Principal component and linkage analysis of cardiovascular risk traits in the Norfolk isolate

OBJECTIVE(S): An individual's risk of developing cardiovascular disease (CVD) is influenced by genetic factors. This study focussed on mapping genetic loci for CVD-risk traits in a unique population isolate derived from Norfolk Island. METHODS: This investigation focussed on 377 individuals descended from the population founders. Principal component analysis was used to extract orthogonal components from 11 cardiovascular risk traits. Multipoint variance component methods were used to assess genome-wide linkage using SOLAR to the derived factors. A total of 285 of the 377 related individuals were informative for linkage analysis. RESULTS: A total of 4 principal components accounting for 83% of the total variance were derived. Principal component 1 was loaded with body size indicators; principal component 2 with body size, cholesterol and triglyceride levels; principal component 3 with the blood pressures; and principal component 4 with LDL-cholesterol and total cholesterol levels. Suggestive evidence of linkage for principal component 2 (h(2) = 0.35) was observed on chromosome 5q35 (LOD = 1.85; p = 0.0008). While peak regions on chromosome 10p11.2 (LOD = 1.27; p = 0.005) and 12q13 (LOD = 1.63; p = 0.003) were observed to segregate with principal components 1 (h(2) = 0.33) and 4 (h(2) = 0.42), respectively. CONCLUSION(S): This study investigated a number of CVD risk traits in a unique isolated population. Findings support the clustering of CVD risk traits and provide interesting evidence of a region on chromosome 5q35 segregating with weight, waist circumference, HDL-c and total triglyceride levels.

“Would you; could you; on a boat?” Wait-time and travel-time activities during river ferry journeys and their relationship to overall satisfaction in Brisbane Queensland

This study investigates travel behaviour and wait-time activities as a component of passenger satisfaction with public transport in Brisbane, Australia. Australian transport planners recognise a variety of benefits to encouraging a mode shift away from automobile travel in favour of active and public transport use. Efforts to increase public transport ridership have included introducing state of the art passenger information systems, improving physical station access, and integrating system pricing, routes and scheduling for train, bus and ferry. Previous research regarding satisfaction with public transport emphasizes technical dimensions of service quality, including the timing and reliability of service. Those factors might be especially significant for frequent (commuting) travellers who look to balance the cost and efficiency of their travel options. In contrast, infrequent (leisure) passengers may be more concerned with way finding and the sensory experience of the journey. Perhaps due to the small relative proportion of trips made by river ferry compared to bus and rail, this mode of public transport has not received as much attention in travel-behaviour research. This case study of Brisbane’s river ferry system examines ferry passengers at selected terminals during peak and off-peak travel times to find out how travel behaviours and activities correlate to satisfaction with ferry travel. Data include 416 questionnaires completed by passengers intercepted during wait times at seven CityCat terminals in Brisbane. Descriptive statistical analysis revealed associations between specific wait time activities and satisfaction levels that could inform planners seeking to increase ridership and quality of life through ferry-oriented development.

Genome-wide association study identifies a possible susceptibility locus for endometrial cancer

Background: Genome-wide association studies (GWAS) have identified more than 100 genetic loci for various cancers. However, only one is for endometrial cancer. Methods: We conducted a three-stage GWAS including 8,492 endometrial cancer cases and 16,596 controls. After analyzing 585,963 single-nucleotide polymorphisms (SNP) in 832 cases and 2,682 controls (stage I) from the Shanghai Endometrial Cancer Genetics Study, we selected the top 106 SNPs for in silico replication among 1,265 cases and 5,190 controls from the Australian/British Endometrial Cancer GWAS (stage II). Nine SNPs showed results consistent in direction with stage I with P < 0.1. These nine SNPs were investigated among 459 cases and 558 controls (stage IIIa) and six SNPs showed a direction of association consistent with stages I and II. These six SNPs, plus two additional SNPs selected on the basis of linkage disequilibrium and P values in stage II, were investigated among 5,936 cases and 8,166 controls from an additional 11 studies (stage IIIb). Results: SNP rs1202524, near the CAPN9 gene on chromosome 1q42.2, showed a consistent association with endometrial cancer risk across all three stages, with ORs of 1.09 [95% confidence interval (CI), 1.03–1.16] for the A/G genotype and 1.17 (95% CI, 1.05–1.30) for the G/G genotype (P = 1.6 × 10−4 in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% CI) of 1.11 (1.04–1.18) and 1.21 (1.08–1.35), respectively (P = 2.4 × 10−5). Conclusions: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. Impact: This study identified a potential genetic locus for endometrial cancer risk

The effect of varied test instructions on neuropsychological performance following mild traumatic brain injury : an investigation of ‘diagnosis threat’

Diagnosis threat is a psychosocial factor that has been proposed to contribute to poor outcomes following mild traumatic brain injury (mTBI). This threat is thought to impair the cognitive test performance of individuals with mTBI because of negative injury stereotypes. University students (N= 45, 62.2% female) with a history of mTBI were randomly allocated to a diagnosis threat (DT, n=15), reduced threat (DT-reduced, n=15) or neutral (n=15) group. The reduced threat condition invoked a positive stereotype (i.e., that people with mTBI can perform well on cognitive tests). All participants were given neutral instructions before they completed baseline tests of: a) objective cognitive function across a number of domains; b) psychological symptoms; and, c) PCS symptoms, including self-reported cognitive and emotional difficulties. Participants then received either neutral, DT or DT-reduced instructions, before repeating the tests. Results were analyzed using separate mixed model ANOVAs; one for each dependent measure. The only significant result was for the 2 X 3 ANOVA on an objective test of attention/working memory, Digit Span, p<.05, such that the DT-reduced group performed better than the other groups, which were not different from each other. Although not consistent with predictions or earlier DT studies, the absence of group differences on most tests fits with several recent DT findings. The results of this study suggest that it is timely to reconsider the role of DT as a unique contributor to poor mTBI outcome.

Literacy, place-based pedagogies and social justice

Our long-term program of research has considered the relationships between teachers’ work and identities, literacy pedagogies and schooling, particularly in high-poverty communities. Over the past decade, we have worked with teachers to consciously explore with them the possible productive synergies between critical literacy and place-based pedagogies, and the affordances of multimodal and digital literacies for students’ engagement with the places where they live and learn. These studies have been undertaken with teachers working and living in various locales—from the urban fringe to inner suburban areas undergoing urban renewal, to rural and regional communities where poverty and the politics of place bring certain distinctive opportunities and constraints to bear on pedagogy for social justice. There is now wider recognition that “social justice” may need rethinking to foreground the nonhuman world and the relation between people and politics of places, people, and environments in terms of “eco-social justice” (Green 2010; Gruenewald 2003b) or spatial justice (Soja 2011). In this chapter, we explore place as a site of knowing and as an object of study as developed through the Special Forever project by teachers in schools located in the Murray-Darling Basin bioregion. Putting the environment at the center of the literacy curriculum inevitably draws teachers into the politics of place and raises questions concerning what is worth preserving and what should be transformed. We consider how the politics of place both constrains and opens up possibilities for pedagogy for eco-social justice and review the pedagogical work that one teacher, Hannah, undertook with her upper primary class.

Development and validation of anthropometric prediction equations for estimation of lean body mass and appendicular lean soft tissue in Indian men and women

Lean body mass (LBM) and muscle mass remains difficult to quantify in large epidemiological studies due to non-availability of inexpensive methods. We therefore developed anthropometric prediction equations to estimate the LBM and appendicular lean soft tissue (ALST) using dual energy X-ray absorptiometry (DXA) as a reference method. Healthy volunteers (n= 2220; 36% females; age 18-79 y) representing a wide range of body mass index (14-44 kg/m2) participated in this study. Their LBM including ALST was assessed by DXA along with anthropometric measurements. The sample was divided into prediction (60%) and validation (40%) sets. In the prediction set, a number of prediction models were constructed using DXA measured LBM and ALST estimates as dependent variables and a combination of anthropometric indices as independent variables. These equations were cross-validated in the validation set. Simple equations using age, height and weight explained > 90% variation in the LBM and ALST in both men and women. Additional variables (hip and limb circumferences and sum of SFTs) increased the explained variation by 5-8% in the fully adjusted models predicting LBM and ALST. More complex equations using all the above anthropometric variables could predict the DXA measured LBM and ALST accurately as indicated by low standard error of the estimate (LBM: 1.47 kg and 1.63 kg for men and women, respectively) as well as good agreement by Bland Altman analyses. These equations could be a valuable tool in large epidemiological studies assessing these body compartments in Indians and other population groups with similar body composition.

Vision in water

The purpose of this study is to determine visual performance in water, including the influence of pupil size. The water en-vironment was simulated by placing a goggle filled with saline in front of eyes, with apertures placed at the front of the goggle. Correction factors were determined for the different magnification under this condition in order to to estimate vision in water. Experiments were conducted on letter visual acuity (7 participants), grating resolution (8 participants), and grating contrast sensitivity (1 participant). For letter acuity, mean loss in vision in water, compared to corrected vision in air, varied between 1.1 log minutes of arc resolution (logMAR) for a 1mm aperture to 2.2 logMAR for a 7mm aperture. The vision in minutes of arc was described well by a linear relationship with pupil size. For grating acuity, mean loss varied between 1.1 logMAR for a 2mm aperture to 1.2 logMAR for a 6mm aperture. Contrast sensitivity for a 2mm aperture dete-riorated as spatial frequency increased, with 2 log unit loss by 3 cycles/degree. Superimposed on this deterioration were depressions (notches) in sensitivity, with the first three notches occurring at 0.45, 0.8 and 1.3 cycles/degree with esti-mates for water of 0.39, 0.70 and 1.13 cycles/degree. In conclusion, vision in water is poor. It becomes worse as pupil size increases, but the effects are much more marked for letter targets than for grating targets.

Rebuilding in Ranongga : reflecting on practice based research

Two hundred million people are displaced annually due to natural disasters with a further one billion living in inadequate conditions in urban areas. Architects have a responsibility to respond to this statistic as the effects of natural and social disasters become more visibly catastrophic when paired with population rise. The research discussed in this paper initially questions and considers how digital tools can be employed to enhance rebuilding processes, but still achieve sensitive, culturally appropriate and accepted built solutions. Secondly the paper reflects on the impact ‘real-world’ projects have on architectural education. Research aspirations encouraged an atypical ‘research by design’ methodology involving a focused case study in the recently devastated village Keigold, Ranongga, Solomon Islands. Through this qualitative approach specific place data and the accounts of those affected were documented through naturalistic and archival methods of observation and participation. Findings reveal a number of unanticipated results which would have been otherwise undetected if field research within the design and rebuilding process was not undertaken, reflecting the importance of place specific research in the design process. Ultimately, the study proves that it is critical for issues of disaster to be addressed on a local rather than global scale; decisions cannot be speculative, or solved at a distance, but require intensive collaborative work with communities to achieve optimum solutions. Architectural education and design studios would continue to benefit from focused community engagement and field research within the design process.

People living in hilly residential areas in metropolitan Perth have less diabetes : spurious association or important environmental determinant?

BACKGROUND: Variations in 'slope' (how steep or flat the ground is) may be good for health. As walking up hills is a physiologically vigorous physical activity and can contribute to weight control, greater neighbourhood slopes may provide a protective barrier to weight gain, and help prevent Type 2 diabetes onset. We explored whether living in 'hilly' neighbourhoods was associated with diabetes prevalence among the Australian adult population. METHODS: Participants ([greater than or equal to]25years; n=11,406) who completed the Western Australian Health and Wellbeing Surveillance System Survey (2003-2009) were asked whether or not they had medically-diagnosed diabetes. Geographic Information Systems (GIS) software was used to calculate a neighbourhood mean slope score, and other built environment measures at 1600m around each participant's home. Logistic regression models were used to predict the odds of self-reported diabetes after progressive adjustment for individual measures (i.e., age, sex), socioeconomic status (i.e., education, income), built environment, destinations, nutrition, and amount of walking. RESULTS: After full adjustment, the odds of self-reported diabetes was 0.72 (95% CI 0.55-0.95) and 0.52 (95% CI 0.39-0.69) for adults living in neighbourhoods with moderate and higher levels of slope, respectively, compared with adults living in neighbourhoods with the lowest levels of slope. The odds of having diabetes was 13% lower (odds ratio 0.87; 95% CI 0.80-0.94) for each increase of one percent in mean slope. CONCLUSIONS: Living in a hilly neighbourhood may be protective of diabetes onset or this finding is spurious. Nevertheless, the results are promising and have implications for future research and the practice of flattening land in new housing developments.

The association of early life supplemental nutrition with lean body mass and grip strength in adulthood : evidence from APCAPS

In the present study, we examined the associations of early nutrition with adult lean body mass (LBM) and muscle strength in a birth cohort that was established to assess the long-term impact of a nutrition program. Participants (n = 1,446, 32% female) were born near Hyderabad, India, in 29 villages from 1987 to 1990, during which time only intervention villages (n = 15) had a government program that offered balanced protein-calorie supplementation to pregnant women and children. Participants’ LBM and appendicular skeletal muscle mass were measured using dual energy x-ray absorptiometry; grip strength and information on lifestyle indicators, including diet and physical activity level, were also obtained. Ages (mean = 20.3 years) and body mass indexes (weight (kg)/height (m)2; mean = 19.5) of participants in 2 groups were similar. Current dietary energy intake was higher in the intervention group. Unadjusted LBM and grip strength were similar in 2 groups. After adjustment for potential confounders, the intervention group had lower LBM (β = −0.75; P = 0.03), appendicular skeletal muscle mass, and grip strength than did controls, but these differences were small in magnitude (<0.1 standard deviation). Multivariable regression analyses showed that current socioeconomic position, energy intake, and physical activity level had a positive association with adult LBM and muscle strength. This study could not detect a “programming” effect of early nutrition supplementation on adult LBM and muscle strength.

A recurrent network in the lateral amygdala : a mechanism for coincidence detection

Synaptic changes at sensory inputs to the dorsal nucleus of the lateral amygdala (LAd) play a key role in the acquisition and storage of associative fear memory. However, neither the temporal nor spatial architecture of the LAd network response to sensory signals is understood. We developed a method for the elucidation of network behavior. Using this approach, temporally patterned polysynaptic recurrent network responses were found in LAd (intra-LA), both in vitro and in vivo, in response to activation of thalamic sensory afferents. Potentiation of thalamic afferents resulted in a depression of intra-LA synaptic activity, indicating a homeostatic response to changes in synaptic strength within the LAd network. Additionally, the latencies of thalamic afferent triggered recurrent network activity within the LAd overlap with known later occurring cortical afferent latencies. Thus, this recurrent network may facilitate temporal coincidence of sensory afferents within LAd during associative learning.

The Australian Nonprofit Sector Legal and Accounting Almanac 2013

INTRODUCTION CASES For a number of years, Professor Myles McGregor-Lowndes, Frances Hannah and Anne Overell have compiled one to two page summaries of cases involving nonprofit organisations and published them on The Australian Centre for Philanthropy and Nonprofit Studies, Developing Your Organisation (DYO) website.1 You can be alerted of new case summaries as they are posted to the DYO website by subscribing to the ACPNS RSS feed or the ACPNS twitter service.2 There were some very significant cases during 2013, such as Commissioner of Taxation v Cancer & Bowel Research Association (see case notes 2.8.2 and 2.8.11), The Hunger Project case which is under appeal, but could change the face of PBI jurisprudence (see case note 2.8.7) while Home Health Pty Ltd retained the PBI status quo but might have been different if appealed (see case note 2.8.8). For sheer interest there is nothing better in my 30 odd years of reading tax and charity judgements than case involving The Study and Prevention of Psychological Diseases Foundation Incorporated (see case note 2.1.1). It even rivals some of the more bizarre cases from the US jurisdiction of which St Joseph Abbey v Castille (case note 2.10.9) is certainly ‘dead centre’. A set of cases which stand out for attention are those involving New Zealand’s Christchurch Cathedral which anyone with responsibility for heritage-listed buildings should study carefully, for implications in relation to their own circumstances. A number of cases summarised in this Almanac are working their way through the appeals process and care should be taken with their application. In addition, some of the cases are from jurisdictions outside Australia, and readers should exercise caution when considering the implications of these cases for Australian law. LEGISLATION The Almanac includes a review of major statutory amendments during 2013, which are relevant to the nonprofit sector in all Australian jurisdictions. Special thanks must go to Nathan MacDonald and the JusticeConnect team for providing legislative updates for Victoria. SPECIAL ISSUES DURING 2013 A number of legal practitioners have contributed articles on significant legal issues facing nonprofit organisations: charitable trusts giving to government entities (Alice Macdougall); workplace bullying (Tim Longwill); and privacy (James Tan and Nina Brewer). WORLD ROUND-UP Major developments from the UK and Ireland (Kerry O’Halloran), Canada (Peter Broder), New Zealand (Michael Gousmett and Susan Barker) and Jamaica (Frances Hannah) are all summarised in a review of a significant part of the common law charity jurisdictions. WHAT DOES 2014 HOLD The final section moves from looking in the rear view mirror to peering out the front windscreen to discern the reform agenda. The view from the windscreen in 2013 was of considerable reform traffic at the Commonwealth level jostling for a place in the parliamentary agenda. This year is quite different with a smaller number of vehicles ahead, but the potential for significant impact.

‘Click’ functionalised polymer resins : a new approach to the synthesis of surface attached bipyridinium and naphthalene diimide [2]rotaxanes

Herein we describe the design and synthesis of a series of solid-tethered [2]rotaxanes utilising crown ether-naphthalene diimide or crown ether- bipyridinium host guest interactions. TentaGel polystyrene resins were initially modified in a two-stage procedure to azide functionalised beads before the target supramolecular architectures were attached using a copper catalysed “click” procedure. The final assembly was examined using IR spectroscopy and gel-phase 1H High Resolution Magic Angle Spinning (HR MAS) NMR spectroscopy. The HR MAS technique enabled a direct comparison between the solid-tethered architectures and the synthesis and characterisation of analogous solution-based [2]rotaxanes to be made.

New approaches to the synthesis of strapped porphyrin containing bipyridinium [2]rotaxanes

Inspired by the interesting photo- and electrochemical properties observed in bipyridinium and porphyrin containing interlocked catenanes, herein we describe new approaches towards the synthesis of related rotaxanes. Previous efforts in this domain had been hampered by the limited range of chemical reactions that are compatible with these motifs, however the use of a “click” methodology, together with a better understanding of the size of these strapped porphyrin macrocycles, resulted in the synthesis of a bipyridinium porphyrin [2]rotaxane in modest yields. X-ray crystallography of the zinc metalloporphyrin macrocycle used in this study revealed that in the solid state, these strapped porphyrins adopt a 1-dimensional coordination polymer, in which an oxygen atom in the strap of one macrocycle is coordinated to the zinc metal center in an adjacent porphyrin ring

A variant of the breast cancer type 2 susceptibility protein (BRC) repeat is essential for the RECQL5 Helicase to interact with RAD51 Recombinase for genome stabilization

The BRC repeat is a structural motif in the tumor suppressor BRCA2 (breast cancer type 2 susceptibility protein), which promotes homologous recombination (HR) by regulating RAD51 recombinase activity. To date, the BRC repeat has not been observed in other proteins, so that its role in HR is inferred only in the context of BRCA2. Here, we identified a BRC repeat variant, named BRCv, in the RECQL5 helicase, which possesses anti-recombinase activity in vitro and suppresses HR and promotes cellular resistance to camptothecin-induced replication stress in vivo. RECQL5-BRCv interacted with RAD51 through two conserved motifs similar to those in the BRCA2-BRC repeat. Mutations of either motif compromised functions of RECQL5, including association with RAD51, inhibition of RAD51-mediated D-loop formation, suppression of sister chromatid exchange, and resistance to camptothecin-induced replication stress. Potential BRCvs were also found in other HR regulatory proteins, including Srs2 and Sgs1, which possess anti-recombinase activities similar to that of RECQL5. A point mutation in the predicted Srs2-BRCv disrupted the ability of the protein to bind RAD51 and to inhibit D-loop formation. Thus, BRC is a common RAD51 interaction module that can be utilized by different proteins to either promote HR, as in the case of BRCA2, or to suppress HR, as in RECQL5.