate.

Lo esencial de la cuestión es si existe un fenómeno como la investigación transdisciplinar en danza performances y tecnología; según el cual el proceso de discrepancias metodológicas y materiales -entre lo corporal y lo puramente informático- es en sí mismo una parte primordial del resultado de dicha investigación. Y no, como ocurre generalmente, sea “la obra” el resultado “artístico” esperado. 

Palavras clave: Corpo. Dança performance tecnológica. Investigação acadêmica. Investigação em arte. Metodologias.

 

PARA UM PROJETO DE INVESTIGAÇÃO ACADÊMICA NA DANÇA PERFORMANCE TECNOLÓGICA

Resumo

Pesquisa em Arte, e mais especificamente, a pesquisa em performances de dança e tecnologias de informação e comunicação (TIC) - da academia local, é uma questão pendente. Os seus conteúdos epistemológicos que surgiram nos últimos anos, ainda são discutíveis tanto das práticas híbridas entre ciência da computação e as artes cênicas (principalmente referentes à produção de trabalho), quanto das políticas e estratégias educacionais. Isso o transforma em um argumento heterogêneo que nem sempre contribui para a clareza do debate.

A essência da questão é saber se existe um fenômeno como a pesquisa transdisciplinar em performances de dança e tecnologia segundo a qual o processo de discrepâncias metodológicas e materiais - entre o corpóreo e o puramente informatizado - é, por si só, uma parte primordial do resultado da referida investigação, e não, como costuma acontecer, o resultado “artístico” é “o trabalho” esperado.

Palavras-chave: Corpo. Dança desempenho tecnológico. Investigação académica. Investigação em arte. Metodologias.
Post-colonialism and performance: Political, cutural and pedagogic legacies and constraints
[Victor Ukaegbu]
Authors: Ukaegbu Victor
Published: April 2018

A maioria das sociedades pós-coloniais continuam a suportar as cicatrizes do colonialismo
europeu em seus domínios culturais, políticos e pedagógicos. Relacionamentos neocolonialistas
com seus antigos colonizadores continuam a afetar as condições históricas e materiais de cada
nação-estado pós-colonial na medida em que molda a sinergia entre os sistemas culturais de
indígenas e estrangeiros e como as sociedades pós coloniais modelam seus universos. Este ensaio
olha amplamente para o estado do pós-colonialismo no século XXI, argumenta que embora haja
oportunidades, a performance pós-colonial ainda está sujeita e restrições políticas, culturais e pegagógicas.
Memória visual do I Fórum Negro das Artes Cênicas
[Fabrícia Dias]
Authors: Dias Fabrícia
Published: April 2018

Realizado em fevereiro de 2017, o I Fórum Negro das Artes Cênicas (FNAC) fomentou discussões
e iniciativas no âmbito do ensino das artes cênicas, sobretudo no contexto de articulação da
Escola de Teatro e do Programa de Pós-graduação da Universidade Federal da Bahia (UFBA).
Desenvolveu atividades dedicadas à formação, promovendo mesas de discussão, conferências,
atividades culturais e debates importantes a partir de ateliês temáticos – os ateliês foram espaços
de diálogo em que se propusessem sugestivas de inserção de temáticas negras (estética, poética,
ensino) no currículo acadêmico e na práxis docente. Esta breve curadoria fotográfica, tecida
durante a realização do FNAC por fotógrafos colaboradores da cidade de Salvador, homenageia
e busca inscrever na memória esse momento marcante, no qual professores, estudantes, arteeducadores, artistas e coletivos engajados com as pautas negras no âmbito acadêmico e cultural se debruçaram a refletir e propor ações a serem implantadas no ensino superior, promovendo a visibilidade e representatividade de negros e negras pesquisadores e fazedores das artes cênicas, nos âmbitos regional, nacional e internacional.
Culturas negras, ensino, pesquisa e formação em artes cênicas. Uma reflexão.
[Evani Tavares Lima e Fabrícia Dias]
Authors: Lima Evani Tavares , Dias Fabrícia
Published: April 2018

A proposta desta fala em forma de entrevista é discorrer a respeito do pensamento estético
negro nas artes cênicas, culturas negras e ensino, suas contribuições e possibilidade a partir da
prática de uma docente, artista e pesquisadora Inaicyra Falcão. Esta também uma reflexão política
respeito de iniciativas como o I Fórum Negro das Artes Cênicas (FNAC). Os principais pontos
discutidos durantes as mesas do evento serão aqui retomados a título de reflexão, na perspectiva
da construção de metodologias pluriculturais para a formação e vivência da arte.
American College of Rheumatology Provisional Criteria for Global Flares in Childhood‐Onset Systemic Lupus Erythematosus
Authors: Brunner Hermine I. , Holland Michael , Beresford Michael W. , Ardoin Stacy P. , Appenzeller Simone , Silva Clovis A. , Flores Francisco , Goilav Beatrice , Wenderfer Scott E. , Levy Deborah M. , Ravelli Angelo , Khunchandani Raju , Avcin Tadej , Klein‐Gitelman Marisa S. , Feldman Brian M. , Ruperto Nicolino , Ying Jun ,   the PRCSG and PRINTO Investigators
Published: April 2018

Objective

To validate the preliminary criteria of global flare for childhood‐onset SLE (cSLE).

Methods

Pediatricians experienced in cSLE care (n = 268) rated unique patient profiles; results of standard cSLE laboratory testing and information about the cSLE flare descriptors were presented as follows: global assessment of patient well‐being, physician global assessment of disease activity (MD‐global), Disease Activity Index score, protein/creatinine ratio (PCR), and erythrocyte sedimentation rate (ESR). Using rater interpretation of the course of cSLE (baseline versus followup as the gold standard), performance (sensitivity, specificity, area under the receiver operating characteristic curve [AUC]) of the preliminary flare criteria was tested. An international consensus conference was held to rank the preliminary flare criteria as per the American College of Rheumatology recommendations and delineate threshold scores for minor, moderate, and major flares.

Results

The accuracy of the 2 highest‐ranked candidate criteria that consider absolute changes (∆) of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) or British Isles Lupus Assessment Group (BILAG) (numeric scoring: A = 12, B = 8, C = 1, and D/E = 0), MD‐global, PCR, and ESR were confirmed (both AUC >0.93). For the SLEDAI‐based criteria (0.5 × ∆SLEDAI + 0.45 × ∆PCR + 0.5 × ∆MD‐global + 0.02 × ∆ESR) flare scores ≥6.4/3.0/0.6 constituted major/moderate/minor flares, respectively. For the BILAG‐based algorithm (0.4 × ∆BILAG + 0.65 × ∆PCR + 0.5 × ∆MD‐global + 0.02 × ∆ESR) flare scores ≥7.4/3.7/2.2 delineated major/moderator/minor flares, respectively. These threshold values (SLEDAI, BILAG) were all >82% sensitive and specific for capturing flare severity.

Conclusion

Provisional criteria for global flares in cSLE are available to identify patients who experienced a flare. These criteria also allow for discrimination of the severity of cSLE exacerbations.
A Novel Method to Combine Assessment of Benefit and Harm: Outcome Measures in Rheumatology 3×3 Methodology Applied to Two Active Comparator Trials
Authors: Boers Maarten , Singh Jasvinder A. , Cofield Stacey S. , Bridges S. Louis , Moreland Larry W. , O'Dell James R. , Wu Hongsheng , Leatherman Sarah , Curtis Jeffrey R.
Published: April 2018

Objective

The Outcome Measures in Rheumatology (OMERACT) 3×3 method analyzes the occurrence of benefit and harm simultaneously at the individual patient level. We applied this method to 2 recent rheumatoid arthritis (RA) trial data sets.

Methods

The Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) and the Rheumatoid Arthritis Comparison of Active Therapies (RACAT) randomized trial outcomes for safety were defined according to OMERACT as having no adverse events (AEs), non‐serious AEs, and serious AEs. Treatment efficacy was defined as good, moderate, or no response. A good treatment response without any AEs was labeled an unqualified success, and no treatment response but at least 1 AE was considered an unmitigated failure. The association between benefit and harm was assessed by chi‐square or exact tests, as appropriate.

Results

In TEAR, 612 of 755 patients had response data at 48 weeks: 14% of patients experienced unqualified success and 9% had unmitigated failure, with no difference between the treatment arms. Treatment response and AE rates were not correlated. In RACAT, 309 of 353 patients had response data at 48 weeks: 6% of patients experienced unqualified success and 11% had unmitigated failure, with no differences between the treatment arms. Response and AE rates were negatively correlated. The frequency of AEs and serious AEs increased as response decreased (P = 0.008).

Conclusion

We found some evidence that clinical response may be reduced by the co‐occurrence of AEs.
Van Maldergem syndrome and Hennekam syndrome: Further delineation of allelic phenotypes
Authors: Ivanovski Ivan , Akbaroghli Susan , Pollazzon Marzia , Gelmini Chiara , Caraffi Stefano Giuseppe , Mansouri Mahboubeh , Chavoshzadeh Zahra , Rosato Simonetta , Polizzi Valeria , Gargano Giancarlo , Alders Marielle , Garavelli Livia , Hennekam Raoul C.
Published: April 2018

Biallelic variants in FAT4 are associated with the two disorders, Van Maldergem syndrome (VMS) (n = 11) and Hennekam syndrome (HS) (n= 40). Both conditions are characterized by a typical facial gestalt and mild to moderate intellectual disability, but differ in the occurrence of neonatal hypotonia and feeding problems, hearing loss, tracheal anomalies, and osteopenia in VMS, and lymphedema in HS. VMS can be caused by autosomal recessive variants in DCHS1 as well, and HS can also be caused by autosomal recessive variants in CCBE1 and ADAMTS3. Here we report two siblings with VMS and one girl with HS, all with FAT4 variants, and provide an overview of the clinical findings in all patients reported with FAT4 variants. Our comparison of the complete phenotypes of patients with VMS and HS indicates a resemblance of several signs, but differences in several other main signs and symptoms, each of marked importance for affected individuals.
LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency
Authors: Stowe Robert C. , Sun Qin , Elsea Sarah H. , Scaglia Fernando
Published: April 2018

Lipoic acid is an essential cofactor for the mitochondrial 2‐ketoacid dehydrogenase complexes and the glycine cleavage system. Lipoyltransferase 1 catalyzes the covalent attachment of lipoate to these enzyme systems. Pathogenic variants in LIPT1 gene have recently been described in four patients from three families, commonly presenting with severe lactic acidosis resulting in neonatal death and/or poor neurocognitive outcomes. We report a 2‐month‐old male with severe lactic acidosis, refractory status epilepticus, and brain imaging suggestive of Leigh disease. Exome sequencing implicated compound heterozygous LIPT1 pathogenic variants. We describe the fifth case of LIPT1 deficiency, whose phenotype progressed to that of an early infantile epileptic encephalopathy, which is novel compared to previously described patients whom we will review. Due to the significant biochemical and phenotypic overlap that LIPT1 deficiency and mitochondrial energy cofactor disorders have with pyruvate dehydrogenase deficiency and/or nonketotic hyperglycinemia, they are and have been presumptively under‐diagnosed without exome sequencing.
Identification of a novel homozygous ALX4 mutation in two unrelated patients with frontonasal dysplasia type‐2
Authors: El‐Ruby Mona , El‐Din Fayez Alaa , El‐Dessouky Sara H. , Aglan Mona S. , Mazen Inas , Ismail Nora , Afifi Hanan H. , Eid Maha M. , Mostafa Mostafa I. , Mehrez Mennat I. , Khalil Yasmin , Zaki Maha S. , Gaber Khaled R. , Abdel‐Hamid Mohamed S. , Abdel‐Salam Ghada M. H.
Published: April 2018

We report two unrelated boys with frontonasal dysplasias type‐2 (FND‐2) who shared an identical novel homozygous ALX4 mutation c.291delG (p.Q98Sfs*83). Both patients presented with a large skull defect but one had bilateral parietal meningocele‐like cysts that lie along with the bony defect and increased in size with age. Scalp alopecia, hypertelorism, and clefted alae nasi were also detected in both of them. Furthermore, impalpable gonads were noted, being unilateral in one and bilateral in the other. Neuroimaging showed small dysplastic occipital lobes with dysgyria and midline subarachnoid cyst. Additional dysplastic corpus callosum and small cerebellar vermis were observed in one patient. Parietal foramina were noted in the parents of one patient. Our findings highlight the dosage effect of ALX4 and underscore the challenges of prenatal genetic counseling. Further, the indirect role of ALX4 in the development of the occipital lobe and posterior fossa is discussed.
Functional mRNA analysis reveals aberrant splicing caused by novel intronic mutation in WDR45 in NBIA patient
Authors: Willoughby Josh , Duff‐Farrier Celia , Desurkar Archana , Kurian Manju , Raghavan Ashok ,   DDD Study, Balasubramanian Meena
Published: April 2018

WDR45 gene‐associated neurodegeneration with brain iron accumulation (NBIA), referred to as beta‐propeller protein‐associated neurodegeneration (BPAN), is a rare disorder that presents with a very nonspecific clinical phenotype in children constituting global developmental delay. This case report illustrates the power of a combination of trio exome sequencing, in silico splicing analysis, and mRNA analysis to provide sufficient evidence for pathogenicity of a relatively intronic variant in WDR45, and in so doing, find a genetic diagnosis for a 6‐year‐old patient with developmental delay and seizures, a diagnosis which may otherwise have only been found once the characteristic MRI patterns of the disease became more obvious in young adulthood.
A patient with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and severe hypoganglionosis associated with a novel SOX10 mutation
Authors: Akutsu Yuko , Shirai Kentaro , Takei Akira , Goto Yudai , Aoyama Tomohiro , Watanabe Akimitu , Imamura Masatoshi , Enokizono Takashi , Ohto Tatsuyuki , Hori Tetsuo , Suzuki Keiko , Hayashi Masaharu , Masumoto Kouji , Inoue Ken
Published: April 2018

In this report, we present the case of a female infant with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH) associated with a novel frameshift mutation (c.842dupT) in exon 5, the last exon of SOX10. She had severe hypoganglionosis in the small intestine and entire colon, and suffered from frequent enterocolitis. The persistence of ganglion cells made both the diagnosis and treatment difficult in the neonatal period. She also showed hypopigmentation of the irises, hair and skin, bilateral sensorineural deafness with hypoplastic inner year, severe demyelinating neuropathy with hypotonia, and diffuse brain hypomyelination. The p.Ser282GlnfsTer12 mutation presumably escapes from nonsense‐mediated decay and may generate a dominant‐negative effect. We suggest that hypoganglionosis can be a variant intestinal manifestation associated with PCWH and that hypoganglionosis and aganglionosis may share the same pathoetiological mechanism mediated by SOX10 mutations.
Autosomal recessive otofaciocervical syndrome type 2 with novel homozygous small insertion in PAX1 gene
Authors: Patil Siddaramappa Jagdish , Das Bhowmik Aneek , Bhat Venkatraman , Satidevi Vineeth Venugopal , Vasudevamurthy Rashmi , Dalal Ashwin
Published: April 2018

Otofaciocervical syndrome (OTFCS) is described as a single gene disorder of both autosomal dominant and autosomal recessive inheritance. The major clinical features of OTFCS include ear malformations (external/middle/inner ear), facial dysmorphism, shoulder girdle abnormalities, vertebral anomalies, and mild intellectual disability. The autosomal recessive form of OTFCS syndrome (OTFCS2) has been recently reported to be caused due to homozygous mutations in PAX1 gene. Here we report a third family of OTFCS2 phenotype wherein whole exome sequencing identified a novel homozygous small insertion in PAX1 as the underlying genetic cause.
Further delineation of achondroplasia–hypochondroplasia complex with long‐term survival
Authors: González‐del Angel Ariadna , Rius Rocío , Alcántara‐Ortigoza Miguel A. , Spector Elaine , del Castillo Victoria , Mata‐García Luis Enrique
Published: April 2018

Achondroplasia–hypochondroplasia (ACH–HCH) complex is caused by the presence of two different pathogenic variants in each allele of FGFR3 gene. Only four patients with confirmed molecular diagnoses have been reported to date, and the phenotype has not been fully defined. Here, we describe a Mexican patient with a confirmed molecular diagnosis of ACH–HCH complex. This patient exhibits intellectual disability, has a history of seizures, experienced multiple cardiorespiratory complications during early childhood, and required foramen magnum decompression. However, he now shows a stable health condition with long‐term survival (current age, 18 years). This case is particularly relevant to our understanding of ACH–HCH complex and for the genetic counseling of couples who are affected with ACH or HCH.
Genetic variation in biotransformation enzymes, air pollution exposures, and risk of spina bifida
Authors: Padula Amy M. , Yang Wei , Schultz Kathleen , Lee Cecilia , Lurmann Fred , Hammond S. Katharine , Shaw Gary M.
Published: April 2018

Spina bifida is a birth defect characterized by incomplete closure of the embryonic neural tube. Genetic factors as well as environmental factors have been observed to influence risks for spina bifida. Few studies have investigated possible gene‐environment interactions that could contribute to spina bifida risk. The aim of this study is to examine the interaction between gene variants in biotransformation enzyme pathways and ambient air pollution exposures and risk of spina bifida. We evaluated the role of air pollution exposure during pregnancy and gene variants of biotransformation enzymes from bloodspots and buccal cells in a California population‐based case‐control (86 cases of spina bifida and 208 non‐malformed controls) study. We considered race/ethnicity and folic acid vitamin use as potential effect modifiers and adjusted for those factors and smoking. We observed gene‐environment interactions between each of the five pollutants and several gene variants: NO (ABCC2), NO2 (ABCC2, SLC01B1), PM10 (ABCC2, CYP1A1, CYP2B6, CYP2C19, CYP2D6, NAT2, SLC01B1, SLC01B3), PM2.5 (CYP1A1 and CYP1A2). These analyses show positive interactions between air pollution exposure during early pregnancy and gene variants associated with metabolizing enzymes. These exploratory results suggest that some individuals based on their genetic background may be more susceptible to the adverse effects of pollution.
Two novel cases expanding the phenotype of SETD2‐related overgrowth syndrome
Authors: van Rij Maartje C. , Hollink Iris H. I. M. , Terhal Paulien Anna , Kant Sarina G. , Ruivenkamp Claudia , van Haeringen Arie , Kievit J. Anneke , van Belzen Martine J.
Published: April 2018

The SETD2‐related overgrowth syndrome is also called “Luscan‐Lumish syndrome” (OMIM 616831) with the clinical characteristics of intellectual disability, speech delay, macrocephaly, facial dysmorphism, and autism spectrum disorders. We report on two novel patients a 4.5‐year‐old boy and a 23‐year‐old female adolescent with a speech and language developmental delay, autism spectrum disorder and macrocephaly, who were both diagnosed with SETD2‐related overgrowth syndrome due to de novo frameshift mutations in the SETD2 gene. Features not previously described which were present in either one of our patients were nasal polyps, a large tongue with creases, a high pain threshold, constipation, and undescended testicles. These features may be related to the syndrome and may need special attention in future patients. Additionally, prevention of obesity should be an important point of attention for patients diagnosed with a SETD2‐related overgrowth syndrome.
Homozygous DMRT2 variant associates with severe rib malformations in a newborn
Authors: Bouman Arjan , Waisfisz Quinten , Admiraal Jop , van de Loo Moniek , van Rijn Rick R. , Micha Dimitra , Oostra Roelof‐Jan , Mathijssen Inge B.
Published: April 2018

Spondylocostal dysostosis (SCD) is a rare disorder characterized by vertebral segmentation defects and malformations of the ribs. SCD patients have some degree of (kypho)scoliosis, short stature and suffer from respiratory impairment due to the reduced size of their thoracic cage. Mutations in DLL3, MESP2, LFNG, HES7, TBX6, and RIPPLY2 are known to cause different subtypes of SCD. Here, we report on a male neonate with an apparent distinct SCD‐like phenotype only partly overlapping the previously described SCD subtypes. The proband presented with severe rib malformations (missing, fused, bifid, and hypoplastic ribs), vertebral malformations (intervertebral fusions of the laminae and irregular ossification of the vertebral bodies), and a mild scoliosis. Clear segmentation defects of the vertebral bodies were lacking. Other dysmorphic features were present as well. Severe respiratory insufficiency was present from birth. Whole exome sequencing identified a homozygous start‐loss variant in DMRT2 (NM_006557.6: c.1A > T p.[Met1?]) being a likely cause of the SCD‐like phenotype in the proband. Mutations in DMRT2 (OMIM#604935) have not been described in relation to SCD‐related phenotypes in humans before. However, Dmrt2 knock‐out mice exhibit severe rib and vertebral defects that strikingly overlap with the radiological phenotype of the proband reported here. Therefore, it seems plausible that mutations in DMRT2 are associated with a different (novel) subtype of SCD mainly characterized by severe rib anomalies but lacking clear segmentation defects of the vertebral bodies.
Williams–Beuren syndrome in diverse populations
Authors: Kruszka Paul , Porras Antonio R. , de Souza Deise Helena , Moresco Angélica , Huckstadt Victoria , Gill Ashleigh D. , Boyle Alec P. , Hu Tommy , Addissie Yonit A. , Mok Gary T. K. , Tekendo‐Ngongang Cedrik , Fieggen Karen , Prijoles Eloise J. , Tanpaiboon Pranoot , Honey Engela , Luk Ho‐Ming , Lo Ivan F. M. , Thong Meow‐Keong , Muthukumarasamy Premala , Jones Kelly L. , Belhassan Khadija , Ouldim Karim , El Bouchikhi Ihssane , Bouguenouch Laila , Shukla Anju , Girisha Katta M. , Sirisena Nirmala D. , Dissanayake Vajira H. W. , Paththinige C. Sampath , Mishra Rupesh , Kisling Monisha S. , Ferreira Carlos R. , de Herreros María Beatriz , Lee Ni‐Chung , Jamuar Saumya S. , Lai Angeline , Tan Ee Shien , Ying Lim Jiin , Wen‐Min Cham Breana , Gupta Neerja , Lotz‐Esquivel Stephanie , Badilla‐Porras Ramsés , Hussen Dalia Farouk , El Ruby Mona O. , Ashaat Engy A. , Patil Siddaramappa J. , Dowsett Leah , Eaton Alison , Innes A. Micheil , Shotelersuk Vorasuk , Badoe Ëben , Wonkam Ambroise , Obregon María Gabriela , Chung Brian H. Y. , Trubnykova Milana , La Serna Jorge , Gallardo Jugo Bertha Elena , Chávez Pastor Miguel , Abarca Barriga Hugo Hernán , Megarbane Andre , Kozel Beth A. , van Haelst Mieke M. , Stevenson Roger E. , Summar Marshall , Adeyemo A. Adebowale , Morris Colleen A. , Moretti‐Ferreira Danilo , Linguraru Marius George , Muenke Maximilian
Published: April 2018

Williams–Beuren syndrome (WBS) is a common microdeletion syndrome characterized by a 1.5Mb deletion in 7q11.23. The phenotype of WBS has been well described in populations of European descent with not as much attention given to other ethnicities. In this study, individuals with WBS from diverse populations were assessed clinically and by facial analysis technology. Clinical data and images from 137 individuals with WBS were found in 19 countries with an average age of 11 years and female gender of 45%. The most common clinical phenotype elements were periorbital fullness and intellectual disability which were present in greater than 90% of our cohort. Additionally, 75% or greater of all individuals with WBS had malar flattening, long philtrum, wide mouth, and small jaw. Using facial analysis technology, we compared 286 Asian, African, Caucasian, and Latin American individuals with WBS with 286 gender and age matched controls and found that the accuracy to discriminate between WBS and controls was 0.90 when the entire cohort was evaluated concurrently. The test accuracy of the facial recognition technology increased significantly when the cohort was analyzed by specific ethnic population (P‐value < 0.001 for all comparisons), with accuracies for Caucasian, African, Asian, and Latin American groups of 0.92, 0.96, 0.92, and 0.93, respectively. In summary, we present consistent clinical findings from global populations with WBS and demonstrate how facial analysis technology can support clinicians in making accurate WBS diagnoses.
Giant umbilical cord and hypoglycemia in an infant with Proteus syndrome
Authors: Saito Tomohiro , Nakane Takaya , Narusawa Munenori , Yagasaki Hideaki , Nemoto Atsushi , Naito Atsushi , Sugita Kanji
Published: April 2018

Proteus syndrome (PS) is characterized by the progressive, segmental, or patchy overgrowth of the skin, and other tissues. This is the first case report of recurrent severe insulin‐independent hypoglycemia in an infant with PS. Somatic p.E17K of AKT1 mutation was confirmed. The patient also had a giant umbilical cord, which has not yet been reported in PS.