Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics.

Low molecular weight opioid peptide esters (OPE) could become a class of analgesics with different side effect profiles than current opiates. OPE may have sufficient plasma stability to cross the blood brain barrier (BBB), undergo ester hydrolysis and produce analgesia. OPE of dipeptides, tyr-pro and tyr-gly conjugated to ethanol have a structure similar to the anesthestic agent, etomidate. Based upon the analgesic activity of dipeptide opioids, Lipinski's criteria, and permeability of select GABA esters to cross the BBB, opioid peptides (OP) conjugated to ethanol, cholesterol or 3-glucose are lead recommendations. Preliminary animal data suggests that tyr-pro-ethyl ester crosses the BBB and unexpectedly produces hyperalgesia. Currently, there are no approved OP analgesics available for clinical use. Clinical trials of good manufacturing practice OP administered to patients suffering from chronic pain with indwelling intrathecal pumps could resolve the issue that OP may be superior to opiates and may redirect research.

Evaluating the Feasibility of Implementing a Green Roof Retrofit on Pitched Residential Roofs

Green roofs are one solution to stormwater runoff which is a major environmental problem. However, the majority of green roofs are primarily implemented on flat roofed commercial buildings and not residential homes with sloped roofs. Team SO GREEN designed a light-weight green roof system retrofit for residential homes. Between June and November 2014, green roof performance data was collected and compared between the designed sloped roofs and a non-sloped control. The sloped design performed well and one test slope was improved with a recirculating irrigation system. An economic analysis was made and a focus group determined preliminary consumer interest, aesthetic preferences, and barriers. This study enriches the body of knowledge regarding bringing green roof systems to the residential home market.

Quality of care for cancer patients on home parenteral nutrition: Development of key interventions and outcome indicators using a two-round Delphi approach

Purpose: Clear recommendations on how to guide patients with cancer on home parenteral nutrition (HPN) are lacking as the use of HPN in this population remains a controversial issue. Therefore, the aims of this study were to rank treatment recommendations and main outcome indicators to ensure high-quality care and to indicate differences in care concerning benign versus malignant patients. Methods: Treatment recommendations, identified from published guidelines, were used as a starting point for a two-round Delphi approach. Comments and additional interventions proposed in the first round were reevaluated in the second round. Ordinal logistic regression with SPSS 2.0 was used to identify differences in care concerning benign versus malignant patients. Results: Twenty-seven experts from five European countries completed two Delphi rounds. After the second Delphi round, the top three most important outcome indicators were (1) quality of life (QoL), (2) incidence of hospital readmission and (3) incidence of catheter-related infections. Forty-two interventions were considered as important for quality of care (28/42 based on published guidelines; 14/42 newly suggested by Delphi panel). The topics 'Liver disease' and 'Metabolic bone disease' were considered less important for cancer patients, together with use of infusion pumps (p = 0.004) and monitoring of vitamins and trace elements (p = 0.000). Monitoring of QoL is considered more important for cancer patients (p = 0.03). Conclusion: Using a two-round Delphi approach, we developed a minimal set of 42 interventions that may be used to determine quality of care in HPN patients with malignancies. This set of interventions differs from a similar set developed for benign patients. © 2012 Springer-Verlag Berlin Heidelberg.

Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain

P-glycoprotein (P-gp) is one of the best-known mediators of drug efflux-based multidrug resistance in many cancers. This validated therapeutic target is a prototypic, plasma membrane resident ATPBinding Cassette transporter that pumps xenobiotic compounds out of cells. The large, polyspecific drug-binding pocket of P-gp recognizes a variety of structurally unrelated compounds. The transport of these drugs across the membrane is coincident with changes in the size and shape of this pocket during the course of the transport cycle. Here, we present the crystal structures of three inward-facing conformations of mouse P-gp derived from two different crystal forms. One structure has a nanobody bound to the C-terminal side of the first nucleotide-binding domain. This nanobody strongly inhibits the ATP hydrolysis activity of mouse Pgp by hindering the formation of a dimeric complex between the ATP-binding domains, which is essential for nucleotide hydrolysis. Together, these inward-facing conformational snapshots of P-gp demonstrate a range of flexibility exhibited by this transporter, which is likely an essential feature for the binding and transport of large, diverse substrates. The nanobody-bound structure also reveals a unique epitope on P-gp.

Valoración económica productiva de tres sistemas de riego localizado en naranjo (Citrus sinensis L.)

p.33-39

El riego por goteo como sistema para la aplicación de agentes biocontroladores de fitopatógenos del suelo

p.31-35

El valor del agua a partir del mercado regional : el caso de la producción de arroz con riego en el litoral argentino

p.239-249

Resistencia y resiliencia a la degradación salina y sódica de suelos pampeanos, disturbados por riego complementario

p.119-130

Variaciones del contenido de NO(-3) y NH(+4) en suelos : producidas por aplicación de diversas láminas de riego

p.19-27

Computational magnetohydrodynamics - Application

There are many processes, particularly in the nuclear and metals processing industries, where electromagnetic fields are used to influence the flow behaviour of a fluid. Procedures exploiting finite volume (FV) methods in both structured and unstructured meshes have recently been developed which enable this influence to be modelled in the context of conventional FV CFD codes. A range of problems have been tackled by the authors, including electromagnetic pumps and brakes, weirs and dams in steelmaking tundishes and interface effects in aluminium smelting cells. Two cases are presented here, which exemplify the application of the new procedures. The first case investigates the influence of electromagnetic fields on solidification front progression in a tin casting and the second case shows how the liquid metals free surface may be controlled through an externally imposed magnetic field in the semi-levitation casting process.

Supporting breastfeeding mothers on children’s wards: an overview

Just under half of all six-week-old babies in the UK are breastfed, and just under a quarter are still being breastfed at six months old so it is likely that children’s nurses will frequently encounter breastfed babies on children’s wards. Support for breastfeeding has traditionally been left to midwives but Department of Health guidance requires that all relevant staff have training in this practice. Children’s nurses need to understand the principles and practice of breastfeeding support including correct positioning and attachment, prevention and management of breastfeeding problems, mothers’ needs and safe use of breast pumps. Breastfeeding should be part of the curriculum for children’s nursing courses, including practical sessions to observe breastfeeding support in the clinical setting. Children’s nurses should be aware that literature and learning resources written for midwives might be appropriate for them to access to increase their understanding in this important area of practice.

Impacts of the Oceans on Climate Change

The oceans play a key role in climate regulation especially in part buffering (neutralising) the effects of increasing levels of greenhouse gases in the atmosphere and rising global temperatures. This chapter examines how the regulatory processes performed by the oceans alter as a response to climate change and assesses the extent to which positive feedbacks from the ocean may exacerbate climate change. There is clear evidence for rapid change in the oceans. As the main heat store for the world there has been an accelerating change in sea temperatures over the last few decades, which has contributed to rising sea‐level. The oceans are also the main store of carbon dioxide (CO2), and are estimated to have taken up ∼40% of anthropogenic-sourced CO2 from the atmosphere since the beginning of the industrial revolution. A proportion of the carbon uptake is exported via the four ocean ‘carbon pumps��� (Solubility, Biological, Continental Shelf and Carbonate Counter) to the deep ocean reservoir. Increases in sea temperature and changing planktonic systems and ocean currents may lead to a reduction in the uptake of CO2 by the ocean; some evidence suggests a suppression of parts of the marine carbon sink is already underway. While the oceans have buffered climate change through the uptake of CO2 produced by fossil fuel burning this has already had an impact on ocean chemistry through ocean acidification and will continue to do so. Feedbacks to climate change from acidification may result from expected impacts on marine organisms (especially corals and calcareous plankton), ecosystems and biogeochemical cycles. The polar regions of the world are showing the most rapid responses to climate change. As a result of a strong ice–ocean influence, small changes in temperature, salinity and ice cover may trigger large and sudden changes in regional climate with potential downstream feedbacks to the climate of the rest of the world. A warming Arctic Ocean may lead to further releases of the potent greenhouse gas methane from hydrates and permafrost. The Southern Ocean plays a critical role in driving, modifying and regulating global climate change via the carbon cycle and through its impact on adjacent Antarctica. The Antarctic Peninsula has shown some of the most rapid rises in atmospheric and oceanic temperature in the world, with an associated retreat of the majority of glaciers. Parts of the West Antarctic ice sheet are deflating rapidly, very likely due to a change in the flux of oceanic heat to the undersides of the floating ice shelves. The final section on modelling feedbacks from the ocean to climate change identifies limitations and priorities for model development and associated observations. Considering the importance of the oceans to climate change and our limited understanding of climate-related ocean processes, our ability to measure the changes that are taking place are conspicuously inadequate. The chapter highlights the need for a comprehensive, adequately funded and globally extensive ocean observing system to be implemented and sustained as a high priority. Unless feedbacks from the oceans to climate change are adequately included in climate change models, it is possible that the mitigation actions needed to stabilise CO2 and limit temperature rise over the next century will be underestimated.

Response of a floodplain fish community to river-floodplain connectivity: natural versus managed reconnection

To restore lateral connectivity in highly regulated river-floodplain systems, it has become necessary to implement localized, "managed" connection flows, made possible using floodplain irrigation infrastructure. These managed flows contrast with "natural", large-scale, overbank flood pulses. We compared the effects of a managed and a natural connection event on (i) the composition of the large-bodied fish community and (ii) the structure of an endangered catfish population of a large floodplain lake. The change in community composition following the managed connection was not greater than that exhibited between seasons or years during disconnection. By contrast, the change in fish community structure following the natural connection was much larger than that attributed to background, within-and between-year variability during disconnection. Catfish population structure only changed significantly following the natural flood. While the natural flood increased various population rates of native fishes, it also increased those of non-native carp, a pest species. To have a positive influence on native biodiversity, environmental flows may need to be delivered to floodplains in a way that simulates the properties of natural flood pulses. A challenge, however, will be managing river-floodplain connectivity to benefit native more than non-native species.

Introduction to the BASIN Special Issue: State of art, past present a view to the future

Marine ecosystems are complex networks of organisms interacting either directly or indirectly while under the influence of the physical and chemical properties of the medium they inhabit. The interplay between these biological agents and their abiotic environment results in complex non-linear responses to individual and multiple stressors, influenced by feedbacks between these organisms and their environment. These ecosystems provide key services that benefit humanity such as food provisioning via the transfer of energy to exploited fish populations or climate regulation via the sinking, subsequent mineralization and ultimately storage of carbon in the ocean interior. These key characteristics or emergent features of marine ecosystems are subject to rapid change (e.g. regime shifts; Alheit et al., 2005 and Scheffer et al., 2009), with outcomes that are largely unpredictable in a deterministic sense. The North Atlantic Ocean is host to a number of such systems which are collectively being influenced by the unique physical and chemical features of this ocean basin, such as the Atlantic Meridional Overturning Circulation (AMOC), the basin’s ventilation with the Arctic Ocean, the dynamics of heat transport via the Gulf Stream and the formation of deep water at high latitudes. These features drive the solubility and biological pumps and support the production and environments that results in large exploited fish stocks. Our knowledge of its functioning as a coupled system, and in particular how it will respond to change, is still limited despite the scientific effort exerted over more than 100 years. This is due in part to the difficulty of providing synoptic overviews of a vast area, and to the fact that most fieldwork provides only snapshots of the complex physical, chemical and biological processes and their interactions. These constraints have in the past limited the development of a mechanistic understanding of the basin as a whole, and thus of the services it provides.

Hydrochemical and isotopic tracing of mixing dynamics and water quality evolution under pumping conditions in the mine shaft of the abandoned Frances Colliery, Scotland.

Since 1995, when pumps were withdrawn from deep mines in East Fife (Scotland), mine waters have been rebounding throughout the coalfield. Recently, it has become necessary to pump and treat these waters to prevent their uncontrolled emergence at the surface. However, even relatively shallow pumping to surface treatment lagoons of the initially chemically-stratified mine water from a shaft in the coastal Frances Colliery during two dynamic step-drawdown tests to establish the hydraulic characteristics of the system resulted in rapid breakdown of the stratification within 24 h and a poor pumped water quality with high dissolved Fe loading. Further, data are presented here of hydrochemical and isotopic sampling of the extended pump testing lasting up to several weeks. The use in particular of the environmental isotopes d18O, d2H, d34S, 3H, 13C and 14C alongside hydrochemical and hydraulic pump test data allowed characterisation of the Frances system dynamics, mixing patterns and water quality sources feeding into this mineshaft under continuously pumped conditions. The pumped water quality reflects three significant components of mixing: shallow freshwater, seawater, and leakage from the surface treatment lagoons. In spite of the early impact of recirculating lagoon waters on the hydrochemistries, the highest Fe loadings in the longer-term pumped waters are identified with a mixed freshwater–seawater component affected by pyrite oxidation/melanterite dissolution in the subsurface system.