Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial

BACKGROUND: Acute promyelocytic leukaemia is a chemotherapy-sensitive subgroup of acute myeloid leukaemia characterised by the presence of the PML-RARA fusion transcript. The present standard of care, chemotherapy and all-trans retinoic acid (ATRA), results in a high proportion of patients being cured. In this study, we compare a chemotherapy-free ATRA and arsenic trioxide treatment regimen with the standard chemotherapy-based regimen (ATRA and idarubicin) in both high-risk and low-risk patients with acute promyelocytic leukaemia.

METHODS: In the randomised, controlled, multicentre, AML17 trial, eligible patients (aged ≥16 years) with acute promyelocytic leukaemia, confirmed by the presence of the PML-RARA transcript and without significant cardiac or pulmonary comorbidities or active malignancy, and who were not pregnant or breastfeeding, were enrolled from 81 UK hospitals and randomised 1:1 to receive treatment with ATRA and arsenic trioxide or ATRA and idarubicin. ATRA was given to participants in both groups in a daily divided oral dose of 45 mg/m(2) until remission, or until day 60, and then in a 2 weeks on-2 weeks off schedule. In the ATRA and idarubicin group, idarubicin was given intravenously at 12 mg/m(2) on days 2, 4, 6, and 8 of course 1, and then at 5 mg/m(2) on days 1-4 of course 2; mitoxantrone at 10 mg/m(2) on days 1-4 of course 3, and idarubicin at 12 mg/m(2) on day 1 of the final (fourth) course. In the ATRA and arsenic trioxide group, arsenic trioxide was given intravenously at 0·3 mg/kg on days 1-5 of each course, and at 0·25 mg/kg twice weekly in weeks 2-8 of course 1 and weeks 2-4 of courses 2-5. High-risk patients (those presenting with a white blood cell count >10 × 10(9) cells per L) could receive an initial dose of the immunoconjugate gemtuzumab ozogamicin (6 mg/m(2) intravenously). Neither maintenance treatment nor CNS prophylaxis was given to patients in either group. All patients were monitored by real-time quantitative PCR. Allocation was by central computer minimisation, stratified by age, performance status, and de-novo versus secondary disease. The primary endpoint was quality of life on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 global health status. All analyses are by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN55675535.

FINDINGS: Between May 8, 2009, and Oct 3, 2013, 235 patients were enrolled and randomly assigned to ATRA and idarubicin (n=119) or ATRA and arsenic trioxide (n=116). Participants had a median age of 47 years (range 16-77; IQR 33-58) and included 57 high-risk patients. Quality of life did not differ significantly between the treatment groups (EORTC QLQ-C30 global functioning effect size 2·17 [95% CI -2·79 to 7·12; p=0·39]). Overall, 57 patients in the ATRA and idarubicin group and 40 patients in the ATRA and arsenic trioxide group reported grade 3-4 toxicities. After course 1 of treatment, grade 3-4 alopecia was reported in 23 (23%) of 98 patients in the ATRA and idarubicin group versus 5 (5%) of 95 in the ATRA and arsenic trioxide group, raised liver alanine transaminase in 11 (10%) of 108 versus 27 (25%) of 109, oral toxicity in 22 (19%) of 115 versus one (1%) of 109. After course 2 of treatment, grade 3-4 alopecia was reported in 25 (28%) of 89 patients in the ATRA and idarubicin group versus 2 (3%) of 77 in the ATRA and arsenic trioxide group; no other toxicities reached the 10% level. Patients in the ATRA and arsenic trioxide group had significantly less requirement for most aspects of supportive care than did those in the ATRA and idarubicin group.

INTERPRETATION: ATRA and arsenic trioxide is a feasible treatment in low-risk and high-risk patients with acute promyelocytic leukaemia, with a high cure rate and less relapse than, and survival not different to, ATRA and idarubicin, with a low incidence of liver toxicity. However, no improvement in quality of life was seen.

Understanding barriers to cataract surgery among older persons in rural China through focus groups.

PURPOSE: To utilize focus groups (FGs) to identify barriers to cataract surgery specific to older persons in rural Guangdong, China. METHODS: Three focus groups in separate locations were carried out for persons aged 60 years and above with best-corrected vision <= 6/18 due to cataract, either accepting or refusing surgery. Participants also ranked responses to questions about acceptance of surgery among the elderly. FG transcripts were coded independently by two investigators using qualitative data management software. RESULTS: Twenty participants had a mean age of 72.7 ± 6.1 years, 14 (70.0%) were women and 17 (85.0%) were blind (best-corrected vision <= 6/60) in at least one eye. Cost was ranked by two of three groups as the main barrier to surgery, and all groups listed reducing cost as the best strategy to increase surgical uptake. Many respondents planned to use China's New Cooperative Medical Scheme (NCMS) health insurance to pay for surgery. Participants showed poor understanding of cataract, but ranked educational interventions low as methods of increasing uptake. Though opinions of local service quality were poor, respondents did not see quality as an important barrier to accepting service. Participants frequently depended on family members to pay for surgery. CONCLUSIONS: Contrary to some previous reports, cost may be an important barrier to cataract surgery in rural China, which NCMS may help to alleviate. Educational interventions to increase knowledge about cataract are needed, but may face skepticism among patients. Strategies to promote cataract surgery should target the entire family.

Allocating Participants to Groups In Educational Trials: What Does Random Mean?

What is meant by the term random? Do we understand how to identify which type of randomisation to use in our future research projects? We, as researchers, often explain randomisation to potential research participants as being a 50/50 chance of selection to either an intervention or control group, akin to drawing numbers out of a hat. Is this an accurate explanation? And are all methods of randomisation equal? This paper aims to guide the researcher through the different techniques used to randomise participants with examples of how they can be used in educational research.

Magnitude differences in bioactive compounds, chemical functional groups, fatty acid profiles, nutrient degradation and digestion, molecular structure and metabolic characteristics of protein in newly developed yellow-seeded and black-seeded canola lines.

Recently, new lines of yellow-seeded (CS-Y) and black-seeded canola (CS-B) have been developed with chemical and structural alteration through modern breeding technology. However, no systematic study was found on the bioactive compounds, chemical functional groups, fatty acid profiles, inherent structure, nutrient degradation and absorption, or metabolic characteristics between the newly developed yellow- and black-seeded canola lines. This study aimed to systematically characterize chemical, structural, and nutritional features in these canola lines. The parameters accessed include bioactive compounds and antinutrition factors, chemical functional groups, detailed chemical and nutrient profiles, energy value, nutrient fractions, protein structure, degradation kinetics, intestinal digestion, true intestinal protein supply, and feed milk value. The results showed that the CS-Y line was lower (P ≤ 0.05) in neutral detergent fiber (122 vs 154 g/kg DM), acid detergent fiber (61 vs 99 g/kg DM), lignin (58 vs 77 g/kg DM), nonprotein nitrogen (56 vs 68 g/kg DM), and acid detergent insoluble protein (11 vs 35 g/kg DM) than the CS-B line. There was no difference in fatty acid profiles except C20:1 eicosenoic acid content (omega-9) which was in lower in the CS-Y line (P < 0.05) compared to the CS-B line. The glucosinolate compounds differed (P < 0.05) in terms of 4-pentenyl, phenylethyl, 3-CH3-indolyl, and 3-butenyl glucosinolates (2.9 vs 1.0 μmol/g) between the CS-Y and CS-B lines. For bioactive compounds, total polyphenols tended to be different (6.3 vs 7.2 g/kg DM), but there were no differences in erucic acid and condensed tannins with averages of 0.3 and 3.1 g/kg DM, respectively. When protein was portioned into five subfractions, significant differences were found in PA, PB1 (65 vs 79 g/kg CP), PB2, and PC fractions (10 vs 33 g/kg CP), indicating protein degradation and supply to small intestine differed between two new lines. In terms of protein structure spectral profile, there were no significant differences in functional groups of amides I and II, α helix, and β-sheet structure as well as their ratio between the two new lines, indicating no difference in protein structure makeup and conformation between the two lines. In terms of energy values, there were significant differences in total digestible nutrient (TDN; 149 vs 133 g/kg DM), metabolizable energy (ME; 58 vs 52 MJ/kg DM), and net energy for lactation (NEL; 42 vs 37 MJ/kg DM) between CS-Y and CS-B lines. For in situ rumen degradation kinetics, the two lines differed in soluble fraction (S; 284 vs 341 g/kg CP), potential degradation fraction (D; 672 vs 590 g/kg CP), and effective degraded organic matter (EDOM; 710 vs 684 g/kg OM), but no difference in degradation rate. CS-Y had higher digestibility of rumen bypass protein in the intestine than CS-B (566 vs 446 g/kg of RUP, P < 0.05). Modeling nutrient supply results showed that microbial protein synthesis (MCP; 148 vs 171 g/kg DM) and rumen protein degraded balance (DPB; 108 vs 127 g/kg DM) were lower in the CS-Y line, but there were no differences in total truly digested protein in small intestine (DVE) and feed milk value (FMV) between the two lines. In conclusion, the new yellow line had different nutritional, chemical, and structural features compared to the black line. CS-Y provided better nutrient utilization and availability.

High-order-harmonic generation in benzene with linearly and circularly polarised laser pulses

High-order-harmonic generation in benzene is studied using a mixed quantum-classical approach in which the electrons are described using time-dependent density functional theory while the ions move classically. The interaction with both linearly and circularly polarised infra-red ($\lambda = 800$ nm) laser pulses of duration 10 cycles (26.7 fs) is considered. The effect of allowing the ions to move is investigated as is the effect of including self-interaction corrections to the exchange-correlation functional. Our results for circularly polarised pulses are compared with previous calculations in which the ions were kept fixed and self-interaction corrections were not included while our results for linearly polarised pulses are compared with both previous calculations and experiment. We find that even for the short duration pulses considered here, the ionic motion greatly influences the harmonic spectra. While ionization and ionic displacements are greatest when linearly polarised pulses are used, the response to circularly polarised pulses is almost comparable, in agreement with previous experimental results.

Size Matters: The Effect of the Size of Ethnic Groups on Development

The share of ethnic groups is one of the most important features of African politics. It affects civil wars, representation in government positions, distributive and allocative policies. In this paper we use the partition of ethnic groups as a natural experiment in order to estimate the effect of the share of these ethnic groups on development. We show that larger groups have an advantage in terms of development and that the partition in itself does not matter for development. This result is explained by the fact that the partition matters only when the resulting groups are relatively small, since their lack of political representation may weaken support for institutions, may bias policies and the provision of ethnic/regional public goods.

Poly(vinyl alcohol) with sulfonic acid groups as catalyst for the alpha-pinene alkoxylation

The alkoxylation of a-pinene was carried out over poly(vinyl alcohol) containing sulfonic acid groups, as catalyst. The main product of a-pinene alkoxylation was a-terpinyl methyl ether being also formed bornyl methyl ether, fenchyl methyl ether, limonene and terpinolene as by-products. The absorption band at 1037 cm-1 in the FTIR spectrum of PVA_SSA40 (PVA membrane containing 40% of –OH groups esterified with SSA) which does not appear in the spectrum of PVA, indicates the presence of the sulfonic acid groups. The catalytic activity of PVA with sulfonic acid groups increases when the amount of sulfosuccinic acid used in the polymer crosslinking is increased from 5% to 40%. However, when the crosslinking degree increases from 20% to 40%, the conversion of a-pinene increases only slightly. Good values of selectivity to a-terpinyl methyl ether were obtained over poly(vinyl alcohol) with sulfonic acid groups. A simple kinetic model, which fits experimental concentration data quite well, was developed.

Revival: The Aesthetics of Revival Subcultures and Re-enactment Groups Explored Through Fashion Image-making

This research aims, through performance, fashion photography, video making and the theatrical devices that accompany such practice, to explore the style of a contemporary, largely male, subcultural collective. The common term that joins these loosely bound groups is revival as they appear driven by an impulse to simulate and re-enact the dress, rites and rituals of British and American subcultures from a perceived golden era. The similarities with re-enactment societies are also explored and exploited to the end of developing new style- based aesthetics in male fashion image-making formed around an elaborate re- enactment of Spartacus and the Third Servile Wars. Examined through comparative visuals (revivalists / re-enactors) a common thread is found in the wearing of leather as a metaphor for resistance, style and a pupa-like second skin. Subsequent findings of this research suggest that the cuirass of popular culture emerges as the motorcycle jacket of both the sword and sandal epic and the historical re-enactor. Addressing extremes in narcissistic dress and behaviour amongst certain individuals within these older male communities, this study also questions parts of established theory on subcultural development within the field of cultural studies and postulates on a metaphorical dandy gene. Citing two leading practitioners in the field of fashion photography the work of both Richard Prince and Bruce Weber is viewed through the lens of the subcultural aesthete and conclusions drawn as to their role as agents provocateurs in the development of the fashion image with a revival based narrative. In addition the often used term retro is examined, categorised and granted its own genre within fashion image- making and defined as being separate from the practice element of this research. Reflecting a multi-disciplinary approach that engages the researcher as Bricoleur and participant observer this research operates in the reflexive realm and uses simulation as a key method of enquiry. The practice-led outcome of this investigation takes the form of a final research exhibition that takes the form of a substantial installation of photography, video, clothing and textile prints. Key terms: dandy gene, historical re-enactment groups, internal theatre, narcissism, narrative image-making, reflexive practice, revival as theatre, subcultures,

Destructive Groups: The Role of Projective Identification in Suicidal Groups of Young People

Group suicidal behaviour by young people has been attracting increasing worldwide attention, but the subject has rarely been studied from a clinical or psychodynamic perspective. Although etiological factors are not well understood, unconscious as well as conscious group processes likely contribute to self-destructive actions. In this article we discuss the role of projective identification in the development of suicidal behavior by individuals who are part of a destructive group. We consider how these factors may operate, illustrated through a case description of a young man involved with a group of high school students that included at least four who made serious suicide attempts. Recognition and understanding of these forms of communication have important implications for clinical practice and suicide prevention.

Transportations of space, time and self: The role of therapeutic reading groups in managing mental distress in the community.

Background The practice of reading and discussing literature in groups is long established, stretching back into classical antiquity (Fischer, 2004). While benefits of therapeutic reading groups have been highlighted, research into participants’ perceptions of these groups has been limited (Walwyn & Rowley, 2011). Aims To explore the experiences of those attending therapeutic reading groups, considering the role of both the group, and the literature itself, in participants’ ongoing experiences of distress. Method Eleven participants were recruited from two reading groups in the South East of England. One focus group was run, and eight individuals self selected for individual interviews. The data were analysed together using a thematic analysis drawing on dialogical theories. Results Participants described the group as an anchor, which enabled them to use fiction to facilitate the discussion of difficult emotional topics, without referring directly to personal experience. Two aspects of this process are explored in detail: the use of narratives as transportation, helping to mitigate the intensity of distress; and using fiction to explore possibilities, alternative selves and lives. Conclusions For those who are interested and able, reading groups offer a relatively de-stigmatised route to exploring and mediating experiences of distress. Implications in the present UK funding environment are discussed.

Strategies of newsroom convergence: comparing UK and Chinese newspaper groups

This research examines media integration in China, choosing two Chinese newspaper groups as cases for comparative study. The study analyses the convergence strategies of these Chinese groups by reference to an Role Model of convergence developed from a literature review of studies of cases of media convergence in the UK – in particular the Guardian (GNM), Telegraph Media Group (TMG), the Daily Mail and the Times. UK cases serve to establish the characteristics, causes and consequences of different forms of convergence and formulate a model of convergence. The model will specify the levels of newsroom convergence and the sub-units of analysis which will be used to collect empirical data from Chinese News Organisations and compare their strategies, practices and results with the UK experience. The literature review shows that there is a need for more comparative studies of media convergence strategy in general, and particularly in relation to Chinese media. Therefore, the study will address a gap in the understanding of media convergence in China. For this reason, my innovations have three folds: Firstly, to develop a new and comprehensive model of media convergence and a detailed understanding of the reasons why media companies pursue differing strategies in managing convergence across a wide range of units of analysis. Secondly, this study tries to compare the multimedia strategies of media groups under radically different political systems. Since, there is no standard research method or systematic theoretical framework for the study of Newsroom Convergence, this study develops an integrated perspective. The research will use the triangulation analysis of textual, field observation and interviews to explain systematically what was the newsroom structure like in the past and how did the copy flow change and why. Finally, this case study of media groups can provide an industrial model or framework for the other media groups.

Working in and on groups: an illustration of the principles of exploratory practice in an esp classroom

Neste artigo, descrevo e analiso uma actividade de trabalho em grupo desenvolvida para uma aula da disciplina de Língua Inglesa VI das turmas do 3º ano do Curso de Línguas e Secretariado do Instituto Superior de Contabilidade e Administração do Porto (ISCAP). No enquadramento teórico, abordam-se questões relacionadas com o trabalho em grupo numa aula de língua estrangeira, nomeadamente a dimensão social da sala de aula em geral e da interacção aluno-aluno em particular. Apresentam-se então os princípios da Exploratory Practice, com ênfase na possibilidade preconizada por esta abordagem de se poder transformar uma actividade de reflexão e discussão sobre o processo de ensino/aprendizagem numa unidade pedagógica. Segue-se a apresentação da proposta didáctica, respectivo plano de aula e alguns exemplos dos textos produzidos pelos alunos. O artigo termina com a apresentação de alguns comentários críticos, realçando-se a contribuição da Exploratory Practice para o desenvolvimento de uma maior consciencialização por parte dos alunos do seu processo de aprendizagem.

Epidemiological studies of Streptococcus pneumoniae carriage in the post-vaccination era among two risk groups: children and the elderly

Dissertation presented to obtain the Ph.D. degree in Biology/ Molecular Biology

Portuguese business groups at the beginning of the 21st century: Trends, characteristics and configurations

This study considers the literature on the persistence of business groups in developed economies and analyzes the Portuguese case. The reconstruction of the largest business groups assembles information relevant to define characteristics that enable them to thrive. Increasing internationalization, more specialization in core activities and family control define these types of big businesses. New sectors also emerge as a characteristic of these business groups when compared to the ones existing 40 years ago.