Ecological risk assessment of persistent organic pollutants in wetlands of the remediated Sydney Olympic Park, NSW, Australia

University of Technology, Sydney. Faculty of Science.Disruption to the endocrine systems of wild fauna by anthropogenic compounds (endocrine disruption) has received significant scientific attention over the past 50 years. Compounds with reported reproductive effects (e.g., natural and synthetic estrogens, organochlorine pesticides) have received particular attention due to their potential population level effects. Endocrine disruptors which bind to the aryl hydrocarbon receptor (AhR) (e.g., polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs)) are being increasingly studied. The toxic action of these compounds can be directly (by endogenous metabolisation to mutagenic products) or indirectly (causing carcinogenesis) mediated by the AhR. The presence of these compounds in the environment is cause for ecological concern. The manufacture and/or release of many endocrine disruptors (particularly chlorinated aromatic compounds) have been restricted in many countries but, due to their long half-lives, significant concentrations are still present in the environment. Sydney Olympic Park (SOP) is constructed on remediated land. Prior to remediation there were significant concentrations of persistent organic pollutants (POPs) (PCBs, PCDDs, organochlorine pesticides) on the site. The remediation effort in the lead-up to the Sydney Olympic Games in 2000 involved the excavation and treatment of large volumes of POP contaminated soil and sediment, and storage of treated and translocated wastes in containment mounds on the site. A number of wetlands was created during the restoration process and the area is now habitat for native and migratory fauna. It is also an area of high recreational and educational amenity. This research investigates the presence of endocrine disrupting chemicals (EDCs) in SOP in the post-remediation context. The studies in this research project investigate different lines of evidence from the concentrations of these chemicals, to in vitro bioassays, to an in vivo biomarker of exposure, to population and community level assessment of the presence and effects of POPs in the wetlands within the Park. The results of these individual studies form the basis of a weight-of-evidence semi-quantitative ranking of the wetlands within a gradient of contamination at reference sites. There was no evidence in the water of the wetlands in SOP to support the presence of EDCs with affinity for estrogen receptor (ER) (17β-estradiol equivalency (E2eq) quantified by an estrogen receptor radioligand binding assay). In the sediments of the wetlands there was quantifiable E2eq but there was no effect of this potential estrogenicity on the reproductive morphology of the male mosquitofish, Gambusia holbrooki. Chemical analysis showed measurable concentrations of ΣPAHs (272 – 14461 ng/g dry weight), ΣDDT (4 – 98 ng/g) and ΣPCBs (5 – 47 ng/g) within the sediments of most of the wetlands in SOP and an in vitro bioassay (H4IIE) indicated the presence of compounds able to bind to the AhR in all sediment samples (0.016 – 7.06 ng/g). Both the chemical and in vitro bioassay data for sites within SOP were within the range measured for urban impacted sites throughout Sydney. A biomarker of exposure to POPs (CYP1A induction) was measured in fish (mosquitofish) populations inhabiting the wetlands of SOP and was found to be significantly increased above basal level (2308 pmol res/min/mg protein) at one study site (Boundary Ck) (4327 pmol res/min/mg protein). When compared to reference sites around Sydney these were within the range measured at urban reference sites (1211 – 7579 pmol res/min/mg protein). Benthic macroinvertebrate communities were relatively depauperate in most wetlands and had low taxon richness. While it was not possible to assign the cause of these effects to the presence of organic pollutants, multivariate analysis of the data suggests a correlation between depauperate communities and increasing sediment concentrations of 2,3,7,8- tetrachlorodibenzo-p-dioxin equivalency (TCDDeq), ΣDDT and Total Organic Carbon. It was not possible to prove that differences between the life-history traits of mosquitofish inhabiting the study sites were due to POP-contamination. Differences are likely to be due to complex interactions of biotic and abiotic factors A weight-of-evidence approach synthesising these lines of evidence was developed to semi-quantitatively assess the ecological risk associated with the presence of POPs in SOP. A ranking of the sites revealed that the study sites within SOP fell between the pristine site (Upper Colo) and the heavily POP impacted reference site (Homebush Bay). It was concluded that there appears to be little or no legacy impact of the pre-remediation contamination levels at SOP. The remediation program has, therefore, been successful in returning SOP wetlands to within the chemical and biological bounds expected in an urban impacted wetland. Measured contamination in the created wetlands in SOP suggests current inputs from the catchment. It is recommended that these findings form the basis of ongoing monitoring, particularly of the most POP-affected wetlands, as identified by the weight-of evidence assessment (Boundary Ck and Lake Belvedere). Further, it is recommended that current sources of POPs in the urbanised catchments upstream of these sites be investigated and these contamination pathways restricted or closed

The Accidental Terrorist: Okhrana Connections to the Extreme-Right and the Attempt to Assassinate Sergei Witte in 1907

This article represents a case study in the relationship between the tsarist secret police (commonly known as the Okhrana in the West and okhranka in Russia) and acts of political terror perpetrated by the extreme-right in late imperial Russia. This specific case concerns the tangled web of conspiracy, propaganda and controversy that surrounded the attempted assassination of former-Chairman of the Council of Ministers, Sergei Witte, in 1907

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators

Mapping the decision pathways of acute infection management in secondary care among UK medical physicians: a qualitative study.

BACKGROUND: The inappropriate use of antimicrobials drives antimicrobial resistance. We conducted a study to map physician decision-making processes for acute infection management in secondary care to identify potential targets for quality improvement interventions. METHODS: Physicians newly qualified to consultant level participated in semi-structured interviews. Interviews were audio recorded and transcribed verbatim for analysis using NVIVO11.0 software. Grounded theory methodology was applied. Analytical categories were created using constant comparison approach to the data and participants were recruited to the study until thematic saturation was reached. RESULTS: Twenty physicians were interviewed. The decision pathway for the management of acute infections follows a Bayesian-like step-wise approach, with information processed and systematically added to prior assumptions to guide management. The main emerging themes identified as determinants of the decision-making of individual physicians were (1) perceptions of providing 'optimal' care for the patient with infection by providing rapid and often intravenous therapy; (2) perceptions that stopping/de-escalating therapy was a senior doctor decision with junior trainees not expected to contribute; and (3) expectation of interactions with local guidelines and microbiology service advice. Feedback on review of junior doctor prescribing decisions was often lacking, causing frustration and confusion on appropriate practice within this cohort. CONCLUSION: Interventions to improve infection management must incorporate mechanisms to promote distribution of responsibility for decisions made. The disparity between expectations of prescribers to start but not review/stop therapy must be urgently addressed with mechanisms to improve communication and feedback to junior prescribers to facilitate their continued development as prudent antimicrobial prescribers

Integrating Multiple Biomarkers of Fish Health: A Case Study of Fish Health in Ports

Biomarkers of fish health are recognised as valuable biomonitoring tools that inform on the impact of pollution on biota. The integration of a suite of biomarkers in a statistical analysis that better illustrates the effects of exposure to xenobiotics on living organisms is most informative; however, most published ecotoxicological studies base the interpretation of results on individual biomarkers rather than on the information they carry as a set. To compare the interpretation of results from individual biomarkers with an interpretation based on multivariate analysis, a case study was selected where fish health was examined in two species of fish captured in two ports located in Western Australia. The suite of variables selected included chemical analysis of white muscle, body condition index, liver somatic index (LSI), hepatic ethoxyresorufin-O-deethylase activity, serum sorbitol dehydrogenase activity, biliary polycyclic aromatic hydrocarbon metabolites, oxidative DNA damage as measured by serum 8-oxo-dG, and stress protein HSP70 measured on gill tissue. Statistical analysis of individual biomarkers suggested little consistent evidence of the effects of contaminants on fish health. However, when biomarkers were integrated as a set by principal component analysis, there was evidence that the health status of fish in Fremantle port was compromised mainly due to increased LSI and greater oxidative DNA damage in fish captured within the port area relative to fish captured at a remote site. The conclusions achieved using the integrated set of biomarkers show the importance of viewing biomarkers of fish health as a set of variables rather than as isolated biomarkers of fish health

Cost-Effectiveness of Peer-Delivered Interventions for Cocaine and Alcohol Abuse among Women: A Randomized Controlled Trial

<div><h3>Aims</h3><p>To determine whether the additional interventions to standard care are cost-effective in addressing cocaine and alcohol abuse at 4 months (4 M) and 12 months (12 M) from baseline.</p> <h3>Method</h3><p>We conducted a cost-effectiveness analysis of a randomized controlled trial with three arms: (1) NIDA's Standard intervention (SI); (2) SI plus a Well Woman Exam (WWE); and, (3) SI, WWE, plus four Educational Sessions (4ES).</p> <h3>Results</h3><p>To obtain an additional cocaine abstainer, WWE compared to SI cost $7,223 at 4 M and$3,611 at 12 M. Per additional alcohol abstainer, WWE compared to SI cost $3,611 and$7,223 at 4 M and 12 M, respectively. At 12 M, 4ES was dominated (more costly and less effective) by WWE for abstinence outcomes.</p> <h3>Conclusions</h3><p>To our knowledge, this is the first cost-effectiveness analysis simultaneously examining cocaine and alcohol abuse in women. Depending on primary outcomes sought and priorities of policy makers, peer-delivered interventions can be a cost-effective way to address the needs of this growing, underserved population.</p> <h3>Trial Registration</h3><p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01235091">NCT01235091</a></p> </div

An Integrative Design Framework for New Service Development

Service innovation is focused on customer value creation. At its core, customer-centric service innovation in an increasingly digital world is technology-enabled, human-centered, and process-oriented. This requires a cross-disciplinary, holistic approach to new service design and development (NSD). This paper proposes a new service strategy-aligned integrative design framework for NSD. It correlates the underlying theories and principles of disparate but interrelated aspects of service design thinking: service strategy, concept, design, experience and architecture into a coherent framework for NSD, consistent with the service brand value. Application of the framework to NSD is envisioned to be iterative and holistic, accentuated on continuous organizational and customer learning. The preliminary framework's efficacy is illustrated using a simplified telecom case example. © Springer International Publishing Switzerland 2014

Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients

BACKGROUND: In colorectal cancer (CRC), tumour microsatellite instability (MSI) status and CpG island methylator phenotype (CIMP) status are indicators of patient outcome, but the molecular events that give rise to these outcomes remain largely unknown. Wnt5a is a critical regulator of non-canonical Wnt activity and promoter hypermethylation of this gene has emerging prognostic roles in CRC; however the frequency and prognostic significance of this epigenetic event have not been explored in the context of colorectal tumour subtype. Consequently, we investigated the frequency and prognostic significance of Wnt5a methylation in a large cohort of MSI-stratified CRCs. METHODS: Methylation was quantified in a large cohort of 1232 colorectal carcinomas from two clinically distinct populations from Canada. Associations were examined between methylation status and clinicopathlogical features, including tumour MSI status, BRAF V600E mutation, and patient survival. RESULTS: In Ontario, Wnt5a methylation was strongly associated with MSI tumours after adjustment for age, sex, and tumour location (odds ratio (OR)=4.2, 95% confidence interval (CI)=2.4-7.4, P<10(-6)) and with BRAF V600E mutation, a marker of CIMP (OR=12.3, 95% CI=6.9-21.7, P<10(-17)), but was not associated with patient survival. Concordant results were obtained in Newfoundland. CONCLUSION: Methylation of Wnt5a is associated with distinct tumour subtypes, strengthening the evidence of an epigenetic-mediated Wnt bias in CRC

A Severe Lack of Evidence Limits Effective Conservation of the World's Primates

Threats to biodiversity are well documented. However, to effectively conserve species and their habitats, we need to know which conservation interventions do (or do not) work. Evidence-based conservation evaluates interventions within a scientific framework. The Conservation Evidence project has summarized thousands of studies testing conservation interventions and compiled these as synopses for various habitats and taxa. In the present article, we analyzed the interventions assessed in the primate synopsis and compared these with other taxa. We found that despite intensive efforts to study primates and the extensive threats they face, less than 1% of primate studies evaluated conservation effectiveness. The studies often lacked quantitative data, failed to undertake postimplementation monitoring of populations or individuals, or implemented several interventions at once. Furthermore, the studies were biased toward specific taxa, geographic regions, and interventions. We describe barriers for testing primate conservation interventions and propose actions to improve the conservation evidence base to protect this endangered and globally important taxon

Progress in the management and outcome of small-cell lung cancer in a French region from 1981 to 1994

Recent analyses of series of small-cell lung cancer (SCLC) patients included in clinical trials have shown improved survival over time, but it has been impossible to determine whether this was due to selection biases, stage migration, or true therapeutic improvement. To determine if there has been a true improvement of survival over time, we reviewed the medical records of all consecutive patients diagnosed with SCLC between 1981 and 1994 in the Bas-Rhin in France. Among the 787 patients (median age 63), there was no significant period effect for sex, age, or stage. Staging work-ups became increasingly thorough (significant period effect). The mean number of investigations and of tumour sites detected correlated significantly. The chemotherapy rate increased (from 76.4% in 1981–1983 to 91.7% in 1993–1994, P = 10−5) and mediastinal irradiation decreased (to roughly 25% of patients after 1983). Median survival time increased for the overall population from 6.6 months in 1981–1983 to 11.3 months in 1993–1994 (P = 10−5), for patients with limited disease (LD) from 9.2 (P = 0.002) months to 14.0 months, and for those with extensive (ED) disease from 3.5 months to 9.6 months (P = 10−5). Significant independent prognostic factors were disease extent, clinical trial participation, period, type of chemotherapy, and mediastinal irradiation in LD. Survival time has truly improved as ‘state of the art' management of SCLC has changed. © 2001 Cancer Research Campaignhttp://www.bjcancer.co