Speckle-type POZ protein mutations interrupt tumor suppressor function of speckle-type POZ protein in prostate cancer by affecting androgen receptor degradation

Large scale exome sequencing studies have revealed regions of the genome, which contribute to the castrate resistant prostate cancer (CRPC) phenotype. [1],[2],[3] Such studies have identified mutations in genes, which may have diagnostic/prognostic potential, or which may be targeted therapeutically. Two of these genes include the androgen receptor (AR) and speckle-type POZ protein (SPOP) genes. However, the findings from these exome sequencing studies can only be translated therapeutically once the functional consequences of these mutations have been determined. Here, we highlight the recent study by An et al. [4] which investigated the functional effects of mutations in the SPOP gene that were identified in the aforementioned exome sequencing studies, particularly in the context of SPOP-mediated degradation of the AR.

The use of penumbrae to define and analyse non-standard fields

Aim A new method of penumbral analysis is implemented which allows an unambiguous determination of field size and penumbra size and quality for small fields and other non-standard fields. Both source occlusion and lateral electronic disequilibrium will affect the size and shape of cross-axis profile penumbrae; each is examined in detail. Method A new method of penumbral analysis is implemented where the square of the derivative of the cross-axis profile is plotted. The resultant graph displays two peaks in the place of the two penumbrae. This allows a strong visualisation of the quality of a field penumbra, as well as a mathematically consistent method of determining field size (distance between the two peak’s maxima), and penumbra (full-widthtenth-maximum of peak). Cross-axis profiles were simulated in a water phantom at a depth of 5 cm using Monte Carlo modelling, for field sizes between 5 and 30 mm. The field size and penumbra size of each field was calculated using the method above, as well as traditional definitions set out in IEC976. The effect of source occlusion and lateral electronic disequilibrium on the penumbrae was isolated by repeating the simulations removing electron transport and using an electron spot size of 0 mm, respectively. Results All field sizes calculated using the traditional and proposed methods agreed within 0.2 mm. The penumbra size measured using the proposed method was systematically 1.8 mm larger than the traditional method at all field sizes. The size of the source had a larger effect on the size of the penumbra than did lateral electronic disequilibrium, particularly at very small field sizes. Conclusion Traditional methods of calculating field size and penumbra are proved to be mathematically adequate for small fields. However, the field size definition proposed in this study would be more robust amongst other nonstandard fields, such as flattening filter free. Source occlusion plays a bigger role than lateral electronic disequilibrium in small field penumbra size.

Ethnic cluster lifecycle : a case of Chinese restaurants in South East Queensland

Immigrant entrepreneurs tend to start businesses within their ethnic enclave (EE), as it is an integral part of their social and cultural context and the location where ethnic resources reside (Logan, Alba, & Stults, 2003). Ethnic enclaves can be seen as a form of geographic cluster, China Towns are exemplar EEs, easily identified by the clustering of Chinese restaurants and other ethnic businesses in one central location. Studies on EE thus far have neglected the life cycles stages of EE and its impact on the business experiences of the entrepreneurs. In this paper, we track the formation, growth and decline of an EE. We argue that EE is a special industrial cluster and as such it follows the growth conditions proposed by the cluster life cycle theory (Menzel & Fornahl, 2009). We report a mixed method study of Chinese Restaurants in South East Queensland. Based on multiple sources of data, we concluded that changes in government policies leading to a sharp increase of immigrant numbers from a distinctive culture group can lead to the initiation and growth of the EE. Continuous incoming of new immigrants and increase competition within the cluster mark the mature stage of the EE, making the growth condition more favourable “inside” the cluster. A decline in new immigrants from the same ethnic group and the increased competition within the EE may eventually lead to the decline of such an industrial cluster, thus providing more favorable condition for growth of business outside the cluster.

Sans Faute

Sans Faute (without fail) considers how technology has influenced Chinese society, culture and practice. The exhibition seeks to reveal a shared language between Western and Chinese contexts that exists through employing technology as a universal creative meeting point. The pervasive impact of the current digital landscape has been widely recognised, embraced and continues to influence many aspects of Chinese lives. The significance of these shifting contexts on contemporary art is explored in Sans Faute. Through the presentation of a range of video installations, the exhibition aims to initiate rigorous and critical engagement with these provocative works that challenge traditional ideologies to discover emergent ideas. Featuring works by eight artists from mainland China, Sans Faute is an exploration of different attitudes collected together to provide a complete picture of how these artists build a new iconic imagery. "The works of these artists present a younger generation's thinking of the reality of contemporary China through their own emotional and individual life experience," says Stephen Danzig, IDAprojects director. "We are currently witnessing an amazing re-identification in so many elements that make up China's social fabric - none more so than what's happening in the arts currently. You only need to see what's happening in Beijing to realise the pace of change." Sans Faute has been supported by QUT Confucius Institute.

Paired back

Paired Back (2013) investigated the interpretation of text as a dance score. Specific words were used to trigger movement sequences. The performers, Avril Huddy and Jenny Roche, responded to spoken words with individual movement responses which were captured on video, reviewed and assembled as a duet. The musician Nicholas Ng, playing traditional Chinese instruments was also woven into the dancers’ choreography. This was achieved through choreographing a floor pattern that enabled him to weave through the space and ‘seemingly’ interact with the dancers’ actions. Projections using motion capture were also explored and sequenced with the actions of the dance. Retrospectively, I recognised my ‘intuitive’ use of text which I have mapped from its beginnings during the first rehearsal through to the performance at the Judith Wright Centre and demonstrated in DVD documentation. Consequently traces of this original ‘score’ used during the creative process are visible in final performance outcome. This has enabled me to reflect on the impact of language and instructions within my creative process.

Perception of prescription medicine sample packs among Australian professional, government, industry, and consumer organizations, based on automated textual analysis of one-on-one interviews

Background Prescription medicine samples provided by pharmaceutical companies are predominantly newer and more expensive products. The range of samples provided to practices may not represent the drugs that the doctors desire to have available. Few studies have used a qualitative design to explore the reasons behind sample use. Objective The aim of this study was to explore the opinions of a variety of Australian key informants about prescription medicine samples, using a qualitative methodology. Methods Twenty-three organizations involved in quality use of medicines in Australia were identified, based on the authors' previous knowledge. Each organization was invited to nominate 1 or 2 representatives to participate in semistructured interviews utilizing seeding questions. Each interview was recorded and transcribed verbatim. Leximancer v2.25 text analysis software (Leximancer Pty Ltd., Jindalee, Queensland, Australia) was used for textual analysis. The top 10 concepts from each analysis group were interrogated back to the original transcript text to determine the main emergent opinions. Results A total of 18 key interviewees representing 16 organizations participated. Samples, patient, doctor, and medicines were the major concepts among general opinions about samples. The concept drug became more frequent and the concept companies appeared when marketing issues were discussed. The Australian Pharmaceutical Benefits Scheme and cost were more prevalent in discussions about alternative sample distribution models, indicating interviewees were cognizant of budgetary implications. Key interviewee opinions added richness to the single-word concepts extracted by Leximancer. Conclusions Participants recognized that prescription medicine samples have an influence on quality use of medicines and play a role in the marketing of medicines. They also believed that alternative distribution systems for samples could provide benefits. The cost of a noncommercial system for distributing samples or starter packs was a concern. These data will be used to design further research investigating alternative models for distribution of samples.

Community pharmacy dispensing of prescription medicine sample packs: Changing the business of medicine initiation?

Prescription medicine samples (or starter packs) are provided by pharmaceutical manufacturers to prescribing doctors as one component in the suite of marketing products used to convince them to prescribe a particular medicine [1,2]. Samples are generally newer, more expensive treatment options still covered by patent [3,4]. Safe, effective, judicious and appropriate medicine use (quality use of medicines) [5] could be enhanced by involving community pharmacists in the dispensing of starter packs. Doctors who use samples show a trend towards prescribing more expensive medicines overall [6] and also prescribe more medicines [7]. Cardiovascular health and mental health are Australian National Health Priority Areas [8] and account for approximately 30% and 17%, respectively, of annual government Pharmaceutical Benefits System (PBS) in 2006 [9]. The PBS is Australia's universal prescription subsidy scheme [9]. Antihypertensives were a major contributor to the estimated 80 000 medicine-related hospital admissions in Australia in 1999 [10] and also internationally [11,12]. The aim of this study was to pilot an alternative model for supply of free sample or starter packs of prescription medicines and ascertain if it is a viable model in daily practice.

Chinese EFL students' response to an assessment policy change

In light of its documented potential for enhancing learning, formative assessment has been adopted across a range of educational contexts to improve the quality of education. The assessment innovation that the Chinese Ministry of Education (CMoE) proposed to College English in 2007 via the College English Curriculum Requirements (CECR) (CMoE, 2007), is an initiative of this kind. Considering the acknowledged influence of assessment on students’ learning, it is instructive to explore the ways in which Chinese university students respond to an assessment policy change of this magnitude, particularly as it positions them as more active learners, having the potential for increased agency and engagement in their English language learning and assessment practices. In order to explore the response of students to this assessment initiative, a case study was conducted in the context of a College English classroom. Data included an interview with a College English teacher and four students from her classes, and classroom observations and a survey of her two classes of 100 students. Analysis of the data reveals that Chinese students’ responses to the assessment policy change are influenced by a variety of sociocultural factors, including their previous English language learning and assessment experience and the extent to which they are willing to play the ‘assessment game’. These findings have implications for policy and practice.

The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals : consequences for occupational and environmental medicine

The importance of the isoform CYP2E1 of the human cytochrome P-450 superfamily of enzymes for occupational and environmental medicine is derived from its unique substrate spectrum that includes a number of highly important high-production chemicals, such as aliphatic and aromatic hydrocarbons, solvents and industrial monomers (i.a. alkanes, alkenes, aromatic and halogenated hydrocarbons). Many polymorphic genes, such as CYP2E1, show considerable differences in allelic distribution between different human populations. The polymorphic nature of the human CYP2E1 gene is significant for inter-individual differences in toxicity of its substrates. Since the substrate spectrum of CYP2E1 includes many compounds of basic relevance to industrial toxicology, a rationale for metabolic interactions of different CYP2E1 substrates is provided. In-depth research into the inter-individual phenotypic differences of human CYP2E1 enzyme activities was enabled by the recognition that the 6-hydroxylation of the drug chlorzoxazone is mediated by CYP2E1. Studies on CYP2E1 phenotyping have pointed to inter-individual variations in enzyme activities. There are consistent ethnic differences in CYP2E1 enzyme expression, mostly demonstrated between European and Japanese populations, which point to a major impact of genetic factors. The most frequently studied genetic polymorphisms are the restriction fragment length polymorphisms PstI/RsaI (mutant allele: CYP2E1*5B) located in the 5′-flanking region of the gene, as well as the DraI polymorphism (mutant allele: CYP2E1*6) located in intron 6. These polymorphisms are partly related, as they form the common allele designated CYP2E1*5A. Striking inter-ethnic differences between Europeans and Asians appear with respect to the frequencies of the CYP2E1*5A allele (only approximately 5% of Europeans are heterozygous, but 37% of Asians are, whilst 6% of Asians are homozygous). Available studies indicate a wide variation in human CYP2E1 expression, which are very likely based on complex gene-environment interactions. Major inter-ethnic differences are apparent on the genotyping and the phenotyping levels. Selected cases are presented where inter-ethnic variations of CYP2E1 may provide likely explanations for unexplained findings concerning industrial chemicals that are CYP2E1 substrates. Possible consequences of differential inter-individual and inter-ethnic susceptibilities are related to individual expressions of clinical symptoms of chemical toxicity, to results of biological monitoring of exposed workers, and to the interpretation of results of epidemiological or molecular-epidemiological studies.

European aspects of standard setting in occupational hygiene and medicine

Occupational standards concerning the allowable concentrations of chemical compounds in the ambient air of workplaces have been established in several countries at national levels. With the integration of the European Union, a need exists for establishing harmonized Occupational Exposure Limits. For analytical developments, it is apparent that methods for speciation or fractionation of carcinogenic metal compounds will be of increasing practical importance for standard setting. Criteria of applicability under field conditions, cost-effectiveness, and robustness are practical driving forces for new developments. When the European Union issued a list of 62 chemical substances with Occupational Exposure Limits in 2000, 25 substances received a 'skin' notation. The latter indicates that toxicologically significant amounts may be taken up via the skin. Similar notations exist on national levels. For such substances, monitoring concentrations in ambient air will not be sufficient; biological monitoring strategies will gain further importance in the medical surveillance of workers who are exposed to such compounds. Proceedings in establishing legal frameworks for a biological monitoring of chemical exposures within Europe are paralleled by scientific advances in this field. A new aspect is the possibility of a differential adduct monitoring, using blood proteins of different half-life or lifespan. This technique allows differentiation between long-term mean exposure to reactive chemicals and short-term episodes, for example, by accidental overexposure. For further analytical developments, the following issues have been addressed as being particularly important: New dose monitoring strategies, sensitive and reliable methods for detection of DNA adducts, cytogenetic parameters in biological monitoring, methods to monitor exposure to sensitizing chemicals, and parameters for individual susceptibilities to chemical toxicants.

Self-efficacy moderation and mediation roles on BPSD and social support influences on subjective caregiver burden in Chinese spouse caregivers of dementia patients

Background: This study aims to explore moderation and mediation roles of caregiver self-efficacy between subjective caregiver burden and (a) behavioral and psychological symptoms (BPSD) of dementia; and (b) social support. Methods: A cross-sectional study with 137 spouse caregivers of dementia patients was conducted in Shanghai. We collected demographic information for the caregiver–patient dyads, as well as information associated with dementia-related impairments, caregiver social support, caregiver self-efficacy, and SF-36. Results: Multiple regression analysis showed that caregiver self-efficacy was a moderator both between BPSD and subjective caregiver burden, and social support and subjective caregiver burden. Results also showed a partial mediation effect of caregiver self-efficacy on the impact of BPSD on subjective caregiver burden, and a mediation effect of social support on subjective caregiver burden. Caregiver self-efficacy and subjective burden significantly influenced BPSD and social support. Conclusion: Caregiver self-efficacy played an important role in the paths by which the two factors influenced subjective burden. Enhancing caregiver self-efficacy for symptom management (particularly BPSD) can be an essential strategy for determining interventions to support dementia caregivers in China, and possibly in other countries.