The genetics of endurance : frequency of the ACTN3 R577X variant in Ironman World Championship athletes

Objectives To investigate the frequency of the ACTN3 R577X polymorphism in elite endurance triathletes, and whether ACTN3 R577X is significantly associated with performance time. Design Cross-sectional study. Methods Saliva samples, questionnaires, and performance times were collected for 196 elite endurance athletes who participated in the 2008 Kona Ironman championship triathlon. Athletes were of predominantly North American, European, and Australian origin. A one-way analysis of variance was conducted to compare performance times between genotype groups. Multiple linear regression analysis was performed to model the effect of questionnaire variables and genotype on performance time. Genotype and allele frequencies were compared to results from different populations using the chi-square test. Results Performance time did not significantly differ between genotype groups, and age, sex, and continent of origin were significant predictors of finishing time (age and sex: p < 5 × 10−6; continent: p = 0.003) though genotype was not. Genotype and allele frequencies obtained (RR 26.5%, RX 50.0%, XX 23.5%, R 51.5%, X 48.5%) were found to be not significantly different from Australian, Spanish, and Italian endurance athletes (p > 0.05), but were significantly different from Kenyan, Ethiopian, and Finnish endurance athletes (p < 0.01). Conclusions Genotype and allele frequencies agreed with those reported for endurance athletes of similar ethnic origin, supporting previous findings for an association between 577X allele and endurance. However, analysis of performance time suggests that ACTN3 does not alone influence endurance performance, or may have a complex effect on endurance performance due to a speed/endurance trade-off.

Reliability and validity of conjunctival ultraviolet autofluorescence measurement

BACKGROUND: Conjunctival ultraviolet autofluorescence (UVAF) photography was developed to detect and characterise pre-clinical sunlight-induced UV damage. The reliability of this measurement and its relationship to outdoor activity are currently unknown. METHODS: 599 people aged 16-85 years in the cross-sectional Norfolk Island Eye Study were included in the validation study. 196 UVAF individual photographs (49 people) and 60 UVAF photographs (15 people) of Norfolk Island Eye Study participants were used for intra- and inter-observer reliability assessment, respectively. Conjunctival UVAF was measured using UV photography. UVAF area was calculated using computerised methods by one grader on two occasions (intra-observer analysis) or two graders (inter-observer analysis). Outdoor activity category, during summer and winter separately, was determined with a UV questionnaire. Total UVAF equalled the area measured in four conjunctival areas (nasal/temporal conjunctiva of right and left eyes). RESULTS: Intra-observer (ρ_c=0.988, 95% CI 0.967 to 0.996, p<0.001), and inter-observer concordance correlation coefficients (ρ_c=0.924, 95% CI 0.870 to 0.956, p<0.001) of total UVAF exceeded 0.900. When grouped according to 10 mm(2) total UVAF increments, intra- and inter-observer reliability was very good (κ=0.81) and good (κ=0.71), respectively. Increasing time outdoors was strongly with increasing total UVAF in summer and winter (p(trend) <0.001). CONCLUSION: Intra- and inter-observer reliability of conjunctival UVAF is high. In this population, UVAF correlates strongly with the authors' survey-based assessment of time spent outdoors.

Platelet-derived endothelial cell growth factor (thymidine phosphorylase) expression in lung cancer

Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is an enzyme with angiogenic and cell motility properties. Moreover, it is involved in the transformation of fluoropyrimidines into active cytotoxic metabolites, In the present study, the expression of PD-ECGF in normal lung and lung cancer was immunohistochemically evaluated using the P-GF.44C monoclonal antibody. Alveolar and tumoural macrophages mere invariably stained and mere used as an internal control for assessment of the staining. Alveolar epithelium was always negative, whilst bronchiolar epithelium showed occasional positive reactivity. Normal lung and tumour endothelium was occasionally positive, Positive staining in more than 50 per cent of cells was observed in 23/71 squamous carcinomas (32 per cent), 16/38 (42 per cent) adenocarcinomas, and 2/6 (33 per cent) adenosquamous carcinomas. Differentiated areas and areas of squamous metaplasia mere more strongly positive than other tumour areas. All 22 small cell carcinomas and one carcinoid tumour were negative. The present study provides a baseline for future studies in non-small cell lung cancer to correlate PD-ECGF expression with tumour vascularization, prognosis, and response to chemotherapy.

A methodology for effective implementation of lean strategies and its performance evaluation in manufacturing organizations

Purpose – The purpose of this paper is to develop an effective methodology for implementing lean manufacturing strategies and a leanness evaluation metric using continuous performance measurement (CPM). Design/methodology/approach – Based on five lean principles, a systematic lean implementation methodology for manufacturing organizations has been proposed. A simplified leanness evaluation metric consisting of both efficiency and effectiveness attributes of manufacturing performance has been developed for continuous evaluation of lean implementation. A case study to validate the proposed methodology has been conducted and proposed CPM metric has been used to assess the manufacturing leanness. Findings – Proposed methodology is able to systematically identify manufacturing wastes, select appropriate lean tools, identify relevant performance indicators, achieve significant performance improvement and establish lean culture in the organization. Continuous performance measurement matrices in terms of efficiency and effectiveness are proved to be appropriate methods for continuous evaluation of lean performance. Research limitations/implications – Effectiveness of the method developed has been demonstrated by applying it in a real life assembly process. However, more tests/applications will be necessary to generalize the findings. Practical implications – Results show that applying the methods developed, managers can successfully identify and remove manufacturing wastes from their production processes. By improving process efficiency, they can optimize their resource allocations. Manufacturers now have a validated step by step methodology for successfully implementing lean strategies. Originality/value – According to the authors’ best knowledge, this is the first known study that proposed a systematic lean implementation methodology based on lean principles and continuous improvement techniques. Evaluation of performance improvement by lean strategies is a critical issue. This study develops a simplified leanness evaluation metric considering both efficiency and effectiveness attributes and integrates it with the lean implementation methodology.

Fibrogenic stresses activate different mitogen-activated protein kinase pathways in renal epithelial, endothelial or fibroblast cell populations

Fibrogenic stresses promote progression of renal tubulointerstitial fibrosis, disparately affecting survival, proliferation and trans-differentiation of intrinsic renal cell populations through ill-defined biomolecular pathways. We investigated the effect of fibrogenic stresses on the activation of cell-specific mitogen-activated protein kinase (MAPK) in renal fibroblast, epithelial and endothelial cell populations. The relative outcomes (cell death, proliferation, trans-differentiation) associated with activation or inhibition of extracellular-regulated protein kinase (ERK) or stress activated/c-Jun N terminal kinase (JNK) were analysed in each renal cell population after challenge with oxidative stress (1 mmol/L H2O2), transforming growth factor-beta1 (TGF-beta1, 10 ng/mL) or tumour necrosis factor-alpha (TNF-alpha, 50 ng/mL) over 0-20 h. Apoptosis increased significantly in all cell types after oxidative stress (P < 0.05). In fibroblasts, oxidative stress caused the activation of ERK (pERK) but not JNK (pJNK). Inhibition of ERK by PD98059 supported its role in a fibroblast death pathway. In epithelial and endothelial cells, oxidative stress-induced apoptosis was preceded by early induction of pERK, but its inhibition did not support a pro-apoptotic role. Early ERK activity may be conducive to their survival or promote the trans-differentiation of epithelial cells. In epithelial and endothelial cells, oxidative stress induced pJNK acutely. Pretreatment with SP600125 (JNK inhibitor) verified its pro-apoptotic activity only in epithelial cells. Transforming growth factor-beta1 did not significantly alter mitosis or apoptosis in any of the cell types, nor did it alter MAPK activity. Tumor necrosis factor-alpha caused increased apoptosis with no associated change in MAPK activity. Our results demonstrate renal cell-specific differences in the activation of ERK and JNK following fibrotic insult, which may be useful for targeting excessive fibroblast proliferation in chronic fibrosis.

Exploring pedestrian accessibility and walkability : insight from public place observations in inner-urban higher density Brisbane, Australia

As planners work to create more sustainable and liveable urban environments, a priority is to transition away from prioritising the automobile and towards enhancing the pedestrian experience. Thus, this research explores the experience of pedestrian accessibility in inner-urban higher-density Brisbane in Australia, drawing on findings from semi-structured in-depth interviews with 24 residents and over 100 hours of public place observations in three case-study neighbourhoods. The interviews took place in residents homes and explored their experience of higher density living and their neighbourhood, whilst observations were recorded through a combination of methods including photographs, sketch maps, recordings and field journals. Observation locations included retail and commercial space, roads, parkland and open space, with multiple observations at each location. A thematic analysis identified common themes in both interviews and the observations, with this paper focusing on residents’ lived experience in urban built environments. This analysis revealed that pedestrian accessibility is linked to access to local amenities and direct routes, aesthetics, sense of community, ownership of space and safety. In particular, observations revealed how pedestrian accessibility and route-taking works with, against or in spite of the design features of urban environments, as well as the importance of the social use of the built environment. Residents spoke about although walking quick and preferred for local amenities, the decision to walk was moderated by factors such as time of day and perceived safety. Measures to ensure and improve the pedestrian accessibility of urban areas needs to take into account the propensity for people to prefer and improvise direct routes (often to the detriment of traffic safety considerations), the importance of ongoing maintenance and upgrading of walking infrastructure and the importance of aesthetically pleasing and safe walking environments. By combining interviews and observations, this research highlights the current dominance of the automobile culture in Brisbane and the layers of meaning, experiences and complexity hidden within the pedestrian experience.

Ananyi (Going) by Tjupi Band

Research background: Ananyi (Going) is an intercultural music project with lyrics sung in Luritja and English, undertaken in collaboration with the Tjupi Band and producer Jeffrey McLaughlin. The project contributes to cultural maintenance for Australian First Nations peoples, and is informed by prior work in this area by scholars including Peter Dunbar-Hall, Chris Gibson and Karl Neuenfeldt. These existing studies have discussed the complexities of intercultural collaboration, and the types of cultural politics that are involved when Indigenous and non-Indigenous musicians and scholars work together on projects of cultural significance. Critical race theory has also informed the creative work, as a means of interpreting the implicit and explicit discourses of race that arise through intercultural creative practice. The project asked the research question, how can collaborative music making contribute to intercultural understanding and the maintenance of Australian First Nations languages and cultures? Research contribution: The project has identified that recorded popular music is important in the maintenance of Luritja language and culture, and that intercultural collaboration in the areas of digital sound production and distribution can assist with cultural maintenance in both local and national contexts. Research significance: The compact disc was released on the CAAMA Music label, and supported through competitive grants from the Australian Government’s Contemporary Music Touring Grant and the Arnhem Land Progress Association (ALPA). The research context of the work is detailed in Brydie-Leigh Bartleet and Gavin Carfoot 2013. "Desert harmony: Stories of collaboration between Indigenous musicians and university students." International Education Journal: Comparative Perspectives 12 (1): 180-196.

Desert harmony : stories of collaboration between Indigenous musicians and university students

This article will discuss the ways in which community service learning programs in music can foster meaningful collaborations between universities and Indigenous communities. Drawing on recent pedagogical literature on service learning and insights from a four-year partnership between Australian Indigenous musicians at the Winanjjikari Music Centre in Tennant Creek and music students from Queensland Conservatorium Griffith University, it will describe how such programs can facilitate significant cross-cultural exchanges between students and Indigenous communities. By drawing on observations and interview data from those involved in the project, this paper argues that these partnerships can both assist communities with activities such as cultural maintenance, and provide students with intercultural experiences that have the potential to transform their understandings of Indigenous culture.

Circle Stories

Research background: Circle Stories was a live performance curated by Brydie-Leigh Bartleet, Naomi Sunderland, Gavin Carfoot and the Winanjjikari Music Centre as part of the Desert Harmony Festival 2013. The performance was the culmination of five years of research into intercultural performing arts practice, undertaken in partnership with Barkly Regional Arts. This work has built on existing scholarly work in community service learning by Marilynne Boyle-Baise, approaches to intercultural music making with Australian First Peoples by Karl Neuenfeldt, and studies of Indigenous popular music by Peter Dunbar-Hall and Chris Gibson. The performance followed the popular songwriters’ circle approach, in which Aboriginal musicians and elders presented their songs along with tertiary music students, as part of a broader dialogue with each other and the audience. Each performance provided an opportunity to highlight the importance of music in the development of intercultural knowledge and understanding. The project asked the research question, how can collaborative music performance foster mutual learning, intercultural knowledge and reconciliation? Research contribution: The project development and performance of Circle Stories identified that mutual learning and intercultural knowledge can result most effectively through long-term and meaningful relationships underpinning collaborative creative practice. Research significance: Following a general call for proposals, the performance was peer reviewed and selected for inclusion in the Desert Harmony Festival program. The research context of the work is detailed in Brydie-Leigh Bartleet and Gavin Carfoot 2013. "Desert harmony: Stories of collaboration between Indigenous musicians and university students." International Education Journal: Comparative Perspectives 12 (1): 180-196.

Partial mediation role of self-efficacy between positive social interaction and mental health in family caregivers for dementia patients in Shanghai

We explored the mediation effect of caregiver self-efficacy on the influences of behavioral and psychological symptoms (BPSD) of dementia care recipients (CRs) or family caregivers’ (CGs) social supports (informational, tangible and affectionate support and positive social interaction) on CGs’ mental health. We interviewed 196 CGs, using a battery of measures including demographic data of the dyads, CRs’ dementia-related impairments, and CGs’ social support, self-efficacy and the Medical Outcome Study (MOS) Short-Form (SF-36) Health Survey. Multiple regression analyses showed that gathering information on self-efficacy and managing CG distress self-efficacy were the partial mediators of the relationship between positive social interaction and CG mental health. Managing caregiving distress self-efficacy also partial mediated the impact of BPSD on CG mental health. We discuss implications of the results for improving mental health of the target population in mainland China.

Understanding the abnormal brain activity in epilepsy as a potential predictor of the onset of an epileptic seizure

The Brain Research Institute (BRI) uses various types of indirect measurements, including EEG and fMRI, to understand and assess brain activity and function. As well as the recovery of generic information about brain function, research also focuses on the utilisation of such data and understanding to study the initiation, dynamics, spread and suppression of epileptic seizures. To assist with the future focussing of this aspect of their research, the BRI asked the MISG 2010 participants to examine how the available EEG and fMRI data and current knowledge about epilepsy should be analysed and interpreted to yield an enhanced understanding about brain activity occurring before, at commencement of, during, and after a seizure. Though the deliberations of the study group were wide ranging in terms of the related matters considered and discussed, considerable progress was made with the following three aspects. (1) The science behind brain activity investigations depends crucially on the quality of the analysis and interpretation of, as well as the recovery of information from, EEG and fMRI measurements. A number of specific methodologies were discussed and formalised, including independent component analysis, principal component analysis, profile monitoring and change point analysis (hidden Markov modelling, time series analysis, discontinuity identification). (2) Even though EEG measurements accurately and very sensitively record the onset of an epileptic event or seizure, they are, from the perspective of understanding the internal initiation and localisation, of limited utility. They only record neuronal activity in the cortical (surface layer) neurons of the brain, which is a direct reflection of the type of electrical activity they have been designed to record. 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Conversion of neutral C2COC2 to C4CO. potential interstellar molecules

Both [C4CO]−· and [C2COC2]−· are formed in the ion source of a VG ZAB 2HF mass spectrometer by the respective processes HO− + Me3Si–CC–CC–CO–CMe3 → [C4CO]−· + Me3SiOH + Me3C·, and Me3Si–CC–CO–CC–SiMe3 + SF6 + e → [C2COC2]−· + 2Me3SiF + SF4. The second synthetic pathway involves a double desilylation reaction similar to that first reported by Squires. The two radical anion isomers produce different and characteristic charge reversal spectra upon collisional activation. In contrast, following collision induced charge stripping, both radical anions produce neutral C4CO as evidenced by the identical neutralisation reionisation (−NR+) spectra. The exclusive rearrangement of C213COC2 to C413CO indicates that 12C–O bond formation is not involved in the reaction. Ab initio calculations (at the RCCSD(T)/aug-cc-pVDZ//B3LYP/6-31G∗ level of theory) have been used to investigate the reaction coordinates on the potential surfaces for both singlet and triplet rearrangements of neutral C2COC2. Singlet C2COC2 is less stable than singlet C4CO by 78.8 kcal mol−1 and requires only 8.5 kcal mol−1 of additional energy to effect conversion to C4CO by a rearrangement sequence involving three C–C ring opening/cyclisation steps.

Expanding Emergency Department capacity : a multisite study

Objectives: To i) identify predictors of admission, and ii) describe outcomes for patients who arrived via ambulance to three Australian public Emergency Departments (EDs), before and after the opening of 41 additional ED beds within the area. Methods: A retrospective, comparative, cohort study using deterministically linked health data collected between 3 September 2006 and 2 September 2008. Data included ambulance offload delay, time to see doctor, ED length of stay (ED LOS), admission requirement, access block, hospital length of stay and in-hospital mortality. Logistic regression analysis was undertaken to identify predictors of hospital admission. Results: One third of all 286,037 ED presentations were via ambulance (n= 79,196) and 40.3% required admission. After increasing emergency capacity, the only outcome measure to improve was in-hospital mortality. Ambulance offload delay, time to see doctor, ED length of stay (ED LOS), admission requirement, access block, hospital length of stay did not improve. Strong predictors of admission before and after increased capacity included: age over 65 years, Australian Triage Scale (ATS) category 1-3, diagnoses of circulatory or respiratory conditions and ED LOS > 4 hours. With additional capacity the odds ratios for these predictors increased for age >65 and ED LOS > 4 hours and decreased for triage category and ED diagnoses. Conclusions: Expanding ED capacity from 81 to 122 beds within a health service area impacted favourably on mortality outcomes but not on time-related service outcomes such as ambulance offload time, time to see doctor and ED LOS. To improve all service outcomes, when altering (increasing/decreasing) ED bed numbers, the whole healthcare system needs to be considered.

Prostate radiotherapy treatment plan quality : effects of hip prostheses

Introduction This study aimed to examine the geometric and dosimetric results when radiotherapy treatment plans are designed for prostate cancer patients with hip prostheses. Methods Ten EBRT treatment plans for localised prostate cancer, in the presence of hip prostheses, were analysed and compared with a reference set of 196 treatment plans for localised prostate cancer in patients without prostheses. Crowe et al.’s TADA code [1] was used to extract treatment plan parameters and evaluate doses to target volumes and critical structures against recommended goals [2] and constraints [3, 4]. Results The need to avoid transmitting the radiation beam through the hip prostheses limited the range of gantry angles available for use in both the rotational (VMAT) and the non-rotational (3DCRT and IMRT) radiotherapy treatments. This geometric limitation (exemplified in the VMAT data shown in Fig. 1) reduced the overall quality of the treatment plans for patients with prostheses compared to the reference plans. All plans with prostheses failed the PTV dose homogeneity requirement [2], whereas only 4 % of the plans without prostheses failed this test. Several treatment plans for patients with hip prostheses also failed the QUANTEC requirements that less than 50 % of the rectum receive 50 Gy and less than 35 % of the rectum receive 60 Gy to keep the grade 3 toxicity rate below 10 % [3], or the Hansen and Roach requirement that less than 25 % of the bladder receive 75 Gy [4]. Discussion and conclusions The results of this study exemplify the difficulty of designing prostate radiotherapy treatment plans, where beams provide adequate doses to targeted tissues while avoiding nearby organs at risk, when the presence of hip prostheses limits the available treatment geometries. This work provides qualitative evidence of the compromised dose distributions that can result, in such cases.