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Abstract: CXC chemokine receptor 4 (CXCR4) is overexpressed by a broad range of hematological disorders, and its interaction with CXC chemokine ligand 12 (CXCL12) is of central importance in the retention and chemoprotection of neoplastic cells in the bone marrow and lymphoid organs. In this article, we describe the biological evaluation of a new CXCR4-targeting and -antagonizing molecule (BAT1) that we designed and show that, when incorporated into a liposomal drug delivery system, it can be used to deliver cancer therapeutics at high levels to chronic lymphocytic leukemia (CLL) cells. CXCR4 targeting and antagonism by BAT1 were demonstrated alone and following its incorporation into liposomes (BAT1-liposomes). Antagonism of BAT1 against the CXCR4/CXCL12 interaction was demonstrated through signaling inhibition and function blocking: BAT1 reduced ERK phosphorylation and cell migration to levels equivalent to those seen in the absence of CXCL12 stimulation (P < .001). Specific uptake of BAT1-liposomes and delivery of a therapeutic cargo to the cell nucleus was seen within 3 hours of incubation and induced significantly more CLL cell death after 24 hours than control liposomes (P = .004). The BAT1 drug-delivery system is modular, versatile, and highly clinically relevant, incorporating elements of proven clinical efficacy. The combined capabilities to block CXCL12-induced migration and intracellular signaling while simultaneously delivering therapeutic cargo mean that the BAT1-liposome drug-delivery system could be a timely and relevant treatment of a range of hematological disorders, particularly because the therapeutic cargo can be tailored to the disease being treated.

BackgroundThe recognition and interpretation of abnormal blood cell morphology is often the first step in diagnosing underlying serious systemic illness or leukemia. Supporting the staff who interpret blood film morphology is therefore essential for a safe laboratory service. This paper describes an open-access, web-based decision support tool, developed by the authors to support morphological diagnosis, arising from earlier studies identifying mechanisms of error in blood film reporting. The effectiveness of this intervention was assessed using the unique resource offered by the online digital morphology Continuing Professional Development scheme (DM scheme) offered by the UK National External Quality Assessment Service for Haematology, with more than 3000 registered users. This allowed the effectiveness of decision support to be tested within a defined user group, each of whom viewed and interpreted the morphology of identical digital blood films. ObjectiveThe primary objective of the study was to test the effectiveness of the decision support system in supporting users to identify and interpret abnormal morphological features. The secondary objective was to determine the pattern and frequency of use of the system for different case types, and to determine how users perceived the support in terms of their confidence in decision-making. MethodsThis was a comparative study of identical blood films evaluated either with or without decision support. Selected earlier cases from the DM scheme were rereleased as new cases but with decision support made available; this allowed a comparison of data sets for identical cases with or without decision support. To address the primary objectives, the study used quantitative evaluation and statistical comparisons of the identification and interpretation of morphological features between the two different case releases. To address the secondary objective, the use of decision support was assessed using web analytical tools, while a questionnaire was used to assess user perceptions of the system. ResultsCases evaluated with the aid of decision support had significantly improved accuracy of identification for relevant morphological features (mean improvement 9.8%) and the interpretation of those features (mean improvement 11%). The improvement was particularly significant for cases with higher complexity or for rarer diagnoses. Analysis of website usage demonstrated a high frequency of access for web pages relevant to each case (mean 9298 for each case, range 2661-24,276). Users reported that the decision support website increased their confidence for feature identification (4.8/5) and interpretation (4.3/5), both within the context of training (4.6/5) and also in their wider laboratory practice (4.4/5). ConclusionsThe findings of this study demonstrate that directed online decision support for blood morphology evaluation improves accuracy and confidence in the context of educational evaluation of digital films, with effectiveness potentially extending to wider laboratory use.

Background: Diet plays a major role in cardiovascular disease (CVD) risk. Objectives: To determine the effectiveness of a Mediterranean-style diet for the primary and secondary prevention of CVD. Methods: We searched for randomised controlled trials (RCTs) of Mediterranean-style diets in healthy adults and those at increased risk of CVD (primary prevention) and with established CVD (secondary prevention). Results: Thirty RCTs were included, 22 in primary prevention and eight in secondary prevention. Clinical endpoints were reported in two trials where there was moderate quality evidence for a reduction in strokes for primary prevention, and low quality evidence for a reduction in total and CVD mortality in secondary prevention. We found moderate quality evidence of improvement in CVD risk factors for primary prevention and low quality evidence of little or no effect in secondary prevention. Conclusions: There is still some uncertainty regarding the effects of a Mediterranean-style diet in CVD prevention.

Background: Intensive care treatment can be life-saving, but it is invasive and distressing for patients receiving it and it is not always successful. Deciding whether or not a patient will benefit from intensive care is a difficult clinical and ethical challenge. Objectives: To explore the decision-making process for referral and admission to the intensive care unit and to develop and test an intervention to improve it. Methods: A mixed-methods study comprising (1) two systematic reviews investigating the factors associated with decisions to admit patients to the intensive care unit and the experiences of clinicians, patients and families; (2) observation of decisions and interviews with intensive care unit doctors, referring doctors, and patients and families in six NHS trusts in the Midlands, UK; (3) a choice experiment survey distributed to UK intensive care unit consultants and critical care outreach nurses, eliciting their preferences for factors used in decision-making for intensive care unit admission; (4) development of a decision-support intervention informed by the previous work streams, including an ethical framework for decision-making and supporting referral and decision-support forms and patient and family information leaflets. Implementation feasibility was tested in three NHS trusts; (5) development and testing of a tool to evaluate the ethical quality of decision-making related to intensive care unit admission, based on the assessment of patient records. The tool was tested for inter-rater and intersite reliability in 120 patient records. Results: Influences on decision-making identified in the systematic review and ethnographic study included age, presence of chronic illness, functional status, presence of a do not attempt cardiopulmonary resuscitation order, referring specialty, referrer seniority and intensive care unit bed availability. Intensive care unit doctors used a gestalt assessment of the patient when making decisions. The choice experiment showed that age was the most important factor in consultants’ and critical care outreach nurses’ preferences for admission. The ethnographic study illuminated the complexity of the decision-making process, and the importance of interprofessional relationships and good communication between teams and with patients and families. Doctors found it difficult to articulate and balance the benefits and burdens of intensive care unit treatment for a patient. There was low uptake of the decision-support intervention, although doctors who used it noted that it improved articulation of reasons for decisions and communication with patients. Limitations: Limitations existed in each of the component studies; for example, we had difficulty recruiting patients and families in our qualitative work. However, the project benefited from a mixed-method approach that mitigated the potential limitations of the component studies. Conclusions: Decision-making surrounding referral and admission to the intensive care unit is complex. This study has provided evidence and resources to help clinicians and organisations aiming to improve the decision-making for and, ultimately, the care of critically ill patients. Future work: Further research is needed into decision-making practices, particularly in how best to engage with patients and families during the decision process. The development and evaluation of training for clinicians involved in these decisions should be a priority for future work. Study registration: The systematic reviews of this study are registered as PROSPERO CRD42016039054, CRD42015019711 and CRD42015019714. Funding: The National Institute for Health Research Health Services and Delivery Research programme. The University of Aberdeen and the Chief Scientist Office of the Scottish Government Health and Social Care Directorates fund the Health Economics Research Unit.

INTRODUCTION:The view that interacting with nature enhances mental wellbeing is commonplace, despite a dearth of evidence or even agreed definitions of 'nature'. The aim of this review was to systematically appraise the evidence for associations between greenspace and mental wellbeing, stratified by the different ways in which greenspace has been conceptualised in quantitative research. METHODS:We undertook a comprehensive database search and thorough screening of articles which included a measure of greenspace and validated mental wellbeing tool, to capture aspects of hedonic and/or eudaimonic wellbeing. Quality and risk of bias in research were assessed to create grades of evidence. We undertook detailed narrative synthesis of the 50 studies which met the review inclusion criteria, as methodological heterogeneity precluded meta-analysis. RESULTS:Results of a quality assessment and narrative synthesis suggest associations between different greenspace characteristics and mental wellbeing. We identified six ways in which greenspace was conceptualised and measured: (i) amount of local-area greenspace; (ii) greenspace type; (iii) visits to greenspace; (iv) views of greenspace; (v) greenspace accessibility; and (vi) self-reported connection to nature. There was adequate evidence for associations between the amount of local-area greenspace and life satisfaction (hedonic wellbeing), but not personal flourishing (eudaimonic wellbeing). Evidence for associations between mental wellbeing and visits to greenspace, accessibility, and types of greenspace was limited. There was inadequate evidence for associations with views of greenspace and connectedness to nature. Several studies reported variation in associations between greenspace and wellbeing by life course stage, gender, levels of physically activity or attitudes to nature. CONCLUSIONS:Greenspace has positive associations with mental wellbeing (particularly hedonic wellbeing), but the evidence is not currently sufficient or specific enough to guide planning decisions. Further studies are needed, based on dynamic measures of greenspace, reflecting access and uses of greenspace, and measures of both eudaimonic and hedonic mental wellbeing.

ABSTRACTBACKGROUND: This is an update of the original review published in 2008. The risk of adverse cardiovascular outcomes is increased with influenza-like infection, and vaccination against influenza may improve cardiovascular outcomes.OBJECTIVES: To assess the potential benefits of influenza vaccination for primary and secondary prevention of cardiovascular disease.METHODS:Search methods:We searched the following electronic databases on 18 October 2013: The Cochrane Library (including Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Economic Evaluation Database (EED) and Health Technology Assessment database (HTA)), MEDLINE, EMBASE, Science Citation Index Expanded, Conference Proceedings Citation Index - Science and ongoing trials registers (www.controlled-trials.com/ and www.clinicaltrials.gov). We examined reference lists of relevant primary studies and systematic reviews. We performed a limited PubMed search on 20 February 2015, just before publication.Selection criteria:Randomised controlled trials (RCTs) of influenza vaccination compared with placebo or no treatment in participants with or without cardiovascular disease, assessing cardiovascular death or non-fatal cardiovascular events.Data collection and analysis:We used standard methodological procedures as expected by The Cochrane Collaboration. We carried out meta-analyses only for cardiovascular death, as other outcomes were reported too infrequently. We expressed effect sizes as risk ratios (RRs), and we used random-effects models.MAIN RESULTS: We included eight trials of influenza vaccination compared with placebo or no vaccination, with 12,029 participants receiving at least one vaccination or control treatment. We included six new studies (n = 11,251), in addition to the two included in the previous version of the review. Four of these trials (n = 10,347) focused on prevention of influenza in the general or elderly population and reported cardiovascular outcomes among their safety analyses; four trials (n = 1682) focused on prevention of cardiovascular events in patients with established coronary heart disease. These populations were analysed separately. Follow-up continued between 42 days and one year. Five RCTs showed deficits in at least three of the risk of bias criteria assessed. When reported (seven studies), vaccination provided adequate immunogenicity or protection against influenza. Cardiovascular mortality was reported by four secondary prevention trials and was significantly reduced by influenza vaccination overall (risk ratio (RR) 0.45, 95% confidence interval (CI) 0.26 to 0.76; P value 0.003) with no significant heterogeneity between studies, and by three trials reporting cardiovascular mortality as part of their safety analyses when the numbers of events were too small to permit conclusions. In studies of patients with coronary heart disease, composite outcomes of cardiovascular events tended to be decreased with influenza vaccination compared with placebo. Generally no significant difference was found between comparison groups regarding individual outcomes such as myocardial infarction.AUTHORS' CONCLUSIONS: In patients with cardiovascular disease, influenza vaccination may reduce cardiovascular mortality and combined cardiovascular events. However, studies had some risk of bias, and results were not always consistent, so additional higher-quality evidence is necessary to confirm these findings. Not enough evidence was available to establish whether influenza vaccination has a role to play in the primary prevention of cardiovascular disease.

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Sameness and difference across two nations and languages. In order to begin the discussion regarding a sitcom from American television used in a Brazilian classroom, I believe it is necessary to discuss the situation of the world as we know it at the beginning of the 21st century. Using the theories of the Brazilian sociologist Renato Ortiz (1994) as the basis for this discussion, it is possible to differentiate between the terms global and world-systemic (or mundial). In this view, global refers to the economic and technological processes at work in the modern day world, while world-systemic refers to the domain of culture. The category world is linked to the global, but signifies a world-view, a symbolic universe which is specific to the historic moment in which we live. [ABSTRACT FROM AUTHOR]

Background. Secondary prevention of coronary heart disease (CHD) among older individuals is associated with considerable benefit.Methods. In this study, we have examined the extent of secondary prevention among British women and men aged 60–79 years who were surveyed and examined between 1998 and 2001.Results. Among 483 women (12.1% of the whole sample) and 831 men (19.5%) with CHD, >90% of both sexes had at least one modifiable risk factor, with over two-fifths having high blood pressure and over three-quarters high cholesterol. For total cholesterol and body mass index, mean values in both male and female subjects were above recommended levels, and a large shift in the population distributions would be required for targets to be met. Less than one-quarter of subjects of either sex were on a statin, and whilst the majority of men were taking an antiplatelet medication, only 40% of women were.Conclusions. Most older women and men in Britain were failing to meet National Service Framework standards for secondary prevention in the period immediately before its implementation. Large shifts in the population distributions of some risk factors would be required in this group to meet these standards. [ABSTRACT FROM AUTHOR]

This article presents activities in which texts from children’s literature are used in English language teaching (ELT) in Brazil. These activities were used in classes of differing age levels and in two different types of school setting. Critical interculturality and languaculture are first presented as the theoretical basis of our pedagogical practice. Following the theory, three different activities using texts from children’s literature are then presented, demonstrating how texts such as these can aid in the teaching of an additional language. The first two activities were undertaken in a public school with young learners, the third activity was implemented in a language centre with adult students. Through these activities, the students were able to increase their grammatical and lexical knowledge of the English language as well as to interact with the languacultures of the texts. In this way, the English language classroom becomes an interculturally critical space in which learners can recreate their understanding of the target language.

En este artículo se analizan cuatro de doce mensajes reenviables, es decir, correos elec- trónicos recibidos durante un período de cuatro meses, con el objetivo de compren- der los discursos sobre los docentes y la profesión docente que prevalecen en el espacio cultural de los profesores en Brasil. Para analizar estos mensajes reenviados, combinamos el concepto de ámbito cultu - ral (Spradley, 1980) con los principios me - todológicos del análisis crítico del discurso (Fairclough, 2010). Nuestro análisis mues - tra otro aspecto de la identidad de grupo, además del relacionado con las actividades profesionales, que tiene que ver con la sen - sación de ocupar un lugar de bajo prestigio social. Los mensajes, por tanto, al ser envia - dos de maestro a maestro en una cadena continua se convierten en una forma de cohesión social de este grupo en particular.

O objetivo deste artigo é apresentar e analisar uma aula de língua inglesa que usou um tema polêmico, "Begging", do livro, Taboos and Issues, como base da discussão desenvolvida em sala de aula de língua inglesa. A pesquisa da qual este artigo faz parte é um estudo de caso de cunho etnográfico. Em primeiro lugar, foram levantados os domínios culturais que os autores do livro didático, do qual o tema foi retirado, usam para defender o uso de temas polêmicos em sala. Em seguida, as afirmações dos alunos sobre o assunto foram analisadas por meio do levantamento dos domínios culturais. A complexidade dos discursos que fluem em sala de aula e as rupturas que ocorrem são mostrados bem como a necessidade de o professor estar preparado para lidar com estes momentos.

O artigo que aqui apresentamos é uma tradução do texto originalde Karen Ann Watson-Gegeo, Ethnography in ESL: defining theEssentials, que tem por objetivo delinear os princípios essenciais dapesquisa etnográfica. Publicado em 1988 no TESOL Quarterly eposteriormente em 1995 na coletânea Readings on Second LanguageAcquisition, organizada por H. Douglas Brown e Susan T. Gonzo, oartigo destaca-se por apontar, de maneira sucinta e objetiva, uma opçãometodológica bastante adequada para as pesquisas em sala de aula desegunda língua/língua estrangeira, uma linha de pesquisa em expansãono nosso Programa de Pós-Graduação. Esperamos que a tradução dessetexto possa não só iluminar os caminhos dos nossos alunos pesquisadoresiniciantes, mas também dar visibilidade a uma abordagem de pesquisaque tem sido muitas vezes negligenciada entre os nossos pares.

Este artigo discute os conceitos relativos à pesquisa qualitativa em termos de paradigma, considerando a ontologia, a epistemologia e a metodologia dessa linha teórica. Em seguida, considera a etnografia, fazendo algumas sugestões sobre o seu uso nas pesquisas da linguística aplicada e enfocando especificamente as pesquisas de ensino–aprendizagem de segunda língua.PALAVRAS-CHAVE: pesquisa qualitativa, etnografia, linguística aplicada.

Resumo O presente artigo visa analisar o diálogo intercultural que ocorre em uma sala de aula de língua inglesa de uma escola pública da Rede Municipal de Ensino de Goiânia, capital do Estado de Goiás. Por se tratar de um estudo de cunho etnográfico, foram utilizadas as seguintes técnicas de geração de dados: a observação-participante, anotações de campo e gravações em vídeo. A partir desses instrumentos, procuramos, por meio da análise dos domínios culturais sugerida por Spradley (1980), interpretar os sentidos e os valores que os participantes atribuem às suas ações e às ações dos outros, como questionam seus papéis sociais e interpretam valores macroculturais de acordo com a sua própria microcultura. A análise dos dados demonstrou que o diálogo intercultural entre professora e alunos ocorre via embates. Também foi possível identificar os diferentes significados culturais que a sala de aula tem para a professora e para os alunos. Palavras-chave: interculturalidade – macro e microculturas – etnografia – inglês- escola pública Abstract This article discusses the intercultural dialogue between an English teacher and her students from a public school in Goiânia. It is a qualitative study based on ethnography in which the following instruments of generating data were used: participant observation, field notes and video recording. All the data are discussed following the ethnographic research directions and the domain analyses theory suggested by Spradley (1980). Through the cultural domains, it was possible to identify how the participants interpret theirs and others’ actions, how they question their social roles and interpret some macrocultural values according to their own microculture. The data analyses demonstrated how the intercultural dialogue between the teacher and her students is conflicted. In addition, it was possible to identify the different cultural meanings teacher and students give to the classroom. Keywords: intercultural dialogue – macro and microcultures - ethnography – English – public school

This article aims at identifying the school staff’s conceptions about integral education and fulltime schooling from a public school in Goiânia. It is a qualitative study based on ethnography in which the following instruments of generating data were used: participant observation, field notes, interviews, and the official documents that discuss integral education and fulltime schooling in Brazil and in Goiânia. The cultural domains analysis, suggested by Spradley (1980), revealed that the fulltime schooling model has not been well planned and established in our public schools, undermining the integral education effectiveness in these educational institutions

O presente artigo visa analisar as concepções dos integrantes do corpo docente e administrativo de uma escola pública do município de Goiânia a respeito de educação integral e tempo integral. Trata-se de um estudo qualitativo de cunho etnográfico no qual foram utilizados os seguintes instrumentos de geração de dados: observação-participante, entrevistas, anotações de campo e leitura dos documentos oficiais que legislam sobre a educação integral e tempo integral no Brasil e no município de Goiânia. A análise dos domínios culturais, sugerida por Spradley (1980), revelou que o tempo integral não tem chegado às nossas escolas públicas de maneira planejada, prejudicando, assim, a efetivação da educação integral nessas instituições de ensino.

This article focuses on a Canadian poetry course that was offered in the undergraduate English language course at Universidade Federal de Goiás, pointing out the factors that were taken into consideration to formulate the course program. In the second part of the article, a reading produced by the students of a poem by the Modernist poet Margaret Avison (Avison, 2005) is presented and discussed showing the strong points and the difficulties they had in its construction. The students’ opinions are analyzed using Gadamer’s (2000) philosophical hermeneutics in terms of the cultural horizon in which the poem was written and the cultural horizon of the students reading the poem focusing on the familiar and the strange. The contrast between referential texts and representational texts suggested by Widdowson (1992) is also focused on.

O presente artigo apresenta os conceitos de avaliação contidos na Lei de Diretrizes e Bases (LDB) e nos Parâmetros Curriculares Nacionais (PCN), para então examinar como dois professores da rede pública municipal da cidade de Goiânia conceituam o seu trabalho quanto à avaliação e como esses conceitos coadunam com a LDB e com os PCN.

Background: Exercise interventions are often incompletely described in reports of clinical trials, hampering evaluation of results and replication and implementation into practice., Objective: The aim of this study was to develop a standardized method for reporting exercise programs in clinical trials: the Consensus on Exercise Reporting Template (CERT)., Design and Methods: Using the EQUATOR Network's methodological framework, 137 exercise experts were invited to participate in a Delphi consensus study. A list of 41 items was identified from a meta-epidemiologic study of 73 systematic reviews of exercise. For each item, participants indicated agreement on an 11-point rating scale. Consensus for item inclusion was defined a priori as greater than 70% agreement of respondents rating an item 7 or above. Three sequential rounds of anonymous online questionnaires and a Delphi workshop were used., Results: There were 57 (response rate=42%), 54 (response rate=95%), and 49 (response rate=91%) respondents to rounds 1 through 3, respectively, from 11 countries and a range of disciplines. In round 1, 2 items were excluded; 24 items reached consensus for inclusion (8 items accepted in original format), and 16 items were revised in response to participant suggestions. Of 14 items in round 2, 3 were excluded, 11 reached consensus for inclusion (4 items accepted in original format), and 7 were reworded. Sixteen items were included in round 3, and all items reached greater than 70% consensus for inclusion., Limitations: The views of included Delphi panelists may differ from those of experts who declined participation and may not fully represent the views of all exercise experts., Conclusions: The CERT, a 16-item checklist developed by an international panel of exercise experts, is designed to improve the reporting of exercise programs in all evaluative study designs and contains 7 categories: materials, provider, delivery, location, dosage, tailoring, and compliance. The CERT will encourage transparency, improve trial interpretation and replication, and facilitate implementation of effective exercise interventions into practice., (© 2016 American Physical Therapy Association.)