Identification of evidence-based biospecimen quality-control tools

Control of biospecimen quality that is linked to processing is one of the goals of biospecimen science. Consensus is lacking, however, regarding optimal sample quality-control (QC) tools (ie, markers and assays). The aim of this review was to identify QC tools, both for fluid and solid-tissue samples, based on a comprehensive and critical literature review. The most readily applicable tools are those with a known threshold for the preanalytical variation and a known reference range for the QC analyte. Only a few meaningful markers were identified that meet these criteria, such as CD40L for assessing serum exposure at high temperatures and VEGF for assessing serum freeze-thawing. To fully assess biospecimen quality, multiple QC markers are needed. Here we present the most promising biospecimen QC tools that were identified.

Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

New and young firms Entrepreneurship policy and the role of government – evidence from the Federation of Small Businesses survey

Purpose – The purpose of this paper is to investigate whether new and young firms are different from older firms. This analysis is undertaken to explore general characteristics, use of external resources and growth orientation. Design/methodology/approach – Data from the 2008 UK Federation of Small Businesses survey provided 8,000 responses. Quantitative analysis identified significantly different characteristics of firms from 0-4, 4-9, 9-19 and 20+ years. Factor analysis was utilised to identify the advice sets, finance and public procurement customers of greatest interest, with ANOVA used to statistically compare firms in the identified age groups with different growth aspirations. Findings – The findings reveal key differences between new, young and older firms in terms of characteristics including business sector, owner/manager age, education/business experience, legal status, intellectual property and trading performance. New and young firms were more able to access beneficial resources in terms of finance and advice from several sources. New and young firms were also able to more easily access government and external finance, as well as government advice, but less able to access public procurement. Research limitations/implications – New and young firms are utilising external networks to access several resources for development purposes, and this differs for older firms. This suggests that a more explicit age-differentiated focus is required for government policies aimed at supporting firm growth. Originality/value – The study provides important baseline data for future quantitative and qualitative studies focused on the impact of firm age and government policy.

Unpacking user relations in an emerging ubiquitous computing environment : introducing the bystander

The move towards technological ubiquity is allowing a more idiosyncratic and dynamic working environment to emerge that may result in the restructuring of information communication technologies, and changes in their use through different user groups' actions. Taking a ‘practice’ lens to human agency, we explore the evolving roles of, and relationships between these user groups and their appropriation of emergent technologies by drawing upon Lamb and Kling's social actor framework. To illustrate our argument, we draw upon a study of a UK Fire Brigade that has introduced a variety of technologies in an attempt to move towards embracing mobile and ubiquitous computing. Our analysis of the enactment of such technologies reveals that Bystanders, a group yet to be taken as the central unit of analysis in information systems research, or considered in practice, are emerging as important actors. The research implications of our work relate to the need to further consider Bystanders in deployments other than those that are mobile and ubiquitous. For practice, we suggest that Bystanders require consideration in the systems development life cycle, particularly in terms of design and education in processes of use.

The micro-movie wave in a globalising China : adaptation, formalisation and commercialisation

While user-generated short online videos have existed since the emergence of video sharing sites in China, they have undergone a process of formalisation and commercialisation, culminating in the wave of micro-movies in recent years. By addressing the wider context of globalisation alongside relevant state policies and shifting viewing habits, this article analyses the local and global causes of this wave. It offers evidence that illustrates how online video service providers in China have adapted in a changing industry landscape as they negotiate state policies, advertiser interests and user preference. It then examines the production and distribution dynamics, where professional producers draw on social media, grassroots creativity and creative talents in regional markets. Finally, it discusses the cultural implications of this process in terms of both the nature and flow of creativity. Based on these analyses, the article also sheds light on the interplay between the state and the market in the context of globalisation and marketisation of media sectors, which becomes more complicated when the state-owned or controlled media enter the emerging market sectors.

Patient Safety Law: From Silos to Systems

Patient safety has become a significant and pressing policy issue. Around the world, governments, the health care sector and the public are increasingly cognizant of the need to improve the safety of care delivered by their health systems. Pressure for change has been created by highly publicized incidents in a number of countries involving unsafe acts that were significant both in scale and consequence and a number of empirical studies that revealed the high rates of unsafe acts and their consequences. The costs of unsafe health care – both personal and fiscal – to individuals, their families and their communities and to the state are massive. In this research project we explored one particular avenue for change – that is, the use of legal instruments by governments to improve patient safety. We did this through a comparative review of the use of legal instruments or frameworks in other countries (specifically Australia, Denmark, New Zealand, the United Kingdom, and the United States) as well as two non-health care related sectors in Canada (transportation and occupational health and safety). We began this research by reviewing the legal instruments and undertaking extensive literature reviews. Further information was gathered through in-person interviews with policy-makers and academics in the countries studied, and from policy-makers and academics expert in the health, occupational health and safety, and transportation sectors in Canada. Once descriptions of the various countries and sectors were drafted, we held small-group meetings with local experts on particular aspects of patient safety. We then hosted a national consultation meeting. We subsequently drafted this final report and the appendices, which fully describe the results of the background research. Finally, we prepared a summary version of the report as well as posters and papers to be published and delivered at conferences and meetings with relevant groups.

Community college faculty's teaching social networks and their implications for librarians

Collaboration between faculty and librarians is an important topic of discussion and research among academic librarians. These partnerships between faculty and librarians are vital for enabling students to become lifelong learners through their information literacy education. This research developed an understanding of academic collaborators by analyzing a community college faculty's teaching social networks. A teaching social network, an original term generated in this study, is comprised of communications that influence faculty when they design and deliver their courses. The communication may be formal (e.g., through scholarly journals and professional development activities) and informal (e.g., through personal communication) through their network elements. Examples of the elements of a teaching social network may be department faculty, administration, librarians, professional development, and students. This research asked 'What is the nature of faculty's teaching social networks and what are the implications for librarians?' This study moves forward the existing research on collaboration, information literacy, and social network analysis. It provides both faculty and librarians with added insight into their existing and potential relationships. This research was undertaken using mixed methods. Social network analysis was the quantitative data collection methodology and the interview method was the qualitative technique. For the social network analysis data, a survey was sent to full-time faculty at Las Positas College, a community college, in California. The survey gathered the data and described the teaching social networks for faculty with respect to their teaching methods and content taught. Semi-structured interviews were conducted following the survey with a sub-set of survey respondents to understand why specific elements were included in their teaching social networks and to learn of ways for librarians to become an integral part of the teaching social networks. The majority of the faculty respondents were moderately influenced by the elements of their network except the majority of the potentials were weakly influenced by the elements in their network in their content taught. The elements with the most influence on both teaching methods and content taught were students, department faculty, professional development, and former graduate professors and coursework. The elements with the least influence on both aspects were public or academic librarians, and social media. The most popular roles for the elements were conversations about teaching, sharing ideas, tips for teaching, insights into teaching, suggestions for ways of teaching, and how to engage students. Librarians' weakly influenced faculty in their teaching methods and their content taught. The motivating factors for collaboration with librarians were that students learned how to research, students' research projects improved, faculty saved time by having librarians provide the instruction to students, and faculty built strong working relationships with librarians. The challenges of collaborating with librarians were inadequate teaching techniques used when librarians taught research orientations and lack of time. Ways librarians can be more integral in faculty's teaching social networks included: more workshops for faculty, more proactive interaction with faculty, and more one-on-one training sessions for faculty. Some of the recommendations for the librarians from this study were develop a strong rapport with faculty, librarians should build their services in information literacy from the point of view of the faculty instead of from the librarian perspective, use staff development funding to attend conferences and workshops to improve their teaching, develop more training sessions for faculty, increase marketing efforts of the librarian's instructional services, and seek grant opportunities to increase funding for the library. In addition, librarians and faculty should review the definitions of information literacy and move from a skills based interpretation to a learning process.

Standard preanalytical coding for biospecimens: Review and implementation of the Sample PREanalytical Code (SPREC)

The first version of the Standard PREanalytical Code (SPREC) was developed in 2009 by the International Society for Biological and Environmental Repositories (ISBER) Biospecimen Science Working Group to facilitate documentation and communication of the most important preanalytical quality parameters of different types of biospecimens used for research. This same Working Group has now updated the SPREC to version 2.0, presented here, so that it contains more options to allow for recent technological developments. Existing elements have been fine tuned. An interface to the Biospecimen Reporting for Improved Study Quality (BRISQ) has been defined, and informatics solutions for SPREC implementation have been developed. A glossary with SPRECrelated definitions has also been added.

Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1P29S) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1P29S showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer

Background: Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease. Methods: TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB 2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression. Results: TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB 2levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis. Conclusion: TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC. © 2011 Cathcart et al; licensee BioMed Central Ltd.

Prostacyclin synthase expression and epigenetic regulation in nonsmall cell lung cancer

BACKGROUND: Prostacyclin synthase (PGIS) metabolizes prostaglandin H(2), into prostacyclin. This study aimed to determine the expression profile of PGIS in nonsmall cell lung cancer (NSCLC) and examine potential mechanisms involved in PGIS regulation. METHODS: PGIS expression was examined in human NSCLC and matched controls by reverse transcriptase polymerase chain reaction (RT-PCR), Western analysis, and immunohistochemistry. A 204-patient NSCLC tissue microarray was stained for PGIS and cyclooxygenase 2 (COX2) expression. Staining intensity was correlated with clinical parameters. Epigenetic mechanisms underpinning PGIS promoter expression were examined using RT-PCR, methylation-specific PCR, and chromatin immunoprecipitation analysis. RESULTS: PGIS expression was reduced/absent in human NSCLC protein samples (P <.0001), but not mRNA relative to matched controls. PGIS tissue expression was higher in squamous cell carcinoma (P =.004) and in male patients (P <.05). No significant correlation of PGIS or COX2 expression with overall patient survival was observed, although COX2 was prognostic for short-term (2-year) survival (P <.001). PGIS mRNA expression was regulated by DNA CpG methylation and histone acetylation in NSCLC cell lines, with chromatin remodeling taking place directly at the PGIS gene. PGIS mRNA expression was increased by both demethylation agents and histone deacetylase inhibitors. Protein levels were unaffected by demethylation agents, whereas PGIS protein stability was negatively affected by histone deacetylase inhibitors. CONCLUSIONS: PGIS protein expression is reduced in NSCLC, and does not correlate with overall patient survival. PGIS expression is regulated through epigenetic mechanisms. Differences in expression patterns between mRNA and protein levels suggest that PGIS expression and protein stability are regulated post-translationally. PGIS protein stability may have an important therapeutic role in NSCLC. © 2011 American Cancer Society.

A survey of the Queensland healthcare workforce : attitudes towards dementia care and training

Background Positive attitudes of healthcare staff towards people with dementia promote higher quality care, although little is known about important factors that underlie positive attitudes. Key aims of this project were to explore the relationships between staff attitudes towards dementia, self-confidence in caring for people with dementia, experience and dementia education and training. Method A brief online survey was developed and widely distributed to registered nurses and allied health professionals working in Queensland in 2012. Regression analyses were performed to identify important predictors of self-confidence in caring for people with dementia and positive attitudes towards people with dementia. Results Five hundred and twenty-four surveys were completed by respondents working in a range of care settings across Queensland. Respondents were predominantly female (94.1%), and most were registered nurses (60%), aged between 41 and 60 years (65.6%). Around 40% regularly worked with people with dementia and high levels of self-confidence in caring for this population and positive attitudes towards people with dementia were reported. The majority of respondents (67%) had participated in a dementia education/training activity in the past 12 months. More experience working with people with dementia predicted greater self-confidence while recent participation in a dementia education/training and higher self-confidence in caring for a person with dementia significantly predicted more positive attitudes towards people with dementia. Conclusion These results confirm the importance of self-confidence and dementia education in fostering positive attitudes and care practices towards people with dementia. Our results also indicate that the demand for ongoing dementia education is high amongst health care workers and it is recommended that regular dementia education/ training be provided and promoted for all healthcare personnel who work with people with dementia.

Differentiation of isomeric N-glycan structures by normal-phase liquid chromatography-MALDI-TOF/TOF tandem mass spectrometry

The detailed characterization of protein N-glycosylation is very demanding given the many different glycoforms and structural isomers that can exist on glycoproteins. Here we report a fast and sensitive method for the extensive structure elucidation of reducing-end labeled N-glycan mixtures using a combination of capillary normal-phase HPLC coupled off-line to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and TOF/TOF-MS/MS. Using this method, isobaric N-glycans released from honey bee phospholipase A2 and Arabidopsis thaliana glycoproteins were separated by normal-phase chromatography and subsequently identified by key fragment ions in the MALDI-TOF/TOF tandem mass spectra. In addition, linkage and branching information were provided by abundant cross-ring and "elimination" fragment ions in the MALDI-CID spectra that gave extensive structural information. Furthermore, the fragmentation characteristics of N-glycans reductively aminated with 2-aminobenzoic acid and 2-aminobenzamide were compared. The identification of N-glycans containing 3-linked core fucose was facilitated by distinctive ions present only in the MALDI-CID spectra of 2-aminobenzoic acid-labeled oligosaccharides. To our knowledge, this is the first MS/MS-based technique that allows confident identification of N-glycans containing 3-linked core fucose, which is a major allergenic determinant on insect and plant glycoproteins.