Use of models for the environmental risk assessment of veterinary medicines in European aquaculture: current situation and future perspectives

Veterinary Medicinal Products (VMPs) are used in intensive aquaculture production to treat a wide range of bacterial and parasitic infestations. Their release into the environment poses concerns regarding their potential ecotoxicological risks to aquatic ecosystems, which need to be evaluated making use of appropriate Environmental Risk Assessment (ERA) schemes and models. This study presents an overview of the major aquaculture production systems in Europe, the VMPs most commonly used, and the environmental quality standards and regulatory procedures available for their ERA. Furthermore, it describes the state-of-the-art on the development of environmental models capable of assessing the fate, exposure, ecotoxicological effects and risks of VMPs in aquaculture production systems, and discusses their level of development and implementation within European aquaculture. This study shows that the use of environmental models in regulatory ERA is somewhat limited in many European countries. Major efforts have been dedicated to assess the fate and exposure of antiparasitic compounds in salmonid cage systems, particularly in Scotland, while models and scenarios for assessing dispersal of antimicrobials, in general, and antiparasitic compounds in the Mediterranean as well as in Scandinavian regions are less available. On the other hand, the use of ecological models for assessing the effects and risks of VMPs is almost absent. Recommendations are provided to improve the chemical exposure and effect assessments and the ecological realism of the modelling outcomes, paying special attention to the protection goals set for the regulatory ERA of VMPs in Europ

How and When Socially Entrepreneurial Nonprofit Organizations Benefit From Adopting Social Alliance Management Routines to Manage Social Alliances?

Social alliance is defined as the collaboration between for-profit and nonprofit organizations. Building on the insights derived from the resource-based theory, we develop a conceptual framework to explain how socially entrepreneurial nonprofit organizations (SENPOs) can improve their social alliance performance by adopting strategic alliance management routines. We test our framework using the data collected from 203 UK-based SENPOs in the context of cause-related marketing campaign-derived social alliances. Our results confirm a positive relationship between social alliance management routines and social alliance performance. We also find that relational mechanisms, such as mutual trust, relational embeddedness, and relational commitment, mediate the relationship between social alliance management routines and social alliance performance. Moreover, our findings suggest that different types of social alliance motivation can influence the impact of social alliance management routines on different types of the relational mechanisms. In general, we demonstrate that SENPOs can benefit from adopting social alliance management routines and, in addition, highlight how and when the social alliance management routines–social alliance performance relationship might be shaped. Our study offers important academic and managerial implications, and points out future research directions

Cosmic rays and molecular clouds

This paper deals with the cosmic-ray penetration into molecular clouds and with the related gamma--ray emission. High energy cosmic rays interact with the dense gas and produce neutral pions which in turn decay into two gamma rays. This makes molecular clouds potential sources of gamma rays, especially if they are located in the vicinity of a powerful accelerator that injects cosmic rays in the interstellar medium. The amplitude and duration in time of the cosmic--ray overdensity around a given source depend on how quickly cosmic rays diffuse in the turbulent galactic magnetic field. For these reasons, gamma-ray observations of molecular clouds can be used both to locate the sources of cosmic rays and to constrain the properties of cosmic-ray diffusion in the Galaxy.Comment: To appear in the proceedings of the San Cugat Forum on Astrophysics 2012, 27 pages, 10 figure

UK-68,798, A Class III Antiarrhythmic Drug with Antifibrillatory Properties

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74787/1/j.1527-3466.1992.tb00244.x.pd

The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer

Many kallikrein genes were found to be differentially expressed in various malignancies, and prostate specific antigen (encoded by the KLK3 gene) is the best tumour marker for prostate cancer. Prostate specific antigen has recently been shown to be an independent favourable prognostic marker for breast cancer. KLK15 is newly discovered kallikrein gene that is located adjacent to KLK3 on chromosome 19q13.4. KLK15 has 41% similarity to KLK3 and the encoded protein, hK15, can activate pro-prostate specific antigen. We studied the expression of KLK15 by real-time quantitative reverse transcriptase–polymerase chain reaction in 202 tissues from patients with breast carcinoma of various stages, grades and histological types. KLK15 expression was found to be a significant predictor of progression-free survival (hazard ratio of 0.41 and P=0.011) and overall survival (hazard ratio of 0.34 and P=0.009). When all other known confounders were controlled in the multivariate analysis, KLK15 retained its prognostic significance. Higher concentrations of KLK15 mRNA were found more frequently in node negative patients (P=0.042). No association was found between KLK15 expression and any other clinicopathological variable. Further, KLK15 is an independent prognostic factor of progression-free survival and overall survival in the subgroup of patients with lower grade and those with oestrogen receptor and progesterone receptor negative tumours in both univariate and multivariate analysis. KLK15 levels of expression were slightly higher (although not statistically significant) in the oestrogen receptor negative and progesterone receptor negative subgroups of patients. KLK15 is up-regulated by androgens in breast cancer cell lines. Time-course and blocking experiments suggest that this regulation is mediated through the androgen receptor

Role of endogenous and exogenous female sex hormones in arthritis and osteoporosis development in B10.Q-ncf1*/* mice with collagen-induced chronic arthritis

<p>Abstract</p> <p>Background</p> <p>Collagen-induced arthritis (CIA) is an often-used murine model for human rheumatoid arthritis (RA). Earlier studies have shown potent anti-arthritic effects with the female sex hormone estradiol and the selective estrogen receptor modulator (SERM) raloxifene in CIA in DBA/1-mice. B10.Q-ncf1^*/*mice are B10.Q mice with a mutated Ncf1 gene. In B10.Q-ncf1^*/*mice, CIA develops as a chronic relapsing disease, which more accurately mimics human RA. We investigated the role of endogenous and exogenous sex steroids and raloxifene in the course of this model of chronic arthritis. We also examined whether treatment would prevent the development of inflammation-triggered generalized osteoporosis.</p> <p>Methods</p> <p>Female B10.Q-ncf1^*/*mice were sham-operated or ovariectomized, and CIA was induced. 22 days later, when 30% of the mice had developed arthritis, treatment with raloxifene, estradiol or vehicle was started, and the clinical disease was evaluated continuously. Treatment was continued until day 56 after immunization. At termination of the experiment (day 73), bone mineral density (BMD) was analyzed, paws were collected for histological examination, and sera were analyzed for markers of cartilage turnover and pro-inflammatory cytokines.</p> <p>Results</p> <p>Raloxifene and estradiol treatment, as well as endogenous estrogen, decreased the frequency of arthritis, prevented joint destruction and countered generalized osteoporosis. These effects were associated with lower serum levels of the pro-inflammatory cytokine IL-6.</p> <p>Conclusions</p> <p>This is the first study to show that raloxifene and estradiol can ameliorate established erosive arthritis and inflammation-triggered osteoporosis in this chronic arthritis model. We propose that treatment with raloxifene could be a beneficial addition to the treatment of postmenopausal RA.</p

Minimum pricing of alcohol versus volumetric taxation:which policy will reduce heavy consumption without adversely affecting light and moderate consumers?

Background We estimate the effect on light, moderate and heavy consumers of alcohol from implementing a minimum unit price for alcohol (MUP) compared with a uniform volumetric tax. Methods We analyse scanner data from a panel survey of demographically representative households (n = 885) collected over a one-year period (24 Jan 2010–22 Jan 2011) in the state of Victoria, Australia, which includes detailed records of each household's off-trade alcohol purchasing. Findings The heaviest consumers (3% of the sample) currently purchase 20% of the total litres of alcohol (LALs), are more likely to purchase cask wine and full strength beer, and pay significantly less on average per standard drink compared to the lightest consumers (A$1.31 [95$2.21 [95% CI 2.10–2.31]). Applying a MUP of A$1 per standard drink has a greater effect on reducing the mean annual volume of alcohol purchased by the heaviest consumers of wine (15.78 LALs [95$393.60 [95% CI 374.19–413.00]) and beer ($108.26 [95$552.46 [95% CI 530.55–574.36] and $163.92 [95% CI 152.79–175.03], respectively). Both a MUP and uniform volumetric tax have little effect on changing the annual cost of wine and beer for light and moderate consumers, and likewise little effect upon their purchasing. Conclusions While both a MUP and a uniform volumetric tax have potential to reduce heavy consumption of wine and beer without adversely affecting light and moderate consumers, a MUP offers the potential to achieve greater reductions in heavy consumption at a lower overall annual cost to consumers

Prevention of type 2 diabetes in adults with impaired glucose tolerance: the European Diabetes Prevention RCT in Newcastle upon Tyne, UK

<p>Abstract</p> <p>Background</p> <p>Diabetes prevalence is increasing. The Finnish Diabetes Prevention Study (DPS) showed a 58% reduction in Type 2 Diabetes (T2D) incidence in adults with impaired glucose tolerance (IGT). The European Diabetes Prevention Study (EDIPS) extends the DPS to different European populations, using the same study design. In the Newcastle arm of this study (EDIPS-Newcastle), we tested the hypothesis that T2D can be prevented by lifestyle intervention and explored secondary outcomes in relation to diabetes incidence.</p> <p>Methods</p> <p>We recruited 102 participants (42 men and 60 women, mean age 57 years, mean BMI 34 kgm^-2) with IGT to EDIPS-Newcastle and randomised to Intervention and usual care Control groups. The intervention included individual motivational interviewing aimed at: weight reduction, increase in physical activity, fibre and carbohydrate intake and reduction of fat intake (secondary outcomes). The primary outcome was diagnosis of T2D.</p> <p>Results</p> <p>Mean duration of follow-up was 3.1 years. T2D was diagnosed in 16 participants (I = 5, C = 11). Absolute incidence of T2D was 32.7 per 1000 person-years in the Intervention-group and 67.1 per 1000 person-years in the Control-group. The overall incidence of diabetes was reduced by 55% in the Intervention-group, compared with the Control-group: RR 0.45 (95%CI 0.2 to 1.2).</p> <p>Explanatory survival analysis of secondary outcomes showed that those who sustained beneficial changes for two or more years reduced their risk of developing T2D.</p> <p>Conclusion</p> <p>Our results are consistent with other diabetes prevention trials. This study was designed as part of a larger study and although the sample size limits statistical significance, the results contribute to the evidence that T2D can be prevented by lifestyle changes in adults with IGT. In explanatory analysis small sustained beneficial changes in weight, physical activity or dietary factors were associated with reduction in T2D incidence.</p> <p>Trial Registration</p> <p>International Standard Randomised Controlled Trial Number registry (ISRCTN)</p> <p>Registry number: ISRCTN 15670600</p> <p><url>http://www.controlled-trials.com/isrctn/search.html?srch=15670600&sort=3&dir=desc&max=10</url></p

Gold nanocrystals with variable index facets as highly effective cathode catalysts for lithium-oxygen batteries

© 2015 Nature Publishing Group All rights reserved. Cathode catalysts are the key factor in improving the electrochemical performance of lithium-oxygen (Li-O2) batteries via their promotion of the oxygen reduction and oxygen evolution reactions (ORR and OER). Generally, the catalytic performance of nanocrystals (NCs) toward ORR and OER depends on both composition and shape. Herein, we report the synthesis of polyhedral Au NCs enclosed by a variety of index facets: cubic gold (Au) NCs enclosed by {100} facets; truncated octahedral Au NCs enclosed by {100} and {110} facets; and trisoctahedral (TOH) Au NCs enclosed by 24 high-index {441} facets, as effective cathode catalysts for Li-O2 batteries. All Au NCs can significantly reduce the charge potential and have high reversible capacities. In particular, TOH Au NC catalysts demonstrated the lowest charge-discharge overpotential and the highest capacity of ∼ 20 298 mA h g-1. The correlation between the different Au NC crystal planes and their electrochemical catalytic performances was revealed: high-index facets exhibit much higher catalytic activity than the low-index planes, as the high-index planes have a high surface energy because of their large density of atomic steps, ledges and kinks, which can provide a high density of reactive sites for catalytic reactions