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

Maternal effects on anogenital distance in a wild marmot population

Peer reviewedPublisher PD

Reduced haemodynamic response in the ageing visual cortex measured by absolute fNIRS

The effect of healthy ageing on visual cortical activation is still to be fully explored. This study aimed to elucidate whether the haemodynamic response (HDR) of the visual cortex altered as a result of ageing. Visually normal (healthy) participants were presented with a simple visual stimulus (reversing checkerboard). Full optometric screening was implemented to identify two age groups: younger adults (n = 12, mean age 21) and older adults (n = 13, mean age 71). Frequency-domain Multi-distance (FD-MD) functional Near-Infrared Spectroscopy (fNIRS) was used to measure absolute changes in oxygenated [HbO] and deoxygenated [HbR] haemoglobin concentrations in the occipital cortices. Utilising a slow event-related design, subjects viewed a full field reversing checkerboard with contrast and check size manipulations (15 and 30 minutes of arc, 50% and 100% contrast). Both groups showed the characteristic response of increased [HbO] and decreased [HbR] during stimulus presentation. However, older adults produced a more varied HDR and often had comparable levels of [HbO] and [HbR] during both stimulus presentation and baseline resting state. Younger adults had significantly greater concentrations of both [HbO] and [HbR] in every investigation regardless of the type of stimulus displayed (p<0.05). The average variance associated with this age-related effect for [HbO] was 88% and [HbR] 91%. Passive viewing of a visual stimulus, without any cognitive input, showed a marked age-related decline in the cortical HDR. Moreover, regardless of stimulus parameters such as check size, the HDR was characterised by age. In concurrence with present neuroimaging literature, we conclude that the visual HDR decreases as healthy ageing proceeds

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

Coordinated optimization of visual cortical maps (I) Symmetry-based analysis

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of OP columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about an hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference.Comment: 90 pages, 16 figure

Coverage, Continuity and Visual Cortical Architecture

The primary visual cortex of many mammals contains a continuous representation of visual space, with a roughly repetitive aperiodic map of orientation preferences superimposed. It was recently found that orientation preference maps (OPMs) obey statistical laws which are apparently invariant among species widely separated in eutherian evolution. Here, we examine whether one of the most prominent models for the optimization of cortical maps, the elastic net (EN) model, can reproduce this common design. The EN model generates representations which optimally trade of stimulus space coverage and map continuity. While this model has been used in numerous studies, no analytical results about the precise layout of the predicted OPMs have been obtained so far. We present a mathematical approach to analytically calculate the cortical representations predicted by the EN model for the joint mapping of stimulus position and orientation. We find that in all previously studied regimes, predicted OPM layouts are perfectly periodic. An unbiased search through the EN parameter space identifies a novel regime of aperiodic OPMs with pinwheel densities lower than found in experiments. In an extreme limit, aperiodic OPMs quantitatively resembling experimental observations emerge. Stabilization of these layouts results from strong nonlocal interactions rather than from a coverage-continuity-compromise. Our results demonstrate that optimization models for stimulus representations dominated by nonlocal suppressive interactions are in principle capable of correctly predicting the common OPM design. They question that visual cortical feature representations can be explained by a coverage-continuity-compromise.Comment: 100 pages, including an Appendix, 21 + 7 figure

The clinical and therapeutic uses of MDM2 and PSMA and their potential interaction in aggressive cancers

Prostate-specific membrane antigen (PSMA) overexpression is observed in the neovasculature of solid tumors, but not in the vasculature of normal tissues. Increased PSMA expression is positively associated with tumor stage and grade, although its function in cancer remains unclear. Mouse double minute 2 (MDM2) is a negative regulator of the p53 tumor suppressor and is reported to regulate VEGF expression and angiogenesis. Both proteins have been considered as biomarkers and therapeutic targets for advanced solid tumors. Our work and a recent microarray-based gene profiling study suggest there could be signaling interplay between MDM2 and PSMA. We herein review the mechanisms underlining the outgrowth of tumors associated with PSMA and MDM2, their potential interaction and how this may be applied to anticancer therapeutics

Mean ergodic composition operators on generalized Fock spaces

[EN] Every bounded composition operator C psi defined by an analytic symbol psi on the complex plane when acting on generalized Fock spaces F phi p,1 <= p <=infinity and p=0, is power bounded. Mean ergodic and uniformly mean ergodic bounded composition operators on these spaces are characterized in terms of the symbol. The behaviour for p=0 and p=infinity differs. The set of periodic points of these operators is also determined.The research of the first author is supported by ISP project, Addis Ababa University, Ethiopia. The research of the third author was partially supported by the research projects MTM2016-76647-P and GV Prometeo 2017/102 (Spain).Seyoum, W.; Mengestie, T.; Bonet Solves, JA. (2019). Mean ergodic composition operators on generalized Fock spaces. Revista de la Real Academia de Ciencias Exactas Físicas y Naturales Serie A Matemáticas. 114(1):1-11. https://doi.org/10.1007/s13398-019-00738-wS1111141Albanese, A.A., Bonet, J., Ricker, W.J.: Mean ergodic operators in Fréchet spaces. Anal. Acad. Sci. Fenn. Math. 34, 401–436 (2009)Beltrán-Meneu, M.J., Gómez-Collado, M.C., Jordá, E., Jornet, D.: Mean ergodic composition operators on Banach spaces of holomorphic functions. J. Funct. Anal. 270, 4369–4385 (2016)Bierstedt, K.D., Summers, W.H.: Biduals of weighted Banach spaces of analytic functions. J. Austr. Math. Soc. Ser. A 54, 70–79 (1993)Blasco, O.: Boundedness of Volterra operators on spaces of entire functions. Ann. Acad. Sci. Fenn. Math. 43, 89–107 (2018)Bonet, J., Domański, P.: A note on mean ergodic composition operators on spaces of holomorphic functions. Rev. R. Acad. Cienc. Exactas Fís. Nat. Ser. A Mat. RACSAM 105, 389–396 (2011)Bonet, J., Mangino, E.: Associated weights for spaces of $$p$$-integrable entire functions. Quaestiones Math. (2019). https://doi.org/10.2989/16073606.2019.1605420Bonet, J., Ricker, W.J.: Mean ergodicity of multiplication operators in weighted spaces of holomorphic functions. Arch. Math. 92, 428–437 (2009)Carswell, B.J., MacCluer, B.D., Schuster, A.: Composition operators on the Fock space. Acta Sci. Math. (Szeged) 69, 871–887 (2003)Constantin, O., Peláez, J.Á.: Integral operators, embedding theorems and a Littlewood-Paley formula on weighted Fock spaces. J. Geom. Anal. 26, 1109–1154 (2015)Cowen, C., MacCluer, B.: Composition Operators on Spaces of Analytic Functions. CRC Press, Boca Raton (1995)Dunford, N.: Spectral theory I convergence to projections. Trans. Am. Math. Soc. 54, 185–217 (1943)Guo, K., Izuchi, K.: Composition operators on Fock type space. Acta Sci. Math. (Szeged) 74, 807–828 (2008)Krengel, U.: Ergodic Theorems. Walter de Gruyter, Berlin (1985)Lotz, H.P.: Tauberian theorems for operators on $$L^1$$ and similar spaces. In: Bierstedt, K.D., Fuchssteiner, B. (eds.) Functional Analysis: Surveys and Recent Results III, pp. 117–133. North Holland, Amsterdam (1984)Lotz, H.P.: Uniform convergence of operators on $$L^{\infty }$$ and similar spaces. Math. Z. 190, 207–220 (1985)Lusky, W.: On the isomophism classes of weighted spaces of harmonic and holomorphic functions. Studia Math. 175, 19–45 (2006)Mengestie, T., Ueki, S.: Integral, differential and multiplication operators on weighted Fock spaces. Complex Anal. Oper. Theory. 13, 935–958 (2019)Mengestie, T., Seyoum, W.: Topological and dynamical properties of composition operators. Complex Anal. Oper. Theory (2018) (to appear)Mengestie, T., Seyoum, W.: Spectral properties of composition operators on Fock-Type spaces. Quaest. Math. (2019). https://doi.org/10.2989/16073606.2019.1692092Shapiro, J.H.: Composition Operators and Classical Function Theory. Springer, New York (1993)Wolf, E.: Power bounded composition operator. Comp. Method Funct. Theory 12, 105–117 (2012)Yosida, K.: Functional Analysis. Springer, Berlin (1978)Yosida, K., Kakutani, S.: Operator-theoretical treatment of Markoff’s Process and Mean Ergodic Theorem. Ann. Math. 42, 188–228 (1941

Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33–143 and 45–85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p &#60; 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of ‘core’ phenotypes

The impact of obesity on time spent with the provider and number of medications managed during office-based physician visits using a cross-sectional, national health survey

<p>Abstract</p> <p>Background</p> <p>Obesity is associated with morbidity, mortality, and increased health care costs. Few studies have examined the impact of obesity on outpatient office visits. The purpose of this study was to determine if outpatient visits by obese persons required more time with the provider and more prescription medication management compared to visits made by non-obese persons.</p> <p>Methods</p> <p>Obesity status was determined for 9,280 patient visits made by persons aged 18 years or older in the 2006 National Ambulatory Medical Care Survey. Multivariate analyses compared obese and non-obese visits, stratified by sex, for duration of the visit and the number of medications mentioned at the visit.</p> <p>Results</p> <p>Average duration of visit was higher among visits with patients determined to be obese. However, these differences were not considered significant after statistical testing. Visits made by obese female patients were significantly more likely to involve more than two prescription medications (OR 1.26, 95% CI 1.05 - 1.51) and visits made by obese male patients were significantly more likely to involve more than two prescription medications (OR 1.46, 95% CI 1.16 - 1.83) as compared to visits made by non-obese patients.</p> <p>Conclusion</p> <p>Time spent with the provider was found to be greater among visits with obese patients, but not significantly different from visits with non-obese patients. The number of medications for each visit was found to be significantly greater for visits where the patient was considered to be obese. Increased time for the visit and increased numbers of medication for each visit translate into increased costs. These findings document the impact of obesity on our health care system and have great implications on medical care cost and planning.</p