Cyclin A/CDK2 regulates multiple G2 phase pathways

The cell cycle is a carefully choreographed series of phases that when executed successfully will allow the complete replication of the genome and the equal division of the genome and other cellular content into two independent daughter cells. The inability of the cell to execute cell division successfully can result in either checkpoint activation to allow repair and/or apoptosis and/or mutations/errors that may or may not lead to tumourgenesis. Cyclin A/CDK2 is the primary cyclin/CDK regulating G2 phase progression of the cell cycle. Cyclin A/CDK2 activity peaks in G2 phase and its inhibition causes a G2 phase delay that we have termed 'the cyclin A/CDK2 dependent G2 delay'. Understanding the key pathways that are involved in the cyclin A/CDK2 dependent G2 delay has been the primary focus of this study. Characterising the cyclin A/CDK2 dependent G2 delay revealed accumulated levels of the inactive form of the mitotic regulator, cyclin B/CDK1. Surprisingly, there was also increased microtubule nucleation at the centrosomes, and the centrosomes stained for markers of cyclin B/CDK1 activity. Both microtubule nucleation at the centrosomes and phosphoprotein markers were lost with short-term treatment of CDK1/2 inhibition. Cyclin A/CDK2 localised at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Thus G2 phase cyclin A/CDK2 controls the timing of entry into mitosis by controlling the subsequent activation of cyclin B/CDK1, but also has an unexpected role in coordinating the activation of cyclin B/CDK1 at the centrosome and in the nucleus. In addition to regulating the timing of cyclin B/CDK1 activation and entry into mitosis in the unperturbed cell cycle, cyclin A/CDK2 also was shown to have a role in G2 phase checkpoint recovery. Known G2 phase regulators were investigated to determine whether they had a role in imposing the cyclin A/ CDK2 dependent G2 delay. Examination of the critical G2 checkpoint arrest protein, Chk1, which also has a role during unperturbed G2/M phases revealed the presence of activated Chk1 in G2 phase, in a range of cell lines. Activated Chk1 levels were shown to accumulate in cyclin A/CDK2 depleted/inhibited cells. Further investigations revealed that Chk1, but not Chk2, depletion could reverse the cyclin A/CDK2 dependent G2 delay. It was confirmed that the accumulative activation of Chk1 was not a consequence of DNA damage induced by cyclin A depletion. The potential of cyclin A/CDK2 to regulate Chk1 revealed that the inhibitory phosphorylations, Ser286 and Ser301, were not directly catalysed by cyclin A/CDK2 in G2 phase to regulate mitotic entry. It appeared that the ability of cyclin A/CDK2 to regulate cyclin B/CDK1 activation impacted cyclin B/CDK1s phosphorylation of Chk1 on Ser286 and Ser301, thereby contributing to the delay in G2/M phase progression. Chk1 inhibition/depletion partially abrogated the cyclin A/CDK2 dependent G2 delay, and was less effective in abrogating G2 phase checkpoint suggesting that other cyclin A/CDK2 dependent mechanisms contributed to these roles of cyclin A/CDK2. In an attempt to identify these other contributing factors another G2/M phase regulator known to be regulated by cyclin A/CDK2, Cdh1 and its substrates Plk1 and Claspin were examined. Cdh1 levels were reduced in cyclin A/CDK2 depleted/inhibited cells although this had little effect on Plk1, a known Cdh1 substrate. However, the level of another substrate, Claspin, was increased. Cdh1 depletion mimicked the effect of cyclin A depletion but to a weaker extent and was sufficient at increasing Claspin levels similar to the increase caused by cyclin A depletion. Co-depletion of cyclin A and Claspin blocked the accumulation of activated Chk1 normally seen with cyclin A depletion alone. However Claspin depletion alone did not reduce the cyclin A/CDK2 dependent G2 delay but this is likely to be a result of inhibition of S phase roles of Claspin. Together, these data suggest that cyclin A/CDK2 regulates a number of different mechanisms that contribute to G2/M phase progression. Here it has been demonstrated that in normal G2/M progression and possibly to a lesser extent in G2 phase checkpoint recovery, cyclin A/CDK2 regulates the level of Cdh1 which in turn affects at least one of its substrates, Claspin, and consequently results in the increased level of activated Chk1 observed. However, the involvement of Cdh1 and Claspin alone does not explain the G2 phase delay observed with cyclin A/CDK2 depletion/inhibition. It is likely that other mechanisms, possibly including cyclin A/CDK2 regulation of Wee1 and FoxM1, as reported by others, combine with the mechanism described here to regulate normal G2/M phase progression and G2 phase checkpoint recovery. These findings support the critical role for cyclin A/CDK2 in regulating progression into mitosis and suggest that upstream regulators of cyclin A/CDK2 activation will also be critical controllers of this cell cycle transition. The pathways that work to co-ordinate cell cycle progression are very intricate and deciphering these pathways, required for normal cell cycle progression, is key to understanding tumour development. By understanding cell cycle regulatory pathways it will allow the identification of the pathway/s and their mechanism/s that become affected in tumourgenesis. This will lead to the development of better targeted therapies, inferring better efficacy with fewer side effects than commonly seen with the use of traditional therapies, such as chemotherapy. Furthermore, this has the potential to positively impact the development of personalised medicines and the customisation of healthcare.

Middle schooling and scientific literacy : bringing the students to science

This study is about young adolescents' engagement in learning science. The middle years of schooling are critical in the development of students' interest and engagement with learning. Successful school experiences enhance dispositions towards a career related to those experiences. Poor experiences lead to negative attitudes and rejection of certain career pathways. At a time when students are becoming more aware, more independent and focused on peer relationships and social status, the high school environment in some circumstances offers more a content-centred curriculum that is less personally relevant to their lives than the social melee surrounding them. Science education can further exacerbate the situation by presenting abstract concepts that have limited contextual relevance and a seemingly difficult vocabulary that further alienates adolescents from the curriculum. In an attempt to reverse a perceived growing disinterest by students to science (Goodrum, Druhan & Abbs, 2011), a study was initiated based on a student-centred unit designed to enhance and sustain adolescent engagement in science. The premise of the study was that adolescent students are more responsive toward learning if they are given an appropriate learning environment that helps connect their learning with life beyond the school. The purpose of this study was to examine the experiences of young adolescents with the aim of transforming school learning in science into meaningful experiences that connected with their lives. Two areas were specifically canvassed and subsumed within the study to strengthen the design base. One area that of the middle schooling ideology, offered specific pedagogical approaches and a philosophical framework that could provide opportunities for reform. The other area, the construct of scientific literacy (OECD, 2007) as defined by Holbrook and Rannikmae, (2009) appeared to provide a sense of purpose for students to aim toward and value for becoming active citizens. The study reported here is a self-reflection of a teacher/researcher exploring practice and challenging existing approaches to the teaching of science in the middle years of schooling. The case study approach (Yin, 2003) was adopted to guide the design of the study. Over a 6-month period, the researcher, an experienced secondary-science teacher, designed, implemented and documented a range of student-centred pedagogical practices with a Year-7 secondary science class. Data for this case study included video recordings, journals, interviews and surveys of students. Both quantitative and qualitative data sources were employed in a partially mixed methods research approach (Leech & Onwuegbuzie, 2009) dominated by qualitative data with the concurrent collection of quantitative data to corroborate interpretations as a means of analysing and developing a model of the dynamic learning environment. The findings from the case study identified five propositions that became the basis for a model of a student-centred learning environment that was able to sustain student participation and thus engagement in science. The study suggested that adolescent student engagement can be promoted and sustained by providing a classroom climate that encourages and strengthens social interaction. Engagement in science can be enhanced by presenting developmentally appropriate challenges that require rigorous exploration of contextually relevant learning environments; supporting students to develop connections with a curriculum that aligns with their own experiences. By setting an environment empathetic to adolescent needs and understandings, students were able to actively explore phenomena collaboratively through developmentally appropriate experiences. A significant outcome of this study was the transformative experiences of an insider, the teacher as researcher, whose reflections provide an authentic model for reforming pedagogy. The model and theory presented became an adjunct to my repertoire for science teaching in the middle years of schooling. The study was rewarding in that it helped address a void in my understanding of middle years of schooling by prompting me to re-think the notion of adolescence in the context of the science classroom. This study is timely given the report "The Status and Quality of Year 11 and 12 Science in Australian Schools" (Goodrum, Druhan & Abbs, 2011) and national curricular changes that are being proposed for science (ACARA, 2009).

Industry-school partnerships : an ecological approach

Internationally, Industry-School Partnerships (ISPs) are a ubiquitous government approach for enabling school to work transitions. Significant benefits of ISPs for centralised bureaucracies that are seeking to address common educational problems include: i) cost reduction; ii) supply to geographically dispersed locations, and; iii) industry access to innovative education solutions. In Queensland, there exists a government led ISP, the Gateway to Industry Schools Program. Under this initiative is the Queensland Minerals and Energy Academy, a lead industry organisation for 34 schools and 17 multinational sponsor companies. Acquiring an understanding of this strategic ISP is critical, given the current Resources Industry boom, and the workforce skills shortage experienced in Australia. This review paper adopts Ecological Systems Theory as a lens to understand the inner workings of ISPs. Acknowledging that ISPs will remain a key feature of government policy, this paper seeks to further illuminate the role of ISPs in transitioning young people from school to the working world.

Food in an Australian primary school curriculum : a critical sociological study

Food is a multidimensional construct. It has social, cultural, economic, psychological, emotional, biological, and political dimensions. It is both a material object and a catalyst for a range of social and cultural action. Richly implicated in the social and cultural milieu, food is a central marker of culture and society. Yet little is known about the messages and knowledges in the school curriculum about food. Popular debates around food in schools are largely connected with biomedical issues of obesity, exercise and nutrition. This is a study of the sociological dimensions of food-related messages, practices and knowledge formations in the primary school curriculum. It uses an exploratory, qualitative case study methodology to identify and examine the food activities of a Year 5 class in a Queensland school. Data was gathered over a twoyear period using observation, documentation and interviews methods. Food was found to be an integral part of the primary school's activity. It had economic, symbolic, pedagogic, and instrumental value. Messages about food were found in the official, enacted and hidden curricular which were framed by a food governance framework of legislation, procedures and norms. In the school studied, food knowledge was commodified as a part of a political economy that centred on an 'eat more' message. Certain foods were privileged over others while myths about energy, fruit, fruit juice and sugar shaped student dispositions, values, norms and action. There was little engagement with the cognitive and behavioural dimensions of food and nutrition. The thesis concludes with recommendations for a whole scale reconsideration of food in schools as curricular content and knowledge.

Investigating the impact of a leadership development program for nurse unit managers on the satisfaction of nursing staff

Background and significance: Nurses' job dissatisfaction is associated with negative nursing and patient outcomes. One of the most powerful reasons for nurses to stay in an organisation is satisfaction with leadership. However, nurses are frequently promoted to leadership positions without appropriate preparation for the role. Although a number of leadership programs have been described, none have been tested for effectiveness, using a randomised control trial methodology. Aims: The aims of this research were to develop an evidence based leadership program and to test its effectiveness on nurse unit managers' (NUMs') and nursing staff's (NS's) job satisfaction, and on the leader behaviour scores of nurse unit managers. Methods: First, the study used a comprehensive literature review to examine the evidence on job satisfaction, leadership and front-line manager competencies. From this evidence a summary of leadership practices was developed to construct a two component leadership model. The components of this model were then combined with the evidence distilled from previous leadership development programs to develop a Leadership Development Program (LDP). This evidence integrated the program's design, its contents, teaching strategies and learning environment. Central to the LDP were the evidence-based leadership practices associated with increasing nurses' job satisfaction. A randomised controlled trial (RCT) design was employed for this research to test the effectiveness of the LDP. A RCT is one of the most powerful tools of research and the use of this method makes this study unique, as a RCT has never been used previously to evaluate any leadership program for front-line nurse managers. Thirty-nine consenting nurse unit managers from a large tertiary hospital were randomly allocated to receive either the leadership program or only the program's written information about leadership. Demographic baseline data were collected from participants in the NUM groups and the nursing staff who reported to them. Validated questionnaires measuring job satisfaction and leader behaviours were administered at baseline, at three months after the commencement of the intervention and at six months after the commencement of the intervention, to the nurse unit managers and to the NS. Independent and paired t-tests were used to analyse continuous outcome variables and Chi Square tests were used for categorical data. Results: The study found that the nurse unit managers' overall job satisfaction score was higher at 3-months (p = 0.016) and at 6-months p = 0.027) post commencement of the intervention in the intervention group compared with the control group. Similarly, at 3-months testing, mean scores in the intervention group were higher in five of the six "positive" sub-categories of the leader behaviour scale when compared to the control group. There was a significant difference in one sub-category; effectiveness, p = 0.015. No differences were observed in leadership behaviour scores between groups by 6-months post commencement of the intervention. Over time, at three month and six month testing there were significant increases in four transformational leader behaviour scores and in one positive transactional leader behaviour scores in the intervention group. Over time at 3-month testing, there were significant increases in the three leader behaviour outcome scores, however at 6-months testing; only one of these leader behaviour outcome scores remained significantly increased. Job satisfaction scores were not significantly increased between the NS groups at three months and at six months post commencement of the intervention. However, over time within the intervention group at 6-month testing there was a significant increase in job satisfaction scores of NS. There were no significant increases in NUM leader behaviour scores in the intervention group, as rated by the nursing staff who reported to them. Over time, at 3-month testing, NS rated nurse unit managers' leader behaviour scores significantly lower in two leader behaviours and two leader behaviour outcome scores. At 6-month testing, over time, one leader behaviour score was rated significantly lower and the nontransactional leader behaviour was rated significantly higher. Discussion: The study represents the first attempt to test the effectiveness of a leadership development program (LDP) for nurse unit managers using a RCT. The program's design, contents, teaching strategies and learning environment were based on a summary of the literature. The overall improvement in role satisfaction was sustained for at least 6-months post intervention. The study's results may reflect the program's evidence-based approach to developing the LDP, which increased the nurse unit managers' confidence in their role and thereby their job satisfaction. Two other factors possibly contributed to nurse unit managers' increased job satisfaction scores. These are: the program's teaching strategies, which included the involvement of the executive nursing team of the hospital, and the fact that the LDP provided recognition of the importance of the NUM role within the hospital. Consequently, participating in the program may have led to nurse unit managers feeling valued and rewarded for their service; hence more satisfied. Leadership behaviours remaining unchanged between groups at the 6 months data collection time may relate to the LDP needing to be conducted for a longer time period. This is suggested because within the intervention group, over time, at 3 and 6 months there were significant increases in self-reported leader behaviours. The lack of significant changes in leader behaviour scores between groups may equally signify that leader behaviours require different interventions to achieve change. Nursing staff results suggest that the LDP's design needs to consider involving NS in the program's aims and progress from the outset. It is also possible that by including regular feedback from NS to the nurse unit managers during the LDP that NS's job satisfaction and their perception of nurse unit managers' leader behaviours may alter. Conclusion/Implications: This study highlights the value of providing an evidence-based leadership program to nurse unit managers to increase their job satisfaction. The evidence based leadership program increased job satisfaction but its effect on leadership behaviour was only seen over time. Further research is required to test interventions which attempt to change leader behaviours. Also further research on NS' job satisfaction is required to test the indirect effects of LDP on NS whose nurse unit managers participate in LDPs.

An Australian study on partnerships to promote school to work transitions

The delivery of vocational education and training (VET) is being challenged by either increasing skills shortages and/or rapidly changing skill requirements. To respond to this challenge, centralised state bureaucracies are increasingly adopting partnerships between schools and industry as a strategy to encourage school to work transition programs to address the local labour market demand. This paper reports on an Australian case study of government-led partnerships named the Queensland Gateway to industry schools initiative. 12 out of 120 school industry partnerships from five industry sectors were analysed in terms of the two commonly identified principles derived from the public-private partnership literature; efficiency and effectiveness. The study found that efficiency and effectiveness benefits of partnership activities were attributed to Gateway schools projects by both school and industry stakeholders. However, little evidence was found that the above underlying principles were addressed systematically. Implications are that project stakeholders would benefit from adapting theoretical perspectives regarding the implementation and management of partnerships to ensure the sustainability of partnerships.

Vocational education in science, technology, engineering and maths (STEM) : Curriculum innovation through school industry partnerships

Governments have recognised that the technological trades rely on knowledge embedded traditionally in science, technology, engineering and mathematics (STEM) disciplines. However, there is substantial evidence that students are turning away from these subjects in schools because the school curriculum is seen as irrelevant, with clear implications for not just vocational education but also higher education. In this paper, we report preliminary findings on the development of two curricula that attempt to integrate science and mathematics with workplace knowledge and practices. We argue that these curricula provide educational opportunities for students to pursue their preferred career pathways. These curricula were co-developed by industry and educational personnel across three industry sectors, namely, mining industry, aerospace and wine tourism. The aim was to provide knowledge appropriate for students moving from school to the workplace as trade apprentices in the respective industries. The analysis of curriculum and associated policy documents reveals that the curricula adopt applied learning orientations through teaching strategies and assessment practices which focus on practical skills. However, although key theoretical science and maths concepts have been well incorporated, the extent to which knowledge deriving from workplace practices is included varies across the curricula. The extent to which applications of concepts are included in the models depends on a number of factors not least the relevant expertise of the teacher as a practitioner in the industry. Our findings highlight the importance of teachers having substantial practical industry experience and the role that whole school policies play in attempts to align the range of learning experiences with the needs of industry.

School industry partnerships : An innovative strategy for vocational education

One of the challenges confronting contemporary education internationally is to ensure that students are provided with opportunities to make informed choices about future careers and to acquire the capacity to transition into these careers. Schools need to manage their curricula, teacher capacity, timetables, and diversity of student populations by offering pathways that are seen as engaging and meaningful to life beyond schooling. Traditionally, education in the senior years has privileged those students who intend to progress to advanced studies at university or in other professional careers. In more recent times, in response the need for more sophisticated technical knowledge in the trades and a growing skills shortages in these fields, schools have paid more attention to vocational education. It has been argued that the vocational aspect of the school curriculum is less well understood and poorly implemented in comparison with the traditional academic curricula. One attempt to address this issue is through the establishment of school-industry partnerships. This paper explores the process of knowledge transfer between industry and schools in these partnerships. The paper theorises how knowledge that is valued and foundational in workplace employment can inform school curricula and pedagogical practices. The paper draws on theories of organisational knowledge, workplace learning and experiential learning to explore strategies that enhance school-to-employment transition outcomes.

Industry school partnerships: Boundary crossing to enable school to work transitions

Industry-school partnerships (ISPs) are increasingly being recognised as a new way of providing vocational education opportunities. However, there is limited research investigating their impact on school to work transitions. This paper reports on a government-led ISP, the Gateway to Industry Schools Program, established in Queensland, Australia. Central to this initiative is the Queensland Minerals and Energy Academy (QMEA), a lead organisation for 28 schools and 17 multi-national sponsor companies. This research adopted a qualitative case study methodology and draws upon boundary crossing theory as means to understand a Minerals and Energy ISP. We distinguish four types of boundary crossing mechanisms, which align with principles for effectiveness in ISPs. The main findings were that boundary crossing mechanisms assist ISPs to develop industry-based contextualised curriculum and to prepare school students for employment.

An exploratory study to evaluate whether medical nutrition therapy can improve dietary intake in hospital patients who eat poorly

Background and aims The Australasian Nutrition Care Day Survey (ANCDS) reported two-in-five patients consume ≤50% of the offered food in Australian and New Zealand hospitals. After controlling for confounders (nutritional status, age, disease type and severity), the ANCDS also established an independent association between poor food intake and increased in-hospital mortality. This study aimed to evaluate if medical nutrition therapy (MNT) could improve dietary intake in hospital patients eating poorly. Methods An exploratory pilot study was conducted in the respiratory, neurology and orthopaedic wards of an Australian hospital. At baseline, percentage food intake (0%, 25%, 50%, 75%, and 100%) was evaluated for each main meal and snack for a 24-hour period in patients hospitalised for ≥2 days and not under dietetic review. Patients consuming ≤50% of offered meals due to nutrition-impact symptoms were referred to ward dietitians for MNT. Food intake was re-evaluated on the seventh day following recruitment (post-MNT). Results 184 patients were observed over four weeks; 32 patients were referred for MNT. Although baseline and post-MNT data for 20 participants (68±17years, 65% females) indicated a significant increase in median energy and protein intake post-MNT (3600kJ/day, 40g/day) versus baseline (2250kJ/day, 25g/day) (p<0.05), the increased intake met only 50% of dietary requirements. Persistent nutrition impact symptoms affected intake. Conclusion In this pilot study whilst dietary intake improved, it remained inadequate to meet participants’ estimated requirements due to ongoing nutrition-impact symptoms. Appropriate medical management and early enteral feeding could be a possible solution for such patients.

The experience of being an advanced practice nurse within Australian acute care settings : a systematic review of qualitative evidence

Background There is a vast amount of international literature which, although agreeing on the need for advanced practice nurse roles, simultaneously debates and discusses the difficulties with nomenclature, definition and subsequent implementation of such roles. Due to this ambiguity it is difficult to equally compare evidence in this field across different countries. A context-specific systematic review on the qualitative evidence of the experience of being an advanced practice nurse in Australia has not been undertaken previously, however it is imperative for nursing managers and leaders to understand the complexities of advanced nursing roles in order to effectively utilise and retain these experienced and valuable nurses. With the creation of a national nursing regulating authority in 2010, it is timely to explore in-depth the experience of being an advanced practice nurse from a national perspective. Objective To identify the experience of being an advanced practice nurse working in Australian acute care settings. Inclusion criteria -Types of participants Registered nurses working in advanced practice roles in acute care settings throughout Australia. -Phenomena of interest The experience of being an advanced practice registered nurse working in an Australian acute care setting, as reported by the nurses themselves. -Types of studies Interpretive qualitative studies including designs such as phenomenology, grounded theory and ethnography. -Search strategy A three step search strategy was used to identify published and unpublished studies. The search process was conducted from August to October 2011 and considered published and unpublished studies from 1990 to October 2011. -Methodological quality Studies were appraised for methodological quality by two independent reviewers using the Joanna Briggs Qualitative Assessment and Review Instrument. -Data extraction Data was extracted from the papers included in the review using the standardised Joanna Briggs Institute Qualitative Assessment and Review Instrument data extraction tool. -Data synthesis Research findings were pooled using the Joanna Briggs Institute Qualitative Data and Review Instrument. Results Three published studies and one unpublished dissertation were included in the review. From these four studies, 216 findings were extracted, forming 18 categories which were then analysed to create six synthesised findings. Six meta-syntheses under the headings of expert knowledge, confidence, education, relationships, negative experiences and patient centred experience were formed from the findings. Conclusions The synthesised findings confirm that the experience of advanced practice nurses in Australian acute care settings is complex and greatly influenced personally and professionally by the organisation as well as the unpredictable nature of working with people.

Choroidal thickness in childhood

Purpose To examine choroidal thickness (ChT) and its spatial distribution across the posterior pole in pediatric subjects with normal ocular health and minimal refractive error. Methods ChT was assessed using spectral domain optical coherence tomography (OCT) in 194 children aged between 4-12 years, with spherical equivalent refractive errors between +1.25 and -0.50 DS. A series of OCT scans were collected, imaging the choroid along 4 radial scan lines centered on the fovea (each separated by 45°). Frame averaging was used to reduce noise and enhance chorio-scleral junction visibility. The transverse scale of each scan was corrected to account for magnification effects associated with axial length. Two independent masked observers manually segmented the OCT images to determine ChT at foveal centre, and averaged across a series of perifoveal zones over the central 5 mm. Results The average subfoveal ChT was 330 ± 65 µm (range 189-538 µm), and was significantly influenced by age (p=0.04). The ChT of the 4 to 6 year old age group (312 ± 62 µm) was significantly thinner compared to the 7 to 9 year olds (337 ± 65 µm, p<0.05) and bordered on significance compared to the 10 to 12 year olds (341 ± 61 µm, p=0.08). ChT also exhibited significant variation across the posterior pole, being thicker in more central regions. The choroid was thinner nasally and inferiorly compared to temporally and superiorly. Multiple regression analysis revealed age, axial length and anterior chamber depth were significantly associated with subfoveal ChT (p<0.001). Conclusions ChT increases significantly from early childhood to adolescence. This appears to be a normal feature of childhood eye growth.

Packed red blood cells suppress myeloid dendritic cell and monocyte inflammatory responses in a whole blood model of transfusion

Purpose/Objective: The basis for poor outcomes in some patients post transfusion remains largely unknown. Despite leukodepletion, there is still evidence of immunomodulatory effects of transfusion that require further study. In addition, there is evidence that the age of blood components transfused significantly affects patient outcomes. Myeloid dendritic cell (DC) and monocyte immune function were studied utilising an in vitro whole blood model of transfusion. Materials and methods: Freshly collected (‘recipient’) whole blood was cultured with ABO compatible leukodepleted PRBC at 25% blood replacement-volume (6hrs). PRBC were assayed at [Day (D) 2, 14, 28and 42 (date-of expiry)]. In parallel, LPS or Zymosan (Zy) were added to mimic infection. Recipients were maintained for the duration of the time course (2 recipients, 4 PRBC units, n = 8).Recipient DC and monocyte intracellular cytokines and chemokines (IL-6, IL-10, IL-12,TNF-a, IL-1a, IL-8, IP-10, MIP-1a, MIP-1b, MCP-1) were measured using flow cytometry. Changes in immune response were calculated by comparison to a parallel no transfusion control (Wilcoxin matched pairs). Influence of storage age was calculated using ANOVA. Results: Significant suppression of DC and monocyte inflammatory responses were evident. DC and monocyte production of IL-1a was reduced following exposure to PRBC regardless of storage age (P < 0.05 at all time points). Storage independent PRBC mediated suppression of DC and monocyte IL-1a was also evident in cultures costimulated with Zy. In cultures co-stimulated with either LPS or Zy, significant suppression of DC and monocyte TNF-a and IL-6 was also evident. PRBC storage attenuated monocyte TNF-a production when co-cultured with LPS (P < 0.01 ANOVA). DC and monocyte production of MIP-1a was significantly reduced following exposure to PRBC (DC: P < 0.05 at D2, 28, 42; Monocyte P < 0.05 all time points). In cultures co-stimulated with LPS and zymosan, a similar suppression of MIP-1a production was also evident, and production of both DC and monocyte MIP-1b and IP-10 were also significantly reduced. Conclusions: The complexity of the transfusion context was reflected in the whole blood approach utilised. Significant suppression of these key DC and monocyte immune responses may contribute to patient outcomes, such as increased risk of infection and longer hospital stay, following blood transfusion.

Construal level and ingroup bias

The causal relationship between mental construal level and ingroup bias remains elusive. This paper uncovers a boundary condition and a mechanism underlying the relationship. We predict and find support for our hypotheses in four experiments conducted in East Asian and Western cultures. Data showed that a high- (vs. low-) level construal activated state belongingness, but had no effect on state rejection, state self-esteem, positive emotion, or negative emotion in participants from Korea (Experiment 1) and Australia (Experiment 3). Moreover, a high- (vs. low-) level construal triggered greater ingroup bias for Koreans (Experiment 2) and Australians (Experiment 3) primed with a relational self, but not for those primed with an independent self. This construal level effect on ingroup bias was eliminated when belongingness was primed at both a high- and a low-level construal; instead, relationals under a low-level construal were more ingroup-biased when they were primed with a belongingness (vs. baseline) condition (Experiment 4). These findings highlight that the relational self is a boundary condition for the construal level-ingroup bias link; belongingness explains the relationship.

Depression scores predict adherence in a dietary weight loss intervention trial

Background & aims Depression has a complex association with cardiometabolic risk, both directly as an independent factor and indirectly through mediating effects on other risk factors such as BMI, diet, physical activity, and smoking. Since changes to many cardiometabolic risk factors involve behaviour change, the rise in depression prevalence as a major global health issue may present further challenges to long-term behaviour change to reduce such risk. This study investigated associations between depression scores and participation in a community-based weight management intervention trial. Methods A group of 64 overweight (BMI > 27), otherwise healthy adults, were recruited and randomised to follow either their usual diet, or an isocaloric diet in which saturated fat was replaced with monounsaturated fat (MUFA), to a target of 50% total fat, by adding macadamia nuts to the diet. Subjects were assessed for depressive symptoms at baseline and at ten weeks using the Beck Depression Inventory (BDI-II). Both control and intervention groups received advice on National Guidelines for Physical Activity and adhered to the same protocol for food diary completion and trial consultations. Anthropometric and clinical measurements (cholesterol, inflammatory mediators) also were taken at baseline and 10 weeks. Results During the recruitment phase, pre-existing diagnosed major depression was one of a range of reasons for initial exclusion of volunteers from the trial. Amongst enrolled participants, there was a significant correlation (R = −0.38, p < 0.05) between BDI-II scores at baseline and duration of participation in the trial. Subjects with a baseline BDI ≥10 (moderate to severe depression symptoms) were more likely to dropout of the trial before week 10 (p < 0.001). BDI-II scores in the intervention (MUFA) diet group decreased, but increased in the control group over the 10-week period. Univariate analysis of variance confirmed these observations (adjusted R2 = 0.257, p = 0.01). Body weight remained static over the 10-week period in the intervention group, corresponding to a relative increase in the control group (adjusted R2 = 0.097, p = 0.064). Conclusions Depression symptoms have the potential to affect enrolment in and adherence to dietbased risk reduction interventions, and may consequently influence the generalisability of such trials. Depression scores may therefore be useful for characterising, screening and allocating subjects to appropriate treatment pathways.