Cross-sector surveys assessing perceptions of key stakeholders towards barriers, concerns and facilitators to the appropriate use of adaptive designs in confirmatory trials

Background Appropriately conducted adaptive designs (ADs) offer many potential advantages over conventional trials. They make better use of accruing data, potentially saving time, trial participants, and limited resources compared to conventional, fixed sample size designs. However, one can argue that ADs are not implemented as often as they should be, particularly in publicly funded confirmatory trials. This study explored barriers, concerns, and potential facilitators to the appropriate use of ADs in confirmatory trials among key stakeholders. Methods We conducted three cross-sectional, online parallel surveys between November 2014 and January 2015. The surveys were based upon findings drawn from in-depth interviews of key research stakeholders, predominantly in the UK, and targeted Clinical Trials Units (CTUs), public funders, and private sector organisations. Response rates were as follows: 30(55 %) UK CTUs, 17(68 %) private sector, and 86(41 %) public funders. A Rating Scale Model was used to rank barriers and concerns in order of perceived importance for prioritisation. Results Top-ranked barriers included the lack of bridge funding accessible to UK CTUs to support the design of ADs, limited practical implementation knowledge, preference for traditional mainstream designs, difficulties in marketing ADs to key stakeholders, time constraints to support ADs relative to competing priorities, lack of applied training, and insufficient access to case studies of undertaken ADs to facilitate practical learning and successful implementation. Associated practical complexities and inadequate data management infrastructure to support ADs were reported as more pronounced in the private sector. For funders of public research, the inadequate description of the rationale, scope, and decision-making criteria to guide the planned AD in grant proposals by researchers were all viewed as major obstacles. Conclusions There are still persistent and important perceptions of individual and organisational obstacles hampering the use of ADs in confirmatory trials research. Stakeholder perceptions about barriers are largely consistent across sectors, with a few exceptions that reflect differences in organisations’ funding structures, experiences and characterisation of study interventions. Most barriers appear connected to a lack of practical implementation knowledge and applied training, and limited access to case studies to facilitate practical learning. Keywords: Adaptive designs; flexible designs; barriers; surveys; confirmatory trials; Phase 3; clinical trials; early stopping; interim analyses

White youth: the Far Right, Punk and British youth culture

‘White Youth’ recovers and explains the relationship between far-right organisations and British youth culture in the period between 1977 and 1987. In particular, it concentrates on the cultural spaces opened up by punk and the attempts made by the National Front and British Movement to claim them as conduits for racist and/or ultra-nationalist politics. The article is built on an empirical basis, using archival material and a historical methodology chosen to develop a history ‘from below’ that takes due consideration of the socio-economic and political forces that inform its wider context. Its focus is designed to map shifting cultural and political influences across the far right, assessing the extent to which extremist organisations proved able to adopt or utilise youth cultural practice as a means of recruitment and communication. Today the British far right is in political and organisational disarray. Nonetheless, residues tied to the cultural initiatives devised in the 1970s–80s remain, be they stylistic, nostalgic or points of connection forged to connect a transnational music scene.

Civilian casualties – do we really care? The failure of the revolution in military affairs of non-lethal weapons in the U.S., Russia and Israel

Causing civilian casualties during military operations has become a much politicised topic in international relations since the Second World War. Since the last decade of the 20th century, different scholars and political analysts have claimed that human life is valued more and more among the general international community. This argument has led many researchers to assume that democratic culture and traditions, modern ethical and moral issues have created a desire for a world without war or, at least, a demand that contemporary armed conflicts, if unavoidable, at least have to be far less lethal forcing the military to seek new technologies that can minimise civilian casualties and collateral damage. Non-Lethal Weapons (NLW) – weapons that are intended to minimise civilian casualties and collateral damage – are based on the technology that, during the 1990s, was expected to revolutionise the conduct of warfare making it significantly less deadly. The rapid rise of interest in NLW, ignited by the American military twenty five years ago, sparked off an entirely new military, as well as an academic, discourse concerning their potential contribution to military success on the 21st century battlefields. It seems, however, that except for this debate, very little has been done within the military forces themselves. This research suggests that the roots of this situation are much deeper than the simple professional misconduct of the military establishment, or the poor political behaviour of political leaders, who had sent them to fight. Following the story of NLW in the U.S., Russia and Israel this research focuses on the political and cultural aspects that have been supposed to force the military organisations of these countries to adopt new technologies and operational and organisational concepts regarding NLW in an attempt to minimise enemy civilian casualties during their military operations. This research finds that while American, Russian and Israeli national characters are, undoubtedly, products of the unique historical experience of each one of these nations, all of three pay very little regard to foreigners’ lives. Moreover, while it is generally argued that the international political pressure is a crucial factor that leads to the significant reduction of harmed civilians and destroyed civilian infrastructure, the findings of this research suggest that the American, Russian and Israeli governments are well prepared and politically equipped to fend off international criticism. As the analyses of the American, Russian and Israeli cases reveal, the political-military leaderships of these countries have very little external or domestic reasons to minimise enemy civilian casualties through fundamental-revolutionary change in their conduct of war. In other words, this research finds that employment of NLW have failed because the political leadership asks the militaries to reduce the enemy civilian casualties to a politically acceptable level, rather than to the technologically possible minimum; as in the socio-cultural-political context of each country, support for the former appears to be significantly higher than for the latter.

Dietary Quality and Associated Factors among Factory Workers in the Metropolitan Region of Sao Paulo, Brazil

The workplace is a manageable community-based setting for ensuring proper nutrition. This study aimed to evaluate dietary quality and associated factors among adult workers at a cosmetics factory in the metropolitan area of Sao Paulo, Brazil. This factory was actively participating in the Brazilian Workers` Meal Program, which was created to ensure workers` nutritional health. In this cross-sectional study, data on 202 adult workers were assessed using questionnaires (sociodemographic, anthropometric, and lifestyle characteristics) administered during August and September 2006. Dietary intake, measured by 24-hour dietary recall, was used to calculate the modified Healthy Eating Index (HEI). A repeated administration of the 24-hour dietary recall was applied in a random subsample to calculate the modified HEI adjusted for the within-person variation in intake. Mean adjusted modified HEI scores were analyzed using multiple linear regression adjusted for energy. The mean adjusted modified HEI score was 72.3 +/- 8.0. The lowest adjusted modified HEI components scores were ""milk and dairy products"" (4.4 +/- 3.2) and ""sodium"" (3.7 +/- 3.1). Two percent of workers had ""poor diet"" (adjusted modified HEI score <51 points) and the majority (87%) had ""diet that needs modification"" (adjusted modified HEI score between 51 and 80), despite their participation in the meal program. Adjusted modified HEI scores were considerably higher for men (74.7 +/- 7.0) than for women (66.9 +/- 8.2) and for normal body mass index (calculated as kg/m(2)) (73.3 +/- 7.8) than for overweight/obese (70.9 +/- 8.1). Based on these results, the vast majority of workers were found to have diets that needed improvement. Individuals with higher-quality diets were more likely to have lower body mass index and to be male. J Am Diet Assoc. 2010;110:786-790.

Relationship between sleeping on the night shift and recovery from work among nursing workers - the influence of domestic work

P>Aim. This paper is a report of a study on the association between sleep patterns during work nights and recovery from work among nursing workers, considering domestic work hours. Background. Several hospitals allow nursing workers to sleep during the night shift, but this is rarely evaluated from the workers` health perspective. The need for recovery from work concept can be useful for testing the impact of night work on sleep. Recovery is not a problem if workers have enough time to recover between periods of work. Therefore, domestic work would be likely to interfere in the recovery process. Methods. This cross-sectional study was carried out at three hospitals in 2005-2006, through a comprehensive questionnaire. All nursing teams engaged in assistance to patients were invited to participate. Analyses included female night workers with no incidence of insomnia. Participants (n = 396) were classified into those who did not sleep during night shifts, those who slept for up to 2 hours and those who slept for 2-3 hours. Results. Binomial logistic regression analysis showed that sleeping on the job for 2-3 hours during night shifts is related to a better recovery from work provided the workers do not undergo long domestic work hours. Conclusions. Being allowed to sleep at work during night shifts seemed to contribute to, but was not enough to guarantee, a good recovery from work in the studied population. Recommendations to deal with sleep-deprivation among night workers should consider the complexity of gender roles on the recovery process.

Seasonality and growth rings in lianas of Bignoniaceae

Lianas are one of the most important components of tropical forest, and yet one of the most poorly known organisms. Therefore, our paper addresses questions on the environmental and developmental aspects that influence the growth of lianas of Bignoniaceae, tribe Bignonieae. In order to better understand their growth, we studied the stem anatomy, seasonality of formation and differentiation of secondary tissues, and the influence of the cambial variant in xylem development on a selected species: Tynanthus cognatus. Afterwards, we compared the results found in T. cognatus with 31 other species of Bignonieae to identify general patterns of growth in lianas of this tribe. We found that cambial activity starts toward the end of the rainy season and onset of the dry season, in contrast to what is known for tropical trees and shrubs. Moreover, their pattern of xylem formation and differentiation is strongly influenced by the presence of massive wedges of phloem produced by a variant cambium. Thus, the variant cambium is the first to commence its activity and only subsequently does cambial activity progress towards the center of the regular region, leading to the formation of confluent growth rings. In summary, we conclude that: the cambium responds to environmental changes; the xylem growth rings are annual and produced in a brief period of about 2 months, something that may explain why lianas possess narrow stems; and furthermore, phloem wedges greatly influence cambial activity.

An illustrated checklist of Bromeliaceae from Parque Estadual do Rio Preto, Minas Gerais, Brazil, with notes on phytogeography and one new species of Cryptanthus

A checklist of the 14 genera and 34 species of Bromeliaceae from the Parque Estadual do Rio Preto in Sao Goncalo do Rio Preto municipality, Minas Gerais state, southeastern Brazil, is presented. The Tillandsioideae was the most diverse subfamily and was found to be concentrated in rocky field areas. Bromelioideae is also a species rich subfamily, but its taxa have shown a preference to forested areas and savannas at lower altitudes. Pitcairnioideae is highlighted by its level of endemism, but has only four species. Cryptanthus micrus, a new species found in this area is described and illustrated. Our cluster analysis indicated that the Rio Preto State Park has a Bromeliaceae flora more similar to that from Pico do Itambe and Grao Mogol State Parks. Taxa like Dyckia glandulosa, Orthophytum itambense and Vriesea medusa, which were previously considered to be endemic to Pico do Itambe, now have their area of occurrence extended to Rio Preto. These new occurrences highlight the importance to create a corridor joining these neighboring reserves to connect populations of narrowly ranged or rare species. In this work we present pictures of 19 species in their habitats within the park, and we hope that these illustrations will help in the identification and conservation of these taxa.

Effects of let-7 microRNA on Cell Growth and Differentiation of Papillary Thyroid Cancer

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy and RET/PTC rearrangements represent key genetic events frequently associated to this cancer, enhancing proliferation and dedifferentiation by activation of the RET/PTC-RAS-BRAF-mitogen-activated protein kinase (MAPK) pathway. Recently, let-7 microRNA was found to reduce RAS levels in lung cancer, acting as a tumor suppressor gene. Here, we report that RET/PTC3 oncogenic activation in PCCL3 rat thyroid cells markedly reduces let-7f expression. Moreover, stable transfection of let-7 microRNA in TPC-1 cells, which harbor RET/PTC1 rearrangement, inhibits MAPK activation. As a result, let-7f was capable of reducing TPC-1 cell growth, and this might be explained, at least in part, by decreased messenger RNA (mRNA) expression of cell cycle stimulators such as MYC and CCND1 (cyclin D1) and increased P21 cell cycle inhibitor mRNA. In addition, let-7 enhanced transcriptional expression of molecular markers of thyroid differentiation such as TITF1 and TG. Thus, reduced expression of let-7f might be an essential molecular event in RET/PTC malignant transformation. Moreover, let-7f effects on thyroid growth and differentiation might attenuate neoplastic process of RET/PTC papillary thyroid oncogenesis through impairment of MAPK signaling pathway activation. This is the first functional demonstration of an association of let-7 with thyroid cancer cell growth and differentiation.

The role of glucocorticoid in SIRP alpha and SHP-1 gene expression in AIHA patients

The aim of this work was to evaluate the regulation of SIRP alpha, an inhibitory phagocyte receptor, and the phosphatase SHP-1 in monocytes of patients with autoimmune hemolytic anemia, and the role of dexamethasone on SIRP alpha and SHP-1 gene expression and erythrophagocytosis in vitro. SIRP alpha and SHP-1 expression was higher in monocytes from AIHA patients compared with normal, returning to normal after glucocorticoid therapy. SIRP alpha and SHP-1 mRNA expression was upregulated in healthy monocytes treated with dexamethasone compared with basal; however, the erythrophagocytic ability was not altered. Our results point to a minor role of SIRP alpha and SHP-1 in determining AIHA.

Mice and larvae tracking using a particle filter with an auto-adjustable observation model

This paper proposes a novel way to combine different observation models in a particle filter framework. This, so called, auto-adjustable observation model, enhance the particle filter accuracy when the tracked objects overlap without infringing a great runtime penalty to the whole tracking system. The approach has been tested under two important real world situations related to animal behavior: mice and larvae tracking. The proposal was compared to some state-of-art approaches and the results show, under the datasets tested, that a good trade-off between accuracy and runtime can be achieved using an auto-adjustable observation model. (C) 2009 Elsevier B.V. All rights reserved.

Chemoenzymatic synthesis of boron-containing chiral amines and amides

The first application of lipases as catalysts to obtain optically active boron-containing amines and amides is described. We studied several reaction conditions to achieve the kinetic resolution of boron-containing amines via enantioselective acylation mediated by Candida antarctica lipase B (CAL-B). Excellent enantioselectivity (E>200) and high enantiomeric excess (up to >99%) of both the remaining amines and amides were obtained. (C) 2010 Elsevier Ltd. All rights reserved.

Synthesis, Characterization, and Electrocatalytic Activity toward Methanol Oxidation of Carbon-Supported Pt(x)-(RuO(2)-M)(1-x) Composite Ternary Catalysts (M = CeO(2), MoO(3), or PbO(x))

Carbon-supported platinum is commonly used as an anode electrocatalyst in low-temperature fuel cells fueled with methanol. The cost of Pt and the limited world supply are significant barriers for the widespread use of this type of fuel cell. Moreover, Pt used as anode material is readily poisoned by carbon monoxide produced as a byproduct of the alcohol oxidation. Although improvements in the catalytic performance for methanol oxidation were attained using Pt-Ru alloys, the state-of-the-art Pt-Ru catalyst needs further improvement because of relatively low catalytic activity and the high cost of noble Pt and Ru. For these reasons, the development of highly efficient ternary platinum-based catalysts is an important challenge. Thus, various compositions of ternary Pt(x)-(RuO(2)-M)(1-x)/C composites (M = CeO(2), MoO(3), or PbO(x)) were developed and further investigated as catalysts for the methanol electro-oxidation reaction. The characterization carried out by X-ray diffraction, energy-dispersive X-ray analysis, transmission electron microscopy, X-ray photoelectron spectroscopy, and cyclic voltammetry point out that the different metallic oxides were successfully deposited on the Pt/C, producing small and well-controlled nanoparticles in the range of 2.8-4.2 nm. Electrochemical experiments demonstrated that the Pt(0.50)(RuO(2)-CeO(2))(0.50)/C composite displays the higher catalytic activity toward the methanol oxidation reaction (lowest onset potential of 207 mV and current densities taken at 450 mV, which are 140 times higher than those at commercial Pt/C), followed by the Pt(0.75)(RuO(2)-MoO(3))(0.25)/C composite. In addition, both of these composites produced low quantities of formic acid and formaldehyde when compared to a commercially available Pt(0.75)-Ru(0.25)/C composite (from E-Tek, Inc.), suggesting that the oxidation of methanol occurs mainly by a pathway that produces CO(2) forming the intermediary CO(ads).

The effect of social security, demography and technology on retirement

This article investigates the causes in the reduction of labor force participation of the old. We argue that the changes in social security policy, in technology and in demography may account for most of the changes in retirement over the second part of the last century in the U.S. economy. We develop a dynamic general equilibrium model with endogenous retirement that embeds social security legislation. The model is able to match very closely the increase in the retirement rate of males aged 65 and older. It also quanti es the isolated impact on retirement and on the solvency of the social security system of the di¤erent factors. The model suggests that technological and demographic changes had a strong in uence on retirement, so that it would have increased signi cantly even if the social security rules had not changed. However, as the latter became much more generous in the past, changes in social security policy can account not only for a sizeable part of the expansion of retirement, but also for the most of the observed increase in the social security expenses as a share of GDP.

Tecnologia e competitividade no Brasil - exploração integrada visando reconhecer os efeitos da introdução de novas tecnologias sobre a competitividade das empresas no contexto brasileiro

Esta pesquisa investiga as relações, nem sempre claras e explícitas, entre competitividade e inovação tecnológica, iniciando pelo referencial teórico. São estudados quatro casos de empresas, sendo três delas brasileiras e uma multinacional, dos setores de indústria e serviços. Dentre as conclusões, destaca-se a constatação de que a competitividade resulta da combinação de três dimensões: tecnologia, gestão (isto é, estratégia de negócio) e pessoas. Também se identificou uma íntima ligação entre inovação tecnológica e ganhos de market share. O estudo demonstra ainda que ganhos de competitividade com base tecnológica, ainda que significativos, são efêmeros, ou seja: a manutenção da vantagem competitiva é um processo dinâmico que exige permanentes esforços de inovação, inclusive com monitoramento constante do mercado e da concorrência. Outro aspecto investigado é o risco inerente à inovação, uma vez que o pioneirismo nem sempre encontra, de imediato, as soluções que se firmam como padrão no mercado. Finalmente, discorre-se também sobre o processo de decisão quanto a investimentos em tecnologia, apresentando modelos não quantitativos como auxiliares na análise e priorização de projetos inovadores.

Influência do desenvolvimento tecnológico sobre o desenvolvimento social a partir das atividades da incubadora tecnológica de Campina Grande, Campina Grande Paraíba

Este estudo avalia a influência do desenvolvimento tecnológico sobre o social, a partir das atividades produtivas desenvolvidas na unidade agroindustrial Recanto lI, no município de Catolé do Rocha, com o apoio da Incubadora Tecnológica de Campina Grande - ITCG, e o Programa de Estudos e Ações no Semi-Árido Paraibano da Universidade Federal de Campina Grande - PEASAlUFCG. Os problemas sociais no semi-árido surgiram por condições ambientais adversas e se intensificaram pela falta de políticas públicas adequadas à educação e ao desenvolvimento da região. O problema é expresso pela seguinte indagação: Qual a influência entre o desenvolvimento tecnológico e o desenvolvimento social gerados a partir da atividade produtiva da Incubadora de Campina Grande, em Campina Grande, Paraíba? A relevância deste trabalho vem da pretensão em colaborar para o estudo da relação entre desenvolvimento tecnológico e social, numa tentativa de tornar inteligível a necessidade de educação e inovação tecnológica para o desenvolvimento social, principalmente em países não desenvolvidos. Vem também da utilidade para a formulação de políticas públicas e estratégias de desenvolvimento tecnológico, identificando ações e medidas de desempenho, voltadas ao diagnóstico da contribuição das incubadoras tecnológicas para o bem-estar da sociedade. O referencial teórico foi composto pela análise da função das racionalidades dos diversos agentes sociais e de sua contribuição para as interações sociais, além da análise das realidades culturais da sociedade empresariada, do Estado e das incubadoras tecnológicas. A metodologia se utilizou da pesquisa descritiva e explicativa, de campo, documental, bibliográfica e estudo de caso. O universo foram as pessoas que compõem a ITCG e a amostra foram o diretor da Incubadora, o cientista da UFCG e o líder comunitário de Recanto lI. Os sujeitos da pesquisa confundem-se com a amostra. A coleta de dados se deu por meio da literatura sobre a temática e de inserções no campo de estudo. O tratamento de dados se utilizou da análise qualitativa do fenômeno. As principais limitações do método consistiram na coleta, no tratamento dos dados, e na utilização do estudo de caso, com possibilidade de compreensão tendenciosa do fenômeno estudado. O referencial prático apresenta o resultados da pesquisa, avaliando-os por meio da comparação com o referencial teórico estudado. Tem-se como resultados que a ITCG agiu articulando os grupos e traduzindo as realidades culturais de cada agente em prol do desenvolvimento de comunidades agroindustriais em situação de risco social, devido à problemática da seca. A ITCG atuou como alfabetizadora social ensinando aos agentes sociais os códigos culturais dos demais grupos. As desigualdades que existiam entre o cientista e o sertanejo, aprofundadas pelo vexatório histórico de escravidão do homem do campo no nordeste brasileiro, foram minimizadas pela educação dada pelo próprio cientista. A Universidade contribuiu para a redução do analfabetismo ambiental, onde o meio ambiente era tido como o principal rival do homem do sertão. O Estado, quando atua em parceria com os demais agentes sociais consegue, manter-se como o principal instrumento dos cidadãos para controlar a globalização em função de seus valores e interesses. Na ITCG o ambiente de incubação é educacional, onde os novos empreendedores são postos em contato com a realidade cultural do empresariado, do Estado e de outras comunidades da sociedade, seguindo modelos meramente educacionais. Como conclusão tem-se que a trajetória dos cidadãos de Recanto II - de escravos a exportadores - foi baseada em dois grandes tesouros, a família e areligião. O mérito da ITCG foi compreender, respeitar e preservar a realidade cultural de Recanto 11 e incentivar a interação social com outras realidades culturais capazes de gerar desenvolvimento naquela região. A saúde, o desenvolvimento infantil, a segurança, a habitação foram conquistas de Recanto 11. Como sugestão tem-se que as políticas públicas deveriam reproduzir este ambiente de desenvolvimento para todos os cidadãos brasileiros em situação de risco social, utilizando-se da família como base para interações sociais fluidas e harmônicas entre os diversos agentes sociais.