Partners in Play: How Children Organise their Participation in Sociodramatic Play

In Ireland, early childhood learning and the role of play in children’s lives is receiving unprecedented recognition in national policy documents (Ireland, 1999c, 1999a, 1999b, 2000, 2004, N.C.C.A., 2004, C.E.C.D.E., 2006b). This thesis links learning and play and proposes to contribute to our understanding of both. The purpose of the research is to explicate the significant processes and outcomes of children’s participation in sociodramatic play. It takes a qualitative, ethnographic, interpretive approach which follows logically from the aim and the sociocultural discourse of learning constructed. This sociocultural discourse frames the observation and analysis of sociodramatic play in the study. Three key elements of sociocultural theory become the themes that are explored. They are (1) that children’s participation in play is mediated by culture, (2) that the processes and outcomes of sociodramatic play are negotiated on the intermental plane at the micro level of face to face interaction and at the macro level of transaction with cultural goals, values, artefacts and practices and (3) that in the process of participation in sociodramatic play, both culture and participants are transformed towards ongoing participation. The study is conducted primarily through participant observation in a suburban preschool playgroup with a cohort of 22 children ranging in age from 2 years and 8 months to 4 years and 9 months, over an academic year. The data consists of play episodes and field notes documented with the support of video recordings and analysed using Rogoff’s (1995) three planes of analysis. These planes align with the three themes of the research and provide the structure for the analysis chapters. The Community or Apprenticeship Plane is used to demonstrate the cultural nature of sociodramatic play. The Interpersonal or Guided Participation Plane serves to identify the interactive processes and outcomes in which children participate, while on the Individual or Participatory Appropriation Plane, outcomes in terms of cultural and personal transformations are considered. The findings of this research emerge from both the explication of sociocultural theory and the dialectic between the theoretical perspective and the play episodes. The theoretical perspective itself is a key contribution, with implications for early childhood education and the place of sociodramatic play. The study further explicates the processes of learning on the intermental plane and thereby informs the role of the early childhood pedagogue. Key play competencies, particularly emotional intersubjectivity, are identified. The ethnographic approach allows us to follow children’s transformations as they reconstruct, through their sociodramatic play roles and stories, their ways of belonging, contributing and communicating within the peer culture. The findings propose an individual-in-social activity centred pedagogy – a pedagogy of connection - with philosophical and practical implications for the practice of pedagogy

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Counting on commitment; the quality of primary care-led diabetes management in a system with minimal incentives

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to assess the performance of three primary care-led initiatives providing structured care to patients with Type 2 diabetes in Ireland, a country with minimal incentives to promote the quality of care.</p> <p>Methods</p> <p>Data, from three primary care initiatives, were available for 3010 adult patients with Type 2 diabetes. Results were benchmarked against the national guidelines for the management of Type 2 diabetes in the community and results from the National Diabetes Audit (NDA) for England (2008/2009) and the Scottish Diabetes Survey (2009).</p> <p>Results</p> <p>The recording of clinical processes of care was similar to results in the UK however the recording of lifestyle factors was markedly lower. Recording of HbA1c, blood pressure and lipids exceeded 85%. Recording of retinopathy screening (71%) was also comparable to England (77%) and Scotland (90%). Only 63% of patients had smoking status recorded compared to 99% in Scotland while 70% had BMI recorded compared to 89% in England. A similar proportion of patients in this initiative and the UK achieved clinical targets. Thirty-five percent of patients achieved a target HbA1c of < 6.5% (< 48 mmol/mol) compared to 25% in England. Applying the NICE target for blood pressure (≤ 140/80 mmHg), 54% of patients reached this target comparable to 60% in England. Slightly less patients were categorised as obese (> 30 kg/m²) in Ireland (50%, n = 1060) compared to Scotland (54%).</p> <p>Conclusions</p> <p>This study has demonstrated what can be achieved by proactive and interested health professionals in the absence of national infrastructure to support high quality diabetes care. The quality of primary care-led diabetes management in the three initiatives studied appears broadly consistent with results from the UK with the exception of recording lifestyle factors. The challenge facing health systems is to establish quality assurance a responsibility for all health care professionals rather than the subject of special interest for a few.</p

Multinational firms' motivations and foreign direct investment decisions : an analysis of the software & IT and financial services sectors in the Irish context

The paper focuses on the way greenfield foreign direct investment in different sectors is influenced by locational characteristics and explores the role of policy in attracting and retaining foreign investment. We contribute to the literature by empirically investigating the investment motivations of multinational companies in the Software & IT and Financial Services sectors in Ireland and those locational factors that contribute to the retention of foreign direct investment. The methodology used in this research is of a qualitative nature and an exploratory deductive approach is adopted in order to gain an understanding of firms’ internationalisation decisions and motivations. The data demonstrates that companies in the two sectors follow different investment motivations. Firms in the Software & IT sector entered Ireland primarily because of the availability of a high quality workforce. Whereas firms in the Financial Services sector entered Ireland following the deregulation of markets and the subsequent ease of doing business. The paper builds on these findings to develop policy recommendations

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping on the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C8197/A16565), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combination of the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative, grant 1 U19 CA148065-01 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.324

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk : a case-control study

Abstract Introduction We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. Methods We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P trend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P trend = 0.005) but not cases (P trend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P het = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; P trend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; P trend = 0.29). Conclusions To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels