Molecular docking and geographical information systems as tools to assess the potential impact of veterinary medicines on non-target organisms and the environment

Veterinary medicines (VMs) from agricultural industry can enter the environment in a number of ways. This includes direct exposure through aquaculture, accidental spillage and disposal, and indirect entry by leaching from manure or runoff after treatment. Many compounds used in animal treatments have ecotoxic properties that may have chronic or sometimes lethal effects when they come into contact with non-target organisms. VMs enter the environment in mixtures, potentially having additive effects. Traditional ecotoxicology tests are used to determine the lethal and sometimes reproductive effects on freshwater and terrestrial organisms. However, organisms used in ecotoxicology tests can be unrepresentative of the populations that are likely to be exposed to the compound in the environment. Most often the tests are on single compound toxicity but mixture effects may be significant and should be included in ecotoxicology testing. This work investigates the use, measured environmental concentrations (MECs) and potential impact of sea lice treatments on salmon farms in Scotland. Alternative methods for ecotoxicology testing including mixture toxicity, and the use of in silico techniques to predict the chronic impact of VMs on different species of aquatic organisms were also investigated. The Scottish Environmental Protection Agency (SEPA) provided information on the use of five sea lice treatments from 2008-2011 on Scottish salmon farms. This information was combined with the recently available data on sediment MECs for the years 2009-2012 provided by SEPA using ArcGIS 10.1. In depth analysis of this data showed that from a total of 55 sites, 30 sites had a MEC higher than the maximum allowable concentration (MAC) as set out by SEPA for emamectin benzoate and 7 sites had a higher MEC than MAC for teflubenzuron. A number of sites that were up to 16 km away from the nearest salmon farm reported as using either emamectin benzoate or teflubenzuron measured positive for the two treatments. There was no relationship between current direction and the distribution of the sea lice treatments, nor was there any evidence for alternative sources of the compounds e.g. land treatments. The sites that had MECs higher than the MAC could pose a risk to non-target organisms and disrupt the species dynamics of the area. There was evidence that some marine protected sites might be at risk of exposure to these compounds. To complement this work, effects on acute mixture toxicity of the 5 sea lice treatments, plus one major metabolite 3-phenoxybenzoic acid (3PBA), were measured using an assay using the bioluminescent bacteria Aliivibrio fischeri. When exposed to the 5 sea lice treatments and 3PBA A. fischeri showed a response to 3PBA, emamectin benzoate and azamethiphos as well as combinations of the three. In order to establish any additive effect of the sea lice treatments, the efficacy of two mixture prediction equations, concentration addition (CA) and independent action ii(IA) were tested using the results from single compound dose response curves. In this instance IA was the more effective prediction method with a linear regression confidence interval of 82.6% compared with 22.6% of CA. In silico molecular docking was carried out to predict the chronic effects of 15 VMs (including the five used as sea lice control). Molecular docking has been proposed as an alternative screening method for the chronic effects of large animal treatments on non-target organisms. Oestrogen receptor alpha (ERα) of 7 non-target bony fish and the African clawed frog Xenopus laevis were modelled using SwissModel. These models were then ‘docked’ to oestradiol, the synthetic oestrogen ethinylestradiol, two known xenoestrogens dichlorodiphenyltrichloroethane (DDT) and bisphenol A (BPA), the antioestrogen breast cancer treatment tamoxifen and 15 VMs using Auto Dock 4. Based on the results of this work, four VMs were identified as being possible xenoestrogens or anti-oestrogens; these were cypermethrin, deltamethrin, fenbendazole and teflubenzuron. Further investigation, using in vitro assays, into these four VMs has been suggested as future work. A modified recombinant yeast oestrogen screen (YES) was attempted using the cDNA of the ERα of the zebrafish Danio rerio and the rainbow trout Oncorhynchus mykiss. Due to time and difficulties in cloning protocols this work was unable to be completed. Use of such in vitro assays would allow for further investigation of the highlighted VMs into their oestrogenic potential. In conclusion, VMs used as sea lice treatments, such as teflubenzuron and emamectin benzoate may be more persistent and have a wider range in the environment than previously thought. Mixtures of sea lice treatments have been found to persist together in the environment, and effects of these mixtures on the bacteria A. fischeri can be predicted using the IA equation. Finally, molecular docking may be a suitable tool to predict chronic endocrine disrupting effects and identify varying degrees of impact on the ERα of nine species of aquatic organisms.

Commodification of health care systems: The Catalan case

Commodification of the public healthcare system has been a growing process in recent decades, especially in universal healthcare systems and in high-income countries like Spain.  There are substantial differences in the healthcare systems of each autonomous region of Spain, among which Catalonia is characterized by having a mixed healthcare system with complex partnerships and interactions between the public and private healthcare sectors.  Using a narrative review approach, this article addresses various aspects of the Catalan healthcare system, characterizing the privatization and commodification of health processes in Catalonia from a historical perspective with particular attention to recent legislative changes and austerity measures.  The article approximates, the eventual effects that commodification and austerity measures will have on the health of the population and on the structure, accessibility, effectiveness, equity and quality of healthcare services.

Damping Torque Analysis of Power Systems with DFIGs for Wind Power Generation

A grid-connected DFIG for wind power generation can affect power system small-signal angular stability in two ways: by changing the system load flow condition and dynamically interacting with synchronous generators (SGs). This paper presents the application of conventional method of damping torque analysis (DTA) to examine the effect of DFIG’s dynamic interactions with SGs on the small-signal angular stability. It shows that the effect is due to the dynamic variation of power exchange between the DFIG and power system and can be estimated approximately by the DTA. Consequently, if the DFIG is modelled as a constant power source when the effect of zero dynamic interactions is assumed, the impact of change of load flow brought about by the DFIG can be determined. Thus the total effect of DFIG can be estimated from the result of DTA added on that of constant power source model. Applications of the DTA method proposed in the paper are discussed. An example of multi-machine power systems with grid-connected DFIGs are presented to demonstrate and validate the DTA method proposed and conclusions obtained in the paper.

A multi vector energy analysis for interconnected power and gas systems

This paper presents the first multi vector energy analysis for the interconnected energy systems of Great Britain (GB) and Ireland. Both systems share a common high penetration of wind power, but significantly different security of supply outlooks. Ireland is heavily dependent on gas imports from GB, giving significance to the interconnected aspect of the methodology in addition to the gas and power interactions analysed. A fully realistic unit commitment and economic dispatch model coupled to an energy flow model of the gas supply network is developed. Extreme weather events driving increased domestic gas demand and low wind power output were utilised to increase gas supply network stress. Decreased wind profiles had a larger impact on system security than high domestic gas demand. However, the GB energy system was resilient during high demand periods but gas network stress limited the ramping capability of localised generating units. Additionally, gas system entry node congestion in the Irish system was shown to deliver a 40% increase in short run costs for generators. Gas storage was shown to reduce the impact of high demand driven congestion delivering a reduction in total generation costs of 14% in the period studied and reducing electricity imports from GB, significantly contributing to security of supply.

Preparation of low protein latex : Effect of different cure systems and fillers on its properties

Natural rubber latex, an aqueous colloidal dispersion of polyisoprene is widely used in production of gloves, catherers, rubber bands etc. The natural rubber latex content present in products such as gloves causes allergic problems. Of the different types of allergies reported, latex is known to produce Type I and Type IV allergies. Type I is called immediate hypersensitivity and type IV is called delayed hypersensitivity. It has been reported that some of the proteins present in the latex are mainly responsible for the allergic reactions type I. Significant reduction in the allergic response (type I) of natural rubber latex can be achieved by the reduction in its protein content, however out of the total proteins present in the latex or latex film only a fraction is extractable. The major techniques employed to reduce protein content of latex include leaching, autoclaving, chlorination, use of proteolytic enzymes and use of non ionic surfactants. Sulphur vulcanization of dipped products is responsible for Type IV allergy. N-nitrosamine, a carcinogenic substance is produced as a result of sulphur vulcanization. Radiation vulcanization can be used as an alternative for sulphur vulcanization. The current research deals with techniques to reduce the allergy associated with latex products. To reduce the type I allergy, low protein latex is developed using polyethylene glycol, a non- ionic surfactant. The present study employs radiation vulcanization to eliminate type IV allergy. The effect of different cure systems and fillers on the properties of low protein latex is also investigated as a part of the study.

Improving Patients’ Experience and Outcome of Total Joint Replacement: the RESTORE Programme

BACKGROUND: Total hip replacements (THRs) and total knee replacements (TKRs) are common elective procedures. In the REsearch STudies into the ORthopaedic Experience (RESTORE) programme, we explored the care and experiences of patients with osteoarthritis after being listed for THR and TKR up to the time when an optimal outcome should be expected. OBJECTIVE: To undertake a programme of research studies to work towards improving patient outcomes after THR and TKR. METHODS: We used methodologies appropriate to research questions: systematic reviews, qualitative studies, randomised controlled trials (RCTs), feasibility studies, cohort studies and a survey. Research was supported by patient and public involvement. RESULTS: Systematic review of longitudinal studies showed that moderate to severe long-term pain affects about 7–23% of patients after THR and 10–34% after TKR. In our cohort study, 10% of patients with hip replacement and 30% with knee replacement showed no clinically or statistically significant functional improvement. In our review of pain assessment few research studies used measures to capture the incidence, character and impact of long-term pain. Qualitative studies highlighted the importance of support by health and social professionals for patients at different stages of the joint replacement pathway. Our review of longitudinal studies suggested that patients with poorer psychological health, physical function or pain before surgery had poorer long-term outcomes and may benefit from pre-surgical interventions. However, uptake of a pre-operative pain management intervention was low. Although evidence relating to patient outcomes was limited, comorbidities are common and may lead to an increased risk of adverse events, suggesting the possible value of optimising pre-operative management. The evidence base on clinical effectiveness of pre-surgical interventions, occupational therapy and physiotherapy-based rehabilitation relied on small RCTs but suggested short-term benefit. Our feasibility studies showed that definitive trials of occupational therapy before surgery and post-discharge group-based physiotherapy exercise are feasible and acceptable to patients. Randomised trial results and systematic review suggest that patients with THR should receive local anaesthetic infiltration for the management of long-term pain, but in patients receiving TKR it may not provide additional benefit to femoral nerve block. From a NHS and Personal Social Services perspective, local anaesthetic infiltration was a cost-effective treatment in primary THR. In qualitative interviews, patients and health-care professionals recognised the importance of participating in the RCTs. To support future interventions and their evaluation, we conducted a study comparing outcome measures and analysed the RCTs as cohort studies. Analyses highlighted the importance of different methods in treating and assessing hip and knee osteoarthritis. There was an inverse association between radiographic severity of osteoarthritis and pain and function in patients waiting for TKR but no association in THR. Different pain characteristics predicted long-term pain in THR and TKR. Outcomes after joint replacement should be assessed with a patient-reported outcome and a functional test. CONCLUSIONS: The RESTORE programme provides important information to guide the development of interventions to improve long-term outcomes for patients with osteoarthritis receiving THR and TKR. Issues relating to their evaluation and the assessment of patient outcomes are highlighted. Potential interventions at key times in the patient pathway were identified and deserve further study, ultimately in the context of a complex intervention.

The Greek monetary system and its derivations over other ancient Mediterranean systems.

One of the main features of the Greek currency are the big differences between emissions of the polis, which did not match either in their iconographic message types, not even in the met-rical pattern of their values. These differences were reflected in exchange systems ruled by the main sanctuaries that shrines stipu-lated thus giving official status to change.

Energy systems analysis of transboundary river basins in a nexus approach: the Sava river basin study case

Resource management policies are frequently designed and planned to target specific needs of particular sectors, without taking into account the interests of other sectors who share the same resources. In a climate of resource depletion, population growth, increase in energy demand and climate change awareness, it is of great importance to promote the assessment of intersectoral linkages and, by doing so, understand their effects and implications. This need is further augmented when common use of resources might not be solely relevant at national level, but also when the distribution of resources ranges over different nations. This dissertation focuses on the study of the energy systems of five south eastern European countries, which share the Sava River Basin, using a water-food(agriculture)-energy nexus approach. In the case of the electricity generation sector, the use of water is essential for the integrity of the energy systems, as the electricity production in the riparian countries relies on two major technologies dependent on water resources: hydro and thermal power plants. For example, in 2012, an average of 37% of the electricity production in the SRB countries was generated by hydropower and 61% in thermal power plants. Focusing on the SRB, in terms of existing installed capacities, the basin accommodates close to a tenth of all hydropower capacity while providing water for cooling to 42% of the net capacity of thermal power currently in operation in the basin. This energy-oriented nexus study explores the dependency on the basin’s water resources of the energy systems in the region for the period between 2015 and 2030. To do so, a multi-country electricity model was developed to provide a quantification ground to the analysis, using the open-source software modelling tool OSeMOSYS. Three main areas are subject to analysis: first, the impact of energy efficiency and renewable energy strategies in the electricity generation mix; secondly, the potential impacts of climate change under a moderate climate change projection scenario; and finally, deriving from the latter point, the cumulative impact of an increase in water demand in the agriculture sector, for irrigation. Additionally, electricity trade dynamics are compared across the different scenarios under scrutiny, as an effort to investigate the implications of the aforementioned factors in the electricity markets in the region.

Use of closed systems in the Hospital Pharmacy

Objective: In the setting of the increasing use of closed systems for reconstitution and preparation of these drugs, we intend to analyze the correct use of these systems in the Hospital Pharmacy, with the objective to minimize the risks of exposure not only for those professionals directly involved, but also for all the staff in the unit, taking also into account efficiency criteria. Method: Since some systems protect against aerosol formation but not from vapours, we decided to review which cytostatics should be prepared using an awl with an air inlet valve, in order to implement a new working procedure. We reviewed the formulations available in our hospital, with the following criteria: method of administration, excipients, and potential hazard for the staff handling them. We measured the diameters of the vials. We selected drugs with Level 1 Risk and also those including alcohol-based excipients, which could generate vapours. Outcomes: Out of the 66 reviewed formulations, we concluded that 11 drugs should be reconstituted with this type of awl: busulfan, cabazitaxel, carmustine, cyclophosphamide, eribulin, etoposide, fotemustine, melphalan, paclitaxel, temsirolimus and thiotepa; these represented an 18% of the total volume of formulations. Conclusions: The selection of healthcare products must be done at the Hospital Pharmacy, because the use of a system with an air valve inlet only for those drugs selected led to an outcome of savings and a more efficient use of materials. In our experience, we confirmed that the use of the needle could only be avoided when the awl could adapt to the different formulations of cytostatics, and this is only possible when different types of awls are available. Besides, connections were only really closed when a single awl was used for each vial. The change in working methodology when handling these drugs, as a result of this study, will allow us to start different studies about environmental contamination as a future line of work.

Capacity analysis in CDMA systems using GIS based planning tools

We show a simulation model for capacity analysis in mobile systems using a geographic information system (GIS) based tool, used for coverage calculations and frequency assignment, and MATLAB. The model was developed initially for “narrowband” CDMA and TDMA, but was modified for WCDMA. We show also some results for a specific case in “narrowband” CDMA

Growth and development of three key summer grasses in Australian cotton systems

Awnless barnyard grass, feathertop Rhodes grass, and windmill grass are important weeds in Australian cotton systems. In October 2014, an experiment was established to investigate the phenological plasticity of these species. Seed of these species were planted in a glasshouse every four weeks and each cohort grown for 6 months. A developmental response to day length was observed in barnyard grass but not in the other species. Days to maturity increased with each planting for feathertop Rhodes and windmill grass for the first six cohorts. Barnyard grass showed a similar pattern in growth for seeds planted from October to December with an increase in the onset of maturity from 51 to 58 days. However, the onset of maturity for cohorts planted between January and March decreased to between 50 and 52 days. All species had a decrease in the total number of panicles produced from the first four plantings. Feathertop Rhodes grass planted in October produced 41 panicles compared to those planted at the end of December producing 30 panicles, barnyard grass had a decrease from 99 to 47 panicles and windmill grass 37 to 15 panicles on average. By comparing the development of these key weed species over 12 months, detailed information on the phenological plasticity of these species will be obtained. This information will contribute to more informed management decisions by improving our understanding of appropriate weed control timings or herbicide rates depending on weed emergence and development.

Elucidating the interactions between the adhesive and transcriptioanl functions of beta-catenin in normal and cancerous cells

Wnt signalling is involved in a wide range of physiological and pathological processes. The presence of an extracellular Wnt stimulus induces cytoplasmic stabilisation and nuclear translocation of beta-catenin, a protein that also plays an essential role in cadherin-mediated adhesion. Two main hypotheses have been proposed concerning the balance between beta-catenin's adhesive and transcriptional functions: either beta-catenin's fate is determined by competition between its binding partners, or Wnt induces folding of beta-catenin into a conformation allocated preferentially to transcription. The experimental data supporting each hypotheses remain inconclusive. In this paper we present a new mathematical model of the Wnt pathway that incorporates beta-catenin's dual function. We use this model to carry out a series of in silico experiments and compare the behaviour of systems governed by each hypothesis. Our analytical results and model simulations provide further insight into the current understanding of Wnt signalling and, in particular, reveal differences in the response of the two modes of interaction between adhesion and signalling in certain in silico settings. We also exploit our model to investigate the impact of the mutations most commonly observed in human colorectal cancer. Simulations show that the amount of functional APC required to maintain a normal phenotype increases with increasing strength of the Wnt signal, a result which illustrates that the environment can substantially influence both tumour initiation and phenotype.

Effect of sugarcane cropping systems on herbicide losses in surface runoff

Herbicide runoff from cropping fields has been identified as a threat to the Great Barrier Reef ecosystem. A field investigation was carried out to monitor the changes in runoff water quality resulting from four different sugarcane cropping systems that included different herbicides and contrasting tillage and trash management practices. These include (i) Conventional - Tillage (beds and inter-rows) with residual herbicides used; (ii) Improved - only the beds were tilled (zonal) with reduced residual herbicides used; (iii) Aspirational - minimum tillage (one pass of a single tine ripper before planting) with trash mulch, no residual herbicides and a legume intercrop after cane establishment; and (iv) New Farming System (NFS) - minimum tillage as in Aspirational practice with a grain legume rotation and a combination of residual and knockdown herbicides. Results suggest soil and trash management had a larger effect on the herbicide losses in runoff than the physico-chemical properties of herbicides. Improved practices with 30% lower atrazine application rates than used in conventional systems produced reduced runoff volumes by 40% and atrazine loss by 62%. There were a 2-fold variation in atrazine and >10-fold variation in metribuzin loads in runoff water between reduced tillage systems differing in soil disturbance and surface residue cover from the previous rotation crops, despite the same herbicide application rates. The elevated risk of offsite losses from herbicides was illustrated by the high concentrations of diuron (14mugL-1) recorded in runoff that occurred >2.5months after herbicide application in a 1st ratoon crop. A cropping system employing less persistent non-selective herbicides and an inter-row soybean mulch resulted in no residual herbicide contamination in runoff water, but recorded 12.3% lower yield compared to Conventional practice. These findings reveal a trade-off between achieving good water quality with minimal herbicide contamination and maintaining farm profitability with good weed control.

Use of Products and Systems for Scientific and Technical College Education and Development for Industrial

Have been less than thirty years since a group of graduate students and computer scientists working on a federal contract performed the first successful connection between two computers located at remote sites. This group known as the NWG Network Working Group, comprised of highly creative geniuses who as soon as they began meeting started talking about things like intellectual graphics, cooperating processes, automation questions, email, and many other interesting possibilities 1 . In 1968, the group's task was to design NWG's first computer network, in October 1969, the first data exchange occurred and by the end of that year a network of four computers was in operation. Since the invention of the telephone in 1876 no other technology has revolutionized the field of communications over the computer network. The number of people who have made great contributions to the creation and development of the Internet are many, the computer network a much more complex than the phone is the result of people of many nationalities and cultures. However, remember that some years later in 19732 two computer scientists Robert Kahn and Vinton Cerft created a more sophisticated communication program called Transmission Control Protocol - Internet Protocol TCP / IP which is still in force in the Internet today.

NITROUS OXIDE EMISSIONS IN COVER CROP-BASED CORN PRODUCTION SYSTEMS

Nitrous oxide (N2O) is a potent greenhouse gas; the majority of N2O emissions are the result of agricultural management, particularly the application of N fertilizers to soils. The relationship of N2O emissions to varying sources of N (manures, mineral fertilizers, and cover crops) has not been well-evaluated. Here we discussed a novel methodology for estimating precipitation-induced pulses of N2O using flux measurements; results indicated that short-term intensive time-series sampling methods can adequately describe the magnitude of these pulses. We also evaluated the annual N2O emissions from corn-cover crop (Zea mays; cereal rye [Secale cereale], hairy vetch [Vicia villosa], or biculture) production systems when fertilized with multiple rates of subsurface banded poultry litter, as compared with tillage incorporation or mineral fertilizer. N2O emissions increased exponentially with total N rate; tillage decreased emissions following cover crops with legume components, while the effect of mineral fertilizer was mixed across cover crops.