Association of heparan sulfate proteoglycans SDC1 and SDC4 polymorphisms with breast cancer in an Australian Caucasian population

Breast cancer is a common disease in both developing and developed countries with early identification and treatment improving prognosis and survival. Heparan sulfate proteoglycans (HSPGs) are key components of the extracellular matrix (ECM) that mediate cell adhesion, motility, proliferation, invasion and cell signalling. Members of the syndecan family of HSPGs have been identified to be involved in breast cancer progression through their varied interactions with a number of growth factors, ligands and receptors. Specifically, high expression levels of syndecan-1 (SDC1) have been demonstrated in more invasive breast tumours while elevated syndecan-4 (SDC4) levels have been identified to correspond with improved prognosis. With genetic changes in the syndecans and their association with breast cancers plausible, we examined two single nucleotide polymorphisms in SDC1 (rs1131351) and SDC4 (rs67068737) within an Australian Caucasian breast cancer case/control population. No association was found with SDC4 and breast cancer in our population. However, a significant association between SDC1 and breast cancer was identified in both our case/control population and in a replication cohort. When both populations were combined for analysis, this association became more significant (genotype, p = 0.0003; allele, p = 0.0001). This data suggests an increased risk of developing breast cancer associated with the presence of the C allele of the SDC1 rs1131351 single nucleotide polymorphism (SNP) and may provide a marker toward early breast cancer detection.

Wide-band spectral power fluctuations characterize the response of simulated cortical networks to increasing stimulus intensity

The hippocampus is an anatomically distinct region of the medial temporal lobe that plays a critical role in the formation of declarative memories. Here we show that a computer simulation of simple compartmental cells organized with basic hippocampal connectivity is capable of producing stimulus intensity sensitive wide-band fluctuations of spectral power similar to that seen in real EEG. While previous computational models have been designed to assess the viability of the putative mechanisms of memory storage and retrieval, they have generally been too abstract to allow comparison with empirical data. Furthermore, while the anatomical connectivity and organization of the hippocampus is well defined, many questions regarding the mechanisms that mediate large-scale synaptic integration remain unanswered. For this reason we focus less on the specifics of changing synaptic weights and more on the population dynamics. Spectral power in four distinct frequency bands were derived from simulated field potentials of the computational model and found to depend on the intensity of a random input. The majority of power occurred in the lowest frequency band (3-6 Hz) and was greatest to the lowest intensity stimulus condition (1% maximal stimulus). In contrast, higher frequency bands ranging from 7-45 Hz show an increase in power directly related with an increase in stimulus intensity. This trend continues up to a stimulus level of 15% to 20% of the maximal input, above which power falls dramatically. These results suggest that the relative power of intrinsic network oscillations are dependent upon the level of activation and that above threshold levels all frequencies are damped, perhaps due to over activation of inhibitory interneurons.

Weight and weight change following breast cancer : evidence from a prospective, population-based, breast cancer cohort study

Background: While weight gain following breast cancer is considered common, results supporting these findings are dated. This work describes changes in body weight following breast cancer over 72 months, compares weight with normative data and explores whether weight changes over time are associated with personal, diagnostic, treatment or behavioral characteristics. Methods: A population-based sample of 287 Australian women diagnosed with early-stage invasive breast cancer was assessed prospectively at six, 12, 18 and 72 months post-surgery. Weight was clinically measured and linear mixed models were used to explore associations between weight and participant characteristics (collected via self-administered questionnaire). Those with BMI changes of one or more units were considered to have experienced clinically significant changes in weight. Results: More than half (57%) of participants were overweight or obese at 6 months post-surgery, and by 72 months post-surgery 68% of women were overweight or obese. Among those who gained more weight than age-matched norms, clinically significant weight gain between 6 and 18 months and 6 and 72 months post-surgery was observed in 24% and 39% of participants, respectively (median [range] weight gain: 3.9kg [2.0-11.3kg] and 5.2kg [0.6-28.7], respectively). Clinically-significant weight losses were observed in up to 24% of the sample (median [range] weight loss between 6 and 72 months post-surgery: -6.4kg [-1.9--24.6kg]). More extensive lymph node removal, being treated on the non-dominant side, receiving radiation therapy and lower physical activity levels at 6 months was associated with higher body weights post-breast cancer (group differences >3kg; all p<0.05). Conclusions: While average weight gain among breast cancer survivors in the long-term is small, subgroups of women experience greater gains linked with adverse health and above that experienced by age-matched counterparts. Weight change post-breast cancer is a contemporary public health issue and the integration of healthy weight education and support into standard breast cancer care has potential to significantly improve the length and quality of cancer survivorship.

Is biggest best? A comparative analysis of the financial viability of the Brisbane City Council

Structural reform through forced mergers has been a dominant feature of Australian local government for decades. Advocates of compulsory consolidation contend that larger municipalities perform better across a wide range of attributes, including financial sustainability. While empirical scholars of local government have invested considerable effort into investigating these claims, no-one has yet examined the performance of Brisbane City Council against other local authorities, despite the fact that it is by far the largest council in Australia. This paper seeks to remedy this neglect by comparing Brisbane with Sydney City Council, an average of six south east Queensland councils and an average of ten metropolitan New South Wales councils against four measures of financial performance over the period 2008 to 2011.

Accounting for management costs in sensitivity analyses of matrix population models

Traditional sensitivity and elasticity analyses of matrix population models have been used to inform management decisions, but they ignore the economic costs of manipulating vital rates. For example, the growth rate of a population is often most sensitive to changes in adult survival rate, but this does not mean that increasing that rate is the best option for managing the population because it may be much more expensive than other options. To explore how managers should optimize their manipulation of vital rates, we incorporated the cost of changing those rates into matrix population models. We derived analytic expressions for locations in parameter space where managers should shift between management of fecundity and survival, for the balance between fecundity and survival management at those boundaries, and for the allocation of management resources to sustain that optimal balance. For simple matrices, the optimal budget allocation can often be expressed as simple functions of vital rates and the relative costs of changing them. We applied our method to management of the Helmeted Honeyeater (Lichenostomus melanops cassidix; an endangered Australian bird) and the koala (Phascolarctos cinereus) as examples. Our method showed that cost-efficient management of the Helmeted Honeyeater should focus on increasing fecundity via nest protection, whereas optimal koala management should focus on manipulating both fecundity and survival simultaneously. These findings are contrary to the cost-negligent recommendations of elasticity analysis, which would suggest focusing on managing survival in both cases. A further investigation of Helmeted Honeyeater management options, based on an individual-based model incorporating density dependence, spatial structure, and environmental stochasticity, confirmed that fecundity management was the most cost-effective strategy. Our results demonstrate that decisions that ignore economic factors will reduce management efficiency. ©2006 Society for Conservation Biology.

Extinction risk analysis of exploited green turtle stocks in the Indo-Pacific

In parts of the Indo-Pacific, large-scale exploitation of the green turtle Chelonia mydas continues to pose a serious threat to the persistence of this species; yet very few studies have assessed the pattern and extent of the impact of such harvests. We used demographic and genetic data in an age-based model to investigate the viability of an exploited green turtle stock from Aru, south-east Indonesia. We found that populations are decreasing under current exploitation pressures. The effects of increasingly severe exploitation activities at foraging and nesting habitat varied depending on the migratory patterns of the stock. Our model predicted a rapid decline of the Aru stock in Indonesia under local exploitation pressure and a shift in the genetic composition of the stock. We used the model to investigate the influence of different types of conservation actions on the persistence of the Aru stock. The results show that local management actions such as nest protection and reducing harvests of adult nesting and foraging turtles can have considerable conservation outcomes and result in the long-term persistence of genetically distinct management units. © 2010 The Authors. Animal Conservation © 2010 The Zoological Society of London.

Historical intake and elimination of polychlorinated biphenyls and organochlorine pesticides by the Australian population reconstructed from biomonitoring data

Quantifying the competing rates of intake and elimination of persistent organic pollutants (POPs) in the human body is necessary to understand the levels and trends of POPs at a population level. In this paper we reconstruct the historical intake and elimination of ten polychlorinated biphenyls (PCBs) and five organochlorine pesticides (OCPs) from Australian biomonitoring data by fitting a population-level pharmacokinetic (PK) model. Our analysis exploits two sets of cross-sectional biomonitoring data for PCBs and OCPs in pooled blood serum samples from the Australian population that were collected in 2003 and 2009. The modeled adult reference intakes in 1975 for PCB congeners ranged from 0.89 to 24.5 ng/kg bw/day, lower than the daily intakes of OCPs ranging from 73 to 970 ng/kg bw/day. Modeled intake rates are declining with half-times from 1.1 to 1.3 years for PCB congeners and 0.83 to 0.97 years for OCPs. The shortest modeled intrinsic human elimination half-life among the compounds studied here is 6.4 years for hexachlorobenzene, and the longest is 30 years for PCB-74. Our results indicate that it is feasible to reconstruct intakes and to estimate intrinsic human elimination half-lives using the population-level PK model and biomonitoring data only. Our modeled intrinsic human elimination half-lives are in good agreement with values from a similar study carried out for the population of the United Kingdom, and are generally longer than reported values from other industrialized countries in the Northern Hemisphere.

Assessment of the concentrations of polybrominated diphenyl ether flame retardants in the Australian population : levels in blood

Polybrominated diphenyl ethers (PBDEs), a common class of brominated flame retardants, are a ubiquitous part of our built environment, and for many years have contributed to improved public safety by reducing the flammability of everyday goods. Recently, PBDEs have come under increased international attention because of their potential to impact upon the environment and human health. Some PBDE compounds have been nominated for possible inclusion on the Stockholm Convention on Persistent Organic Pollutants, to which Australia is a Party. Work under the Stockholm Convention has demonstrated the capacity of some PBDEs to persist and accumulate in the environment and to be carried long distances. Much is unknown about the impact of PBDEs on living organisms, however recent studies show that some PBDEs can inhibit growth in colonies of plankton and algae and depress the reproduction of zooplankton. Laboratory mice and rats have also shown liver disturbances and damage to developing nervous systems as a result of exposure to PBDEs. In 2004, the Australian Government Department of the Environment and Water Resources began three studies to examine levels of PBDEs in aquatic sediments, indoor environments and human blood, as knowledge about PBDEs in Australia was very limited. The aim of these studies was to improve this knowledge base so that governments were in a better position to consider appropriate management actions. Due to the high costs for laboratory analysis of PBDEs, the number of samples collected for each study was limited and so caution is required when interpreting the findings. Nevertheless, these studies will provide governments with an indication of how prevalent PBDEs are in the Australian population and the environment and will also contribute to international knowledge about these chemicals. The Department of the Environment and Water Resources will be working closely with othergovernment agencies, industry and the community to investigate any further action that may be required to address PBDEs in Australia.

Organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs) in the Australian population: Levels in human milk

This study arose out of the 2002 Review of the PCB Management Plan by the Scheduled Waste Management Network (SWMN) and the National Advisory Body (NAB). The Review indicated it would be beneficial to obtain some data on the levels of organochlorine pesticides (OCPs) in the Australian population. In 2002, the Environment Protection and Heritage Standing Committee (EPHSC) agreed and noted that the Australian Government Department of the Environment and Heritage (DEH) would commission a study using the same samples from the National Dioxins Program (NDP) breast milk study collected in 2002- 03. The study, however, was also broadened to include polybrominated diphenyl ethers (PBDEs).

A novel population balance model for the dilute acid hydrolysis of hemicellulose

Acid hydrolysis is a popular pretreatment for removing hemicellulose from lignocelluloses in order to produce a digestible substrate for enzymatic saccharification. In this work, a novel model for the dilute acid hydrolysis of hemicellulose within sugarcane bagasse is presented and calibrated against experimental oligomer profiles. The efficacy of mathematical models as hydrolysis yield predictors and as vehicles for investigating the mechanisms of acid hydrolysis is also examined. Experimental xylose, oligomer (degree of polymerisation 2 to 6) and furfural yield profiles were obtained for bagasse under dilute acid hydrolysis conditions at temperatures ranging from 110C to 170C. Population balance kinetics, diffusion and porosity evolution were incorporated into a mathematical model of the acid hydrolysis of sugarcane bagasse. This model was able to produce a good fit to experimental xylose yield data with only three unknown kinetic parameters ka, kb and kd. However, fitting this same model to an expanded data set of oligomeric and furfural yield profiles did not successfully reproduce the experimental results. It was found that a ``hard-to-hydrolyse'' parameter, $\alpha$, was required in the model to ensure reproducibility of the experimental oligomer profiles at 110C, 125C and 140C. The parameters obtained through the fitting exercises at lower temperatures were able to be used to predict the oligomer profiles at 155C and 170C with promising results. The interpretation of kinetic parameters obtained by fitting a model to only a single set of data may be ambiguous. Although these parameters may correctly reproduce the data, they may not be indicative of the actual rate parameters, unless some care has been taken to ensure that the model describes the true mechanisms of acid hydrolysis. It is possible to challenge the robustness of the model by expanding the experimental data set and hence limiting the parameter space for the fitting parameters. The novel combination of ``hard-to-hydrolyse'' and population balance dynamics in the model presented here appears to stand up to such rigorous fitting constraints.

Frequency of convergence and accommodative disorders in a clinical population of Mashhad, Iran

Purpose To investigate the frequency of convergence and accommodation anomalies in an optometric clinical setting in Mashhad, Iran, and to determine tests with highest accuracy in diagnosing these anomalies. Methods From 261 patients who came to the optometric clinics of Mashhad University of Medical Sciences during a month, 83 of them were included in the study based on the inclusion criteria. Near point of convergence (NPC), near and distance heterophoria, monocular and binocular accommodative facility (MAF and BAF, respectively), lag of accommodation, positive and negative fusional vergences (PFV and NFV, respectively), AC/A ratio, relative accommodation, and amplitude of accommodation (AA) were measured to diagnose the convergence and accommodation anomalies. The results were also compared between symptomatic and asymptomatic patients. The accuracy of these tests was explored using sensitivity (S), specificity (Sp), and positive and negative likelihood ratios (LR+, LR−). Results Mean age of the patients was 21.3 ± 3.5 years and 14.5% of them had specific binocular and accommodative symptoms. Convergence and accommodative anomalies were found in 19.3% of the patients; accommodative excess (4.8%) and convergence insufficiency (3.6%) were the most common accommodative and convergence disorders, respectively. Symptomatic patients showed lower values for BAF (p = .003), MAF (p = .001), as well as AA (p = .001) compared with asymptomatic patients. Moreover, BAF (S = 75%, Sp = 62%) and MAF (S = 62%, Sp = 89%) were the most accurate tests for detecting accommodative and convergence disorders in terms of both sensitivity and specificity. Conclusions Convergence and accommodative anomalies are the most common binocular disorders in optometric patients. Including tests of monocular and binocular accommodative facility in routine eye examinations as accurate tests to diagnose these anomalies requires further investigation.

Association between single-nucleotide polymorphisms in growth factor genes and quality of life in men with prostate cancer and the general population

Purpose Improved survival for men with prostate cancer has led to increased attention to factors influencing quality of life (QOL). As protein levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) have been reported to be associated with QOL in people with cancer, we sought to identify whether single-nucleotide polymorphisms (SNPs) of these genes were associated with QOL in men with prostate cancer. Methods Multiple linear regression of two data sets (including approximately 750 men newly diagnosed with prostate cancer and 550 men from the general population) was used to investigate SNPs of VEGF and IGF-1 (10 SNPs in total) for associations with QOL (measured by the SF-36v2 health survey). Results Men with prostate cancer who carried the minor ‘T’ allele for IGF-1 SNP rs35767 had higher mean Role-Physical scale scores (≥0.3 SD) compared to non-carriers (p < 0.05). While this association was not identified in men from the general population, one IGF-1 SNP rs7965399 was associated with higher mean Bodily Pain scale scores in men from the general population that was not found in men with prostate cancer. Men from the general population who carried the rare ‘C’ allele had higher mean Bodily Pain scale scores (≥0.3 SD) than non-carriers (p < 0.05). Conclusions Through identifying SNPs that are associated with QOL in men with prostate cancer and men from the general population, this study adds to the mapping of complex interrelationships that influence QOL and suggests a role for IGF-I in physical QOL outcomes. Future research may identify biomarkers associated with increased risk of poor QOL that could assist in the provision of pre-emptive support for those identified at risk.

Cross-cultural adaptation, reliability and validity of the Turkish version of the spine functional index

Background The Spine Functional Index (SFI) is a patient reported outcome measure with sound clinimetric properties and clinical viability for the determination of whole-spine impairment. To date, no validated Turkish version is available. The purpose of this study is to cross-culturally adapted the SFI for Turkish-speaking patients (SFI-Tk) and determine the psychometric properties of reliability, validity and factor structure in a Turkish population with spine musculoskeletal disorders. Methods The SFI English version was culturally adapted and translated into Turkish using a double forward and backward method according to established guidelines. Patients (n = 285, cervical = l29, lumbar = 151, cervical and lumbar region = 5, 73% female, age 45 ± 1) with spine musculoskeletal disorders completed the SFI-Tk at baseline and after a seven day period for test-retest reliability. For criterion validity the Turkish version of the Functional Rating Index (FRI) was used plus the Neck Disability Index (NDI) for cervical patients and the Oswestry Disability Index (ODI) for back patients. Additional psychometric properties were determined for internal consistency (Chronbach’s α), criterion validity and factor structure. Results There was a high degree of internal consistency (α = 0.85, item range 0.80-0.88) and test-retest reliability (r = 0.93, item range = 0.75-0.95). The factor analysis demonstrated a one-factor solution explaining 24.2% of total variance. Criterion validity with the ODI was high (r = 0.71, p < 0.001) while the FRI and NDI were fair (r = 0.52 and r = 0.58, respectively). The SFI-Tk showed no missing responses with the ‘half-mark’ option used in 11.75% of total responses by 77.9% of participants. Measurement error from SEM and MDC90 were respectively 2.96% and 7.12%. Conclusions The SFI-Tk demonstrated a one-factor solution and is a reliable and valid instrument. The SFI-Tk consists of simple and easily understood wording and may be used to assess spine region musculoskeletal disorders in Turkish speaking patients.