Genome-wide linkage and association analyses implicate FASN in predisposition to Uterine Leiomyomata

Uterine leiomyomata (UL), the most prevalent pelvic tumors in women of reproductive age, pose a major public health problem given their high frequency, associated morbidities, and most common indication for hysterectomies. A genetic component to UL predisposition is supported by analyses of ethnic predisposition, twin studies, and familial aggregation. A genome-wide SNP linkage panel was genotyped and analyzed in 261 white UL-affected sister-pair families from the Finding Genes for Fibroids study. Two significant linkage regions were detected in 10p11 (LOD = 4.15) and 3p21 (LOD = 3.73), and five additional linkage regions were identified with LOD scores > 2.00 in 2q37, 5p13, 11p15, 12q14, and 17q25. Genome-wide association studies were performed in two independent cohorts of white women, and a meta-analysis was conducted. One SNP (rs4247357) was identified with a p value (p = 3.05 x 10(-8)) that reached genome-wide significance (odds ratio = 1.299). The candidate SNP is under a linkage peak and in a block of linkage disequilibrium in 17q25.3, which spans fatty acid synthase (FASN), coiled-coil-domain-containing 57 (CCDC57), and solute-carrier family 16, member 3 (SLC16A3). By tissue microarray immunohistochemistry, we found elevated (3-fold) FAS levels in UL-affected tissue compared to matched myometrial tissue. FAS transcripts and/or protein levels are upregulated in various neoplasms and implicated in tumor cell survival. FASN represents the initial UL risk allele identified in white women by a genome-wide, unbiased approach and opens a path to management and potential therapeutic intervention.

Further evidence for linkage of Gilles de la Tourette syndrome (GTS) susceptibility loci on chromosomes 2p11, 8q22 and 11q23-24 in South African Afrikaners

Utilizing DNA samples from 91 Afrikaner nuclear families with one or more affected children, five genomic regions on chromosomes 2p, 8q, 11q, 20q, and 21q that gave evidence for association with GTS in previous case-control association studies were investigated for linkage and association with GTS. Highly polymorphic markers with mean heterozygosity of 0.77 were typed and resulting genotypes evaluated using single marker transmission disequilibrium (TDT), single marker haplotype relative risk (HRR), and multi-marker "extended" TDT and HRR methods. Single marker TDT analysis showed evidence for linkage or association, with p-values near 0.05, for markers D2S139, GATA28F12, and D11S1377 on chromosomes 2p11, 8q22 and 11q23-24, respectively. Extended, two-locus TDT and HRR analysis provided further evidence for linkage or association on chromosome 2 with p-values of 0.007 and 0.025, and chromosome 8 with p-values of 0.059 and 0.013, respectively. These results provide important additional evidence for the location of GTS susceptibility loci.

Systematic review of the psychological consequences of false-positive screening mammograms

- Background In the UK, women aged 50–73 years are invited for screening by mammography every 3 years. In 2009–10, more than 2.24 million women in this age group in England were invited to take part in the programme, of whom 73% attended a screening clinic. Of these, 64,104 women were recalled for assessment. Of those recalled, 81% did not have breast cancer; these women are described as having a false-positive mammogram. - Objective The aim of this systematic review was to identify the psychological impact on women of false-positive screening mammograms and any evidence for the effectiveness of interventions designed to reduce this impact. We were also looking for evidence of effects in subgroups of women. - Data sources MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Health Management Information Consortium, Cochrane Central Register for Controlled Trials, Cochrane Database of Systematic Reviews, Centre for Reviews and Dissemination (CRD) Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment (HTA), Cochrane Methodology, Web of Science, Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index-Science, Conference Proceeding Citation Index-Social Science and Humanities, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Sociological Abstracts, the International Bibliography of the Social Sciences, the British Library's Electronic Table of Contents and others. Initial searches were carried out between 8 October 2010 and 25 January 2011. Update searches were carried out on 26 October 2011 and 23 March 2012. - Review methods Based on the inclusion criteria, titles and abstracts were screened independently by two reviewers. Retrieved papers were reviewed and selected using the same independent process. Data were extracted by one reviewer and checked by another. Each included study was assessed for risk of bias. - Results Eleven studies were found from 4423 titles and abstracts. Studies that used disease-specific measures found a negative psychological impact lasting up to 3 years. Distress increased with the level of invasiveness of the assessment procedure. Studies using instruments designed to detect clinical levels of morbidity did not find this effect. Women with false-positive mammograms were less likely to return for the next round of screening [relative risk (RR) 0.97; 95% confidence interval (CI) 0.96 to 0.98] than those with normal mammograms, were more likely to have interval cancer [odds ratio (OR) 3.19 (95% CI 2.34 to 4.35)] and were more likely to have cancer detected at the next screening round [OR 2.15 (95% CI 1.55 to 2.98)]. - Limitations This study was limited to UK research and by the robustness of the included studies, which frequently failed to report quality indicators, for example failure to consider the risk of bias or confounding, or failure to report participants' demographic characteristics. - Conclusions We conclude that the experience of having a false-positive screening mammogram can cause breast cancer-specific psychological distress that may endure for up to 3 years, and reduce the likelihood that women will return for their next round of mammography screening. These results should be treated cautiously owing to inherent weakness of observational designs and weaknesses in reporting. Future research should include a qualitative interview study and observational studies that compare generic and disease-specific measures, collect demographic data and include women from different social and ethnic groups.

Editorial of "International Journal of Critical Indigenous Studies, Volume 7, Number 1, 2014"

This edition testifies to the broad international reach of the journal, with contributions variously concerned with Arctic Indigenous communities, the Métis of Canada, Native Hawaiians and Māori of Aotearoa (New Zealand). Two articles stress the need to work collaboratively and respectfully with Indigenous populations whilst conducting research. The first, by Gwen Healey, notes the increased interest in health research in the Arctic, particularly with Inuit populations. Healy seeks to add to the growing body of literature concerned with Indigenous ways of knowing by highlighting Inuit concepts that inform an effective Arctic research model. The second, by primary author Peter Hutchinson and a range of co-contributors, highlights the ways in which Métis collaborators working in health developed a participatory Indigenous research method that was unique in that it foregrounded Métis relationships and relationality. In so doing, the researchers were able to give substance to otherwise staid policy statements about the need for good ethical research conduct.

Bringing nature to schools to promote children’s physical activity

Physical activity (PA) is essential for human health and wellbeing across all age, socioeconomic and ethnic groups. Engagement with the natural world is a new defining criterion for enhancing the benefits of PA particularly for children and young people. Interacting with nature benefits children’s social and emotional wellbeing, develops resilience and reduces the risk of obesity and type 2 diabetes across all population groups. Governments around the world are now recognising the importance of children spending more active time outdoors. However, children’s outdoor activities, free play and nature-related exploration are often structured and supervised by adults due to safety concerns and risks. In this context schools become more accessible and safe options for children to engage in PA outdoors with the presence of nature features. Research on school designs involving young children has revealed that children prefer nature-related features in school environments. Affordances in nature may increase children’s interest in physically active behaviours. Given that present school campuses are designed for operational efficiency and economic reasons there is a need to re-design schools responding to the positive role of nature on human health. If schools were re-designed to incorporate diverse natural features children’s PA and consequent health and wellbeing would likely improve markedly.

Reconstituting identity and history in post-war Mostar, Bosnia-Herzegovina

This paper by Carl Grodach demonstrates the careful unravelling of complexity, diversity, contestation and contradictions involved in the reconstruction of symbolic urban spaces after violent conflict, and the allied processes of cultural reinterpretation, political reconfiguration and material revaluation which accompany it. The paper analyses the reconstruction and redevelopment of the 16th-century historic centre of Mostar, Bosnia-Herzegovina, following the Bosnian Wars of 1992–1995. Reconstruction efforts centre around Stari Most, the 16th-century Ottoman bridge destroyed by Bosnian Croat military in 1993. In Mostar, both international and local organizations are in the process of reinterpreting Bosnia’s legacy of Ottoman city spaces. This research and analysis illuminates how such spaces can be central to contemporary projects to redefine group identities and conceptions of place. It provides insight into the ways various groups are attempting to reshape outside perceptions of the city—and Bosnia’s ethnic conflict—to articulate a new definition of local identity and ethnic relations and to remake a stable tourist economy through Mostar’s urban spaces.

Clancestry Conversation Series

The Clancestry Conversation series forms part of QPAC's Clancestry Festival which is an annual celebration of the arts and cultural practices of the world's First Nations Peoples with a particular focus on Aboriginal and Torres Strait Islander peoples.

Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials

Background We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label, randomised, phase 3 trials. Methods Previously untreated patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma were enrolled in LUX-Lung 3 (n=345) and LUX-Lung 6 (n=364). These patients were randomly assigned in a 2:1 ratio to receive afatinib or chemotherapy (pemetrexed-cisplatin [LUX-Lung 3] or gemcitabine-cisplatin [LUX-Lung 6]), stratified by EGFR mutation (exon 19 deletion [del19], Leu858Arg, or other) and ethnic origin (LUX-Lung 3 only). We planned analyses of mature overall survival data in the intention-to-treat population after 209 (LUX-Lung 3) and 237 (LUX-Lung 6) deaths. These ongoing studies are registered with ClinicalTrials.gov, numbers NCT00949650 and NCT01121393. Findings Median follow-up in LUX-Lung 3 was 41 months (IQR 35–44); 213 (62%) of 345 patients had died. Median follow-up in LUX-Lung 6 was 33 months (IQR 31–37); 246 (68%) of 364 patients had died. In LUX-Lung 3, median overall survival was 28·2 months (95% CI 24·6–33·6) in the afatinib group and 28·2 months (20·7–33·2) in the pemetrexed-cisplatin group (HR 0·88, 95% CI 0·66–1·17, p=0·39). In LUX-Lung 6, median overall survival was 23·1 months (95% CI 20·4–27·3) in the afatinib group and 23·5 months (18·0–25·6) in the gemcitabine-cisplatin group (HR 0·93, 95% CI 0·72–1·22, p=0·61). However, in preplanned analyses, overall survival was significantly longer for patients with del19-positive tumours in the afatinib group than in the chemotherapy group in both trials: in LUX-Lung 3, median overall survival was 33·3 months (95% CI 26·8–41·5) in the afatinib group versus 21·1 months (16·3–30·7) in the chemotherapy group (HR 0·54, 95% CI 0·36–0·79, p=0·0015); in LUX-Lung 6, it was 31·4 months (95% CI 24·2–35·3) versus 18·4 months (14·6–25·6), respectively (HR 0·64, 95% CI 0·44–0·94, p=0·023). By contrast, there were no significant differences by treatment group for patients with EGFR Leu858Arg-positive tumours in either trial: in LUX-Lung 3, median overall survival was 27·6 months (19·8–41·7) in the afatinib group versus 40·3 months (24·3–not estimable) in the chemotherapy group (HR 1·30, 95% CI 0·80–2·11, p=0·29); in LUX-Lung 6, it was 19·6 months (95% CI 17·0–22·1) versus 24·3 months (19·0–27·0), respectively (HR 1·22, 95% CI 0·81–1·83, p=0·34). In both trials, the most common afatinib-related grade 3–4 adverse events were rash or acne (37 [16%] of 229 patients in LUX-Lung 3 and 35 [15%] of 239 patients in LUX-Lung 6), diarrhoea (33 [14%] and 13 [5%]), paronychia (26 [11%] in LUX-Lung 3 only), and stomatitis or mucositis (13 [5%] in LUX-Lung 6 only). In LUX-Lung 3, neutropenia (20 [18%] of 111 patients), fatigue (14 [13%]) and leucopenia (nine [8%]) were the most common chemotherapy-related grade 3–4 adverse events, while in LUX-Lung 6, the most common chemotherapy-related grade 3–4 adverse events were neutropenia (30 [27%] of 113 patients), vomiting (22 [19%]), and leucopenia (17 [15%]). Interpretation Although afatinib did not improve overall survival in the whole population of either trial, overall survival was improved with the drug for patients with del19 EGFR mutations. The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials.

ACE Research Vignette 050: What makes new migrant businesses grow? Connections or location?

This series of research vignettes is aimed at sharing current and interesting research findings from our team of international Entrepreneurship researchers. In this vignette, Dr. Roxanne Zolin and Dr. Artemis Chang consider both the role of ethnic connections and location in an ethnic neighbourhood on new migrant business growth.

Social networks and use of social supports of minority elders in East Harlem

Considerable empirical research substantiates the importance of social networks on health and well-being in later life. A study of ethnic minority elders living in two low income public housing buildings in East Harlem was undertaken to gain an understanding of the relationship between their health status and social networks. Findings demonstrate that elders with supportive housing had better psychological outcomes and used significantly more informal supports when in need. However, elders with serious health problems had poorer outcomes regardless of their level of social support. This study highlights the potential of supportive living environments to foster social integration and to optimise formal and informal networks.

A cultural assessment of family dispute resolution: Findings about access, retention and outcomes from the evaluation of a Family Relationship Centre

The cultural appropriateness of human service processes is a major factor in determining the effectiveness of their delivery. Sensitivity to issues of culture is particularly critical in dealing with family disputes, which are generally highly emotive and require difficult decisions to be made regarding children, material assets and ongoing relationships. In this article we draw on findings from an evaluation of the Family Relationship Centre at Broadmeadows (FRCB) to offer some insights into and suggestions about managing cultural matters in the current practice of family dispute resolution (FDR) in Australia. The brief for the original research was to evaluate the cultural appropriateness of FDR services offered to culturally and linguistically diverse (CALD) communities living within the FRCB’s catchment area, specifically members of the Lebanese, Turkish and Iraqi communities. The conclusions of the evaluations were substantially positive. The work of the Centre was found to illustrate many aspects of best practice but also raised questions worthy of future exploration. The current article reports on issues of access, retention and outcomes obtained by CALD clients at various stages of the FRCB service.

A cultural assessment of family dispute resolution: Findings about cultural appropriateness from the evaluation of a family relationship centre

The cultural appropriateness of human service processes is a major factor in determining the effectiveness of their delivery. Sensitivity to issues of culture is particularly critical in dealing with family disputes, which are generally highly emotive and require difficult decisions to be made regarding children, material assets and ongoing relationships. In this article we draw on findings from an evaluation of the Family Relationship Centre at Broadmeadows (FRCB) to offer some insights into and suggestions about managing cultural matters in the current practice of family dispute resolution (FDR) in Australia. The brief for the original research was to evaluate the cultural appropriateness of FDR services offered to culturally and linguistically diverse (CALD) communities living within the FRCB’s catchment area, specifically members of the Lebanese, Turkish and Iraqi communities. The conclusions of the evaluations were substantially positive. The work of the Centre was found to illustrate many aspects of best practice but also raised questions worthy of future exploration. The current article reports on overall cultural appropriateness, particularly identifying barriers which may inhibit access and how acculturation may play a role in reducing perception of barriers. An earlier article reported on access, retention and outcomes for these CALD groups (Akin Ojelabi et al., 2011).