Effect of spatial variation on salinity tolerance of macroinvertebrates in Eastern Australia and implications for ecosystem protection trigger values

Salinisation of freshwater has been identified as a serious environmental issue in Australia and around the world. Protective concentrations (trigger values) for salinity can be used to manage salinity impacts, though require locally relevant salinity tolerance information. 72-h acute salinity tolerance values were determined for 102 macroinvertebrates collected from 11 locations in four biologically distinct freshwater bio-regions in Northeast Australia and compared with sensitivities observed in Southeast Australia. The salinity tolerance of individual taxa was consistent across Northeast Australia and between Northeast and Southeast Australia. However, two distinct communities were identified in Northeast Australia using distributions of the acute tolerance values and a calculated index of salinity sensitivity. Salinity trigger values should therefore be representative of local or regionally relevant communities and may be adequately calculated using sensitivity values from throughout Eastern Australia. The results presented provide a basis for assessing salinity risk and determining trigger values for salinity in freshwater ecosystems at local and regional scales in Eastern Australia. Crown Copyrigh

Do contaminants originating from state-of-the-art treated wastewater impact the ecological quality of surface waters?

Since the 1980s, advances in wastewater treatment technology have led to considerably improved surface water quality in the urban areas of many high income countries. However, trace concentrations of organic wastewater-associated contaminants may still pose a key environmental hazard impairing the ecological quality of surface waters. To identify key impact factors, we analyzed the effects of a wide range of anthropogenic and environmental variables on the aquatic macroinvertebrate community. We assessed ecological water quality at 26 sampling sites in four urban German lowland river systems with a 0–100% load of state-of-the-art biological activated sludge treated wastewater. The chemical analysis suite comprised 12 organic contaminants (five phosphor organic flame retardants, two musk fragrances, bisphenol A, nonylphenol, octylphenol, diethyltoluamide, terbutryn), 16 polycyclic aromatic hydrocarbons, and 12 heavy metals. Non-metric multidimensional scaling identified organic contaminants that are mainly wastewater-associated (i.e., phosphor organic flame retardants, musk fragrances, and diethyltoluamide) as a major impact variable on macroinvertebrate species composition. The structural degradation of streams was also identified as a significant factor. Multiple linear regression models revealed a significant impact of organic contaminants on invertebrate populations, in particular on Ephemeroptera, Plecoptera, and Trichoptera species. Spearman rank correlation analyses confirmed wastewater-associated organic contaminants as the most significant variable negatively impacting the biodiversity of sensitive macroinvertebrate species. In addition to increased aquatic pollution with organic contaminants, a greater wastewater fraction was accompanied by a slight decrease in oxygen concentration and an increase in salinity. This study highlights the importance of reducing the wastewater-associated impact on surface waters. For aquatic ecosystems in urban areas this would lead to: (i) improvement of the ecological integrity, (ii) reduction of biodiversity loss, and (iii) faster achievement of objectives of legislative requirements, e.g., the European Water Framework Directive

Effects of salinity on leaf breakdown: dryland salinity versus salinity from a coalmine

Salinization of freshwater ecosystems as a result of human activities represents a global threat for ecosystems’ integrity. Whether different sources of salinity with their differing ionic compositions lead to variable effects in ecosystem functioning is unknown. Therefore, the present study assessed the impact of dryland- (50\ua0μS/cm to 11,000\ua0μS/cm) and coalmine-induced (100\ua0μS/cm to 2400\ua0μS/cm) salinization on the leaf litter breakdown, with focus on microorganisms as main decomposer, in two catchments in New South Wales, Australia. The breakdown of Eucalyptus camaldulensis leaves decreased with increasing salinity by up to a factor of three. Coalmine salinity, which is characterised by a higher share of bicarbonates, had a slightly but consistently higher breakdown rate at a given salinity relative to dryland salinity, which is characterised by ionic proportions similar to sea water. Complementary laboratory experiments supported the stimulatory impact of sodium bicarbonates on leaf breakdown when compared to sodium chloride or artificial sea salt. Furthermore, microbial inoculum from a high salinity site (11,000\ua0μS/cm) yielded lower leaf breakdown at lower salinity relative to inoculum from a low salinity site (50\ua0μS/cm). Conversely, inoculum from the high salinity site was less sensitive towards increasing salinity levels relative to inoculum from the low salinity site. The effects of the different inoculum were the same regardless of salt source (sodium bicarbonate, sodium chloride and artificial sea salt). Finally, the microorganism-mediated leaf litter breakdown was most efficient at intermediate salinity levels (≈500\ua0μS/cm). The present study thus points to severe implications of increasing salinity intensities on the ecosystem function of leaf litter breakdown, while the underlying processes need further scrutiny

Data-driven campaigning and democratic disruption : evidence from six advanced democracies

Data-driven campaigning has become one of the key foci for academic and non-academic audiences interested in political communication. Widely seen to have transformed political practice, it is often argued that data-driven campaigning is a force of significant democratic disruption because it contributes to a fragmentation of political discourse, undermines prevailing systems of electoral accountability and subverts ‘free’ and ‘fair’ elections. In this article, we present one of the very first cross-national analyses of data-driven campaigning by political parties. Drawing on empirical research conducted by experts in six advanced democracies, we show that the data-driven campaign practices seen to threaten democracy are often not manifest in party campaigns. Instead, we see a set of practices that build on pre-existing techniques and which are far less sophisticated than is often assumed. Indeed, we present evidence that most political parties lack the capacity to execute the hyper-intensive practices often associated with data-driven campaigning. Hence, while there is reason to remain alert to the challenges data-driven campaigning produces for democratic norms, we argue that this practice is not inherently disruptive, but rather exemplifies the evolving nature of political campaigning in the 21st century

Efficacy of novel immunotherapy regimens in patients with metastatic melanoma with germline CDKN2A mutations

Inherited CDKN2A mutation is a strong risk factor for cutaneous melanoma. Moreover, carriers have been found to have poor melanoma-specific survival. In this study, responses to novel immunotherapy agents in CDKN2A mutation carriers with metastatic melanoma were evaluated

Targeting BRAF for patients with melanoma

The prognosis of patients with metastatic melanoma is poor and not influenced by systemic therapy with cytotoxic drugs. New targeted agents directed against the RAS-RAF-MEK-ERK pathway show promising activity in early clinical development and particular interest is focused on selective inhibitors of mutant BRAF, which is present in one half of the cases of metastatic melanoma. The majority of patients on early trials of these drugs develop secondary resistance and subsequent disease progression and it is, therefore, critical to understand the underlying escape mechanisms leading to resistance

Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study

<p><b>Background</b> Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.</p> <p><b>Methods</b> We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.</p> <p><b>Results</b> Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10−6 ≤ P ≤ .02).</p> <p><b>Conclusion</b> Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.</p&gt

Randomized trial of the combination of lomeguatrib and temozolomide compared with temozolomide alone in chemotherapy naive patients with metastatic cutaneous melanoma

PURPOSE: To evaluate tumor response, pharmacodynamic effects, and safety of a combination of lomeguatrib (LM), an O6-methylguanine DNA-methyltransferase (MGMT) inactivator, and temozolomide (TMZ), TMZ alone, and LM/TMZ after disease progression on TMZ alone in patients with advanced melanoma. PATIENTS AND METHODS: Patients with unresectable stage III or IV cutaneous melanoma who had no prior systemic chemotherapy were randomly assigned to receive either 40 to 80 mg LM and 125 mg/m2 TMZ or 200 mg/m2 TMZ on days 1 through 5 of each 28-day treatment cycle. Drugs were administered orally for up to six cycles of treatment. Patients on TMZ alone were offered LM/TMZ at progression, if fit enough to receive treatment. RESULTS: One hundred four patients were enrolled, with 52 in each trial arm. Twenty-seven TMZ-treated patients received LM/TMZ after progression on TMZ. Unexpectedly, analysis of tumor biopsies showed rapid recovery of MGMT after LM/TMZ with 40 mg/d LM. Therefore, doses of LM were escalated to 60 then 80 mg/d. Tumor response rates were 13.5% with LM/TMZ and 17.3% with TMZ alone. No patient responded to LM/TMZ having progressed through TMZ. Median time to disease progression was 65.5 days for LM/TMZ and 68 days for TMZ. All treatments were well tolerated, although hematologic and gastrointestinal adverse events were common. A higher incidence of hematological adverse events was observed in the LM/TMZ combination arm. CONCLUSION: The efficacy of LM and TMZ in the current dosing schedule is similar to that of TMZ alone. To maintain MGMT depletion in tumor dosing of LM needs to be continued beyond that of TMZ