Lipidome of mammographic breast density in premenopausal women

BACKGROUND: High mammographic breast density (MBD) is a strong risk factor for breast cancer development, but the biological mechanisms underlying MBD are unclear. Lipids play important roles in cell differentiation, and perturbations in lipid metabolism are implicated in cancer development. Nevertheless, no study has applied untargeted lipidomics to profile the lipidome of MBD. Through this study, our goal is to characterize the lipidome of MBD in premenopausal women. METHODS: Premenopausal women were recruited during their annual screening mammogram at the Washington University School of Medicine in St. Louis, MO. Untargeted lipidomic profiling for 982 lipid species was performed at Metabolon (Durham, NC®), and volumetric measures of MBD (volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)) was assessed using Volpara 1.5 (Volpara Health®). We performed multivariable linear regression models to investigate the associations of lipid species with MBD and calculated the covariate-adjusted least square mean of MBD by quartiles of lipid species. MBD measures were log RESULTS: Of the 705 premenopausal women, 72% were non-Hispanic white, and 23% were non-Hispanic black. Mean age, and BMI were 46 years and 30 kg/m CONCLUSIONS: We report novel lipid species that are associated with MBD in premenopausal women. Studies are needed to validate our results and the translational potential

Disease and the Dynamics of Food Webs

What models and statistical tools can best help us assess how ecosystems respond to the impact of multiple factors, such as disease, predation, fire, and rain

A Review of Web-Based Job Advertisements for Australian Event Management Positions

Strong growths in the Australian event management industry, ongoing technological changes and the internationalisation of the market place has spurred the need for appropriately educated and trained event managers and for a re-evaluation of educational and job training curriculum to meet these new challenges. In order for Australia to position itself as a world leader in event management, it is important to provide consistent high professional standards and event managers that not only meet, but exceed the demands of the industry. While there is some literature that focuses on the tourism and leisure job market (Crossley, 1992; Keung & Pine, 2000), and a small but developing literature base that focuses on event management training (Harris & Jago, 1999; Hawkins & Goldbatt, 1995) relatively little consideration has been given to a national agenda for event management skilling. To provide an indication of current employer requirements, a nationwide study of job advertisements in event management has commenced. The aims of the study are to further the understanding of the educational needs and training requirements of the industry; to ascertain the learned skills and personal attributes sought from event managers; to determine the compatibility of industry demands with current educational and vocational provisions; and to suggest post-secondary institutional avenues through which event management education and training needs can be pursued. This is an ongoing study and it is hoped that it will contribute towards a broad scale understanding of the event management job market. More importantly however, it can be used as the basis for curriculum evaluation and training needs, and create a better understanding and compatibility between event management education and industry practice. This paper reports the preliminary results from a content analysis of approximately 100 web-based job advertisements. Email alert accounts were established with several search engines to gather a sample of event management related job advertisements from around Australia. An analytical framework was devised for the analysis of the advertisements themselves. The results reveal several interesting trends including the geographical concentration of the event management job market, the range of industries that require event management specialists or event management skills, and a series of required skills and key attributes of event managers. The results of this study establish a platform from which to develop a classification of event management skills required by the industry

Family history of cancer and head and neck cancer survival

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137774/1/lary26524_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137774/2/lary26524.pd

Sport in the city: measuring economic significance at the local level

In many cities throughout Europe, sport is increasingly being used as a tool for economic revitalisation. While there has been a growth in literature relating to the specific economic impacts of sports-led development, including professional sport facilities, teams, and sport events, limited research has been undertaken on the contribution of the whole sport sector to output and employment. In the United Kingdom (UK), studies have focused on evaluating sport-related economic activity at the national level, yet despite the increasing use of sport for local economic development little research has been undertaken at the city level. To address this situation, this article uses the National Income Accounting framework to measure the economic importance of sport in Sheffield, UK. It shows that the value-added in 1996/97 was 165.61m or 4.11% of Gross Domestic Product (GDP), approximately twice the amount predicted from current national estimates. It is argued that this can primarily be explained by previous studies under-estimating the economic importance of sport, largely due to methodological differences. It goes on to suggest that future research on the significance of sport should be undertaken at the local level to provide policymakers with information at the spatial level where regeneration programmes are being implemented.</p

Expression profiles of acute lymphoblastic and myeloblastic leukemias with ALL-1 rearrangements

The ALL-1 gene is directly involved in 5-10% of ALLs and AMLs by fusion to other genes or through internal rearrangements. DNA microarrays were utilized to determine expression profiles of ALLs and AMLs with ALL-1 rearrangements. These profiles distinguish those tumors from other ALLs and AMLs. The expression patterns of ALL-1-associated tumors, in particular ALLs, involve oncogenes, tumor suppressors, anti apoptotic genes, drug resistance genes etc., and correlate with the aggressive nature of the tumors. The genes whose expression differentiates between ALLs with and without ALL-1 rearrangement were further divided into several groups enabling separation of ALL-1- associated ALLs into two subclasses. Further, AMLs with partial duplication of ALL-1 vary in their expression pattern from AMLs in which ALL-1 had undergone fusion to other genes. The extensive analysis described here draws attention to genes which might have a direct role in pathogenesis

Modeling genomic diversity and tumor dependency in malignant melanoma

The classification of human tumors based on molecular criteria offers tremendous clinical potential; however, discerning critical and "druggable" effectors on a large scale will also require robust experimental models reflective of tumor genomic diversity. Here, we describe a comprehensive genomic analysis of 101 melanoma short-term cultures and cell lines. Using an analytic approach designed to enrich for putative "driver" events, we show that cultured melanoma cells encompass the spectrum of significant genomic alterations present in primary tumors. When annotated according to these lesions, melanomas cluster into subgroups suggestive of distinct oncogenic mechanisms. Integrating gene expression data suggests novel candidate effector genes linked to recurrent copy gains and losses, including both phosphatase and tensin homologue (PTEN)-dependent and PTEN-independent tumor suppressor mechanisms associated with chromosome 10 deletions. Finally, sample-matched pharmacologic data show that FGFR1 mutations and extracellular signal-regulated kinase (ERK) activation may modulate sensitivity to mitogen-activated protein kinase/ERK kinase inhibitors. Genetically defined cell culture collections therefore offer a rich framework for systematic functional studies in melanoma and other tumors

Planning and Leveraging Event Portfolios: Towards a Holistic Theory

This conceptual paper seeks to advance the discourse on the leveraging and legacies of events by examining the planning, management, and leveraging of event portfolios. This examination shifts the common focus from analyzing single events towards multiple events and purposes that can enable cross-leveraging among different events in pursuit of attainment and magnification of specific ends. The following frameworks are proposed: (1) event portfolio planning and leveraging, and (2) analyzing events networks and inter-organizational linkages. These frameworks are intended to provide, at this infancy stage of event portfolios research, a solid ground for building theory on the management of different types and scales of events within the context of a portfolio aimed to obtain, optimize and sustain tourism, as well as broader community benefits

Priority setting in primary health care - dilemmas and opportunities: a focus group study

<p>Abstract</p> <p>Background</p> <p>Swedish health care authorities use three key criteria to produce national guidelines for local priority setting: severity of the health condition, expected patient benefit, and cost-effectiveness of medical intervention. Priority setting in primary health care (PHC) has significant implications for health costs and outcomes in the health care system. Nevertheless, these guidelines have been implemented to a very limited degree in PHC. The objective of the study was to qualitatively assess how general practitioners (GPs) and nurses perceive the application of the three key priority-setting criteria.</p> <p>Methods</p> <p>Focus groups were held with GPs and nurses at primary health care centres, where the staff had a short period of experience in using the criteria for prioritising in their daily work.</p> <p>Results</p> <p>The staff found the three key priority-setting criteria (severity, patient benefit, and cost-effectiveness) to be valuable for priority setting in PHC. However, when the criteria were applied in PHC, three additional dimensions were identified: 1) viewpoint (medical or patient's), 2) timeframe (now or later), and 3) evidence level (group or individual).</p> <p>Conclusions</p> <p>The three key priority-setting criteria were useful. Considering the three additional dimensions might enhance implementation of national guidelines in PHC and is probably a prerequisite for the criteria to be useful in priority setting for individual patients.</p

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120