Health risk assessment and health risk management with special reference to sodium monofluoroacetate (1080) for Possum control in New Zealand

The principal use of sodium monofluoroacetate (1080) in New Zealand is to control brushtail possums (Trichosurus vulpecula). Aerial application of baits containing 1080 is the most common method used for large-scale control of possums. The use of 1080 attracts a great deal of controversy, in particular the effects on the environmental, non-target species, and the potential chronic effects in humans associated with environmental exposures. Although the nature of the acute toxicity of 1080 has been known for more than fifty years, little is known of its effects on humans, in particular its chronic effects to environmental exposures. A benchmark dose (BMD) as an alternative to a no-observed-adverse-effect-level (NOAEL) approach was investigated as a means to improve current health risk assessment values of 1080. Both approaches were investigated for three critical toxicological end points, namely cardiomyopathy, testicular toxicity and teratogenic effects identified from the few available critical studies. The calculated BMDs and lower-bound confidence limits (BMDLs) for the three end points were estimated using the Weibull, probit and quanntal linear models. A benchmark response (BMR) of 10% (extra risk) was chosen and the Akaike's information criterion (AIC) was used in selecting the appropriate model. The BMDL estimates derived were generally slightly higher but comparable to the corresponding NOAEL for those same endpoints. The computed BMD10 and BMDL10 for cardiomyopathy and testicular effects were 0.21 mg kg^(-1) bw^(-1) and 0.10 mg kg^(-1) bw^(-1) respectively. Tolerable Daily Intakes (TDIs) were derived using the NOAEL approach and the BMD methodology and applying an uncertainty factor of 3000. The resulting TDI using the BMDL were generally consistently slightly higher than those derived using the NOAEL approach. Based on the best fit of modelled dose-response data, a TDI of 0.03 μg kg^(-1) bw^(-1) day^(-1) is proposed for human health risk assessment. Two sets of Provisional Maximum Acceptable Values (PMA V) were derived using the highest concentration of 4.0 μg L^(-1)1080 found in water (N=1450), and using the maximum allowable concentration of2.0 μg L^(-1) of 1080 in water for adults (0.58 μg L^(-1) and 0.94 μg L^(-1) , respectively) and children (0.23 μg L^(-1) and 0.4 μg L^(-1), respectively). Parameters used in the derivation of PMA Vs were average weight, average quantity of water consumed, and proportion of total intake allocated to drinking water. The derived adult PMA V of 0.60 μg L^(-1)is proposed in revising the PMA V for 1080 in the Drinking Water Standards New Zealand. This value is 6-fold lower than the current PMA V of 3.5 μg L^(-1). Additional toxicology studies are recommended to meet the definition of a "complete database" and therefore estimating a more defensible TDI, and consequently a PMAV for 1080. Risk management approaches are consistent with the Ministry of Health's current precautionary approach. A PMA V of 0.60 μg L^(-1) in drinking water is recommended to consider it suitable for human consumption and that continuous monitoring be carried if the level of 1080 exceeds 50% of the proposed PMAV as a requirement for Priority 2 determinands in the Drinking Water Standards. Precautionary approach appears to be warranted and this was supported by information provided by the Public Health Units (PHU) where 1080 was permitted to be dropped onto drinking water catchments. The PHU s exercised precautionary measures by imposing appropriate conditions to suit local circumstances. As 1080 may likely remain an essential tool to contain tuberculosis spread by possums and to reduce possum damage to forests and crops until better methods of control are developed, a number of recommendations were proposed to protect public health

Distribution and genetic variation of hymenolepidid cestodes in murid rodents on the Canary Islands (Spain)

<p>Abstract</p> <p>Background</p> <p>In the Canary Islands there are no previous data about tapeworms (Cestoda) of rodents. In order to identify the hymenolepidid species present in these hosts, a survey of 1,017 murine (349 <it>Rattus rattus</it>, 13 <it>Rattus norvegicus </it>and 655 <it>Mus musculus domesticus</it>) was carried out in the whole Archipelago. Molecular studies based on nuclear <it>ITS1 </it>and mitochondrial <it>COI </it>loci were performed to confirm the identifications and to analyse the levels of genetic variation and differentiation.</p> <p>Results</p> <p>Three species of hymenolepidids were identified: <it>Hymenolepis diminuta</it>, <it>Rodentolepis microstoma </it>and <it>Rodentolepis fraterna</it>. <it>Hymenolepis diminuta </it>(in rats) and <it>R. microstoma </it>(in mice) showed a widespread distribution in the Archipelago, and <it>R. fraterna </it>was the least spread species, appearing only on five of the islands. The hymenolepidids found on Fuerteventura, Lanzarote and La Graciosa were restricted to one area. The <it>COI </it>network of <it>H. diminuta </it>showed that the haplotypes from Lanzarote and Fuerteventura are the most distant with respect to the other islands, but clearly related among them.</p> <p>Conclusions</p> <p>Founder effects and biotic and abiotic factors could have played important role in the presence/absence of the hymenolepidid species in determined locations. The haplotypes from the eastern islands (Fuerteventura and Lanzarote) seem to have shared an ancestral haplotype very distant from the most frequent one that was found in the rest of the islands. Two colonization events or a single event with subsequent isolation and reduced gene flow between western-central and eastern islands, have taken place in the Archipelago. The three tapeworms detected are zoonotic species, and their presence among rodents from this Archipelago suggests a potential health risk to human via environmental contamination in high risk areas. However, the relatively low prevalence of infestations detected and the focal distribution of some of these species on certain islands reduce the general transmission risk to human.</p

Local magnetism and spin dynamics of the frustrated honeycomb rhodate Li2RhO3

We reportmagnetization, heat capacity, 7Li nuclear magnetic resonance (NMR), and muon-spin rotation (μSR) measurements on the honeycomb 4d5 spin liquid candidate Li2RhO3. The magnetization in small magnetic fields provides evidence of the partial spin-freezing of a small fraction of Rh4+ moments at 6 K, whereas the Curie-Weiss behavior above 100 K suggests a pseudo-spin-1/2 paramagnet with a moment of about 2.2μB. The magnetic specific heat (Cm) exhibits no field dependence and demonstrates the absence of long-range magnetic order down to 0.35 K. Cm/T passes through a broad maximum at about 10 K and Cm ∝ T 2 at low temperatures. Measurements of the spin-lattice relaxation rate (1/T1) reveal a gapless slowing-down of spin fluctuations upon cooling with 1/T1 ∼ T 2.2. The results from NMR and μSR are consistent with a scenario in which a minority of Rh4+ moments are in a short-range correlated frozen state and coexist with a majority of moments in a liquid-like state that continue to fluctuate at low temperatures

Magnetotransport in p-type Ge quantum well narrow wire arrays

We report magnetotransport measurements of a SiGe heterostructure containing a 20 nm p-Ge quantum well with a mobility of 800 000 cm2 V−1 s−1. By dry etching arrays of wires with widths between 1.0 μm and 3.0 μm, we were able to measure the lateral depletion thickness, built-in potential, and the phase coherence length of the quantum well. Fourier analysis does not show any Rashba related spin-splitting despite clearly defined Shubnikov-de Haas oscillations being observed up to a filling factor of ν = 22. Exchange-enhanced spin-splitting is observed for filling factors below ν = 9. An analysis of boundary scattering effects indicates lateral depletion of the hole gas by 0.5 ± 0.1 μm from the etched germanium surface. The built-in potential is found to be 0.25 ± 0.04 V, presenting an energy barrier for lateral transport greater than the hole confinement energy. A large phase coherence length of 3.5 ± 0.5 μm is obtained in these wires at 1.7 K.This work was supported by the EPSRC funded “Spintronic device physics in Si/Ge heterostructures” EP/J003263/1 and EP/J003638/1 projects and a Platform Grant No. EP/J001074/1.This is the author accepted manuscript. The final version is available from AIP via http://dx.doi.org/10.1063/1.4919053

Tankyrase inhibition sensitizes cells to CDK4 blockade

Tankyrase (TNKS) 1/2 are positive regulators of WNT signaling by controlling the activity of the ss-catenin destruction complex. TNKS inhibitors provide an opportunity to suppress hyperactive WNT signaling in tumors, however, they have shown limited anti-proliferative activity as a monotherapy in human cancer cell lines. Here we perform a kinome-focused CRISPR screen to identify potential effective drug combinations with TNKS inhibition. We show that the loss of CDK4, but not CDK6, synergizes with TNKS1/2 blockade to drive G1 cell cycle arrest and senescence. Through precise modelling of cancer-associated mutations using cytidine base editors, we show that this therapeutic approach is absolutely dependent on suppression of canonical WNT signaling by TNKS inhibitors and is effective in cells from multiple epithelial cancer types. Together, our results suggest that combined WNT and CDK4 inhibition might provide a potential therapeutic strategy for difficult-to-treat epithelial tumors

Statistical Analysis in Database of Offshore Naturally Flowing Wells with Abnormal Events

The development of statistical analysis in the oil and gas industry database represents the importance of seeking improvements in safety and preventing undesirable events. For accident prevention, which may cause damage to the environment and financial losses, fault detection is essential. Modern techniques on the data-driven, such as data analysis and artificial intelligence are currently considered the best options for this purpose. Regardless of advances in techniques for database manipulation, scientists spend an amount of time working on data quality improvement. Thus, the high dimensionality of data introduces computational and statistical challenges such as acquisition, treatment, processing and interpretation of data. In this paper, we used the 3W public dataset published by Vargas et al. (2019), provided by Petróleo Brasileiro S.A. (Petrobras), which contains 8 variables such as pressure, temperature and flow rate in the process of offshore natural flow wells. The database was evaluated by data exploration and transformation that enables statistical analysis. The relationship between the variables was verified using histograms, Spearman's correlation and Principal Component Analysis (PCA). The results showed that at least one variable should be removed and others should be filled in order to complete the database. The analysis, also, revealed that the variables do not follow a normal distribution, and the variables importance rank. Thereby, it was possible to reach a database with useful format

Controlling magnetic order and quantum disorder in molecule-based magnets.

We investigate the structural and magnetic properties of two molecule-based magnets synthesized from the same starting components. Their different structural motifs promote contrasting exchange pathways and consequently lead to markedly different magnetic ground states. Through examination of their structural and magnetic properties we show that [Cu(pyz)(H 2 O)(gly) 2 ](ClO 4 ) 2 may be considered a quasi-one-dimensional quantum Heisenberg antiferromagnet whereas the related compound [Cu(pyz)(gly)](ClO 4 ) , which is formed from dimers of antiferromagnetically interacting Cu 2+ spins, remains disordered down to at least 0.03 K in zero field but shows a field-temperature phase diagram reminiscent of that seen in materials showing a Bose-Einstein condensation of magnons