Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80–85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery

Multiple Parton Interactions in Z+jets production at the LHC. A comparison of factorized and non--factorized double parton distribution functions

We examine the contribution of Multiple Parton Interactions to Z+n-jets production at the LHC, n=2,3,4, where the Z boson is assumed to decay leptonically. We compare the results obtained with the correlated GS09 double parton distribution function with those obtained with two instances of fully factorized single parton distribution functions: MSTW2008LO and CTEQ6LO. It appears quite feasible to measure the MPI contribution to Z+2/3/4 jets already in the first phase of the LHC with a total luminosity of one inverse femtobarn at 7 TeV. If as expected the trigger threshold for single photons is around 80 GeV, Z+2-jets production may well turn out to be more easily observable than the gamma+3-jets channel. The MPI cross section is dominated by relatively soft events with two jets balancing in transverse momentum.Comment: 15 pages, 3 plot

Geometric properties and continuity of the pre-duality mapping in Banach space

We use the preduality mapping in proving characterizations of some geometric properties of Banach spaces. In particular, those include nearly strongly convexity, nearly uniform convexity-a property introduced by K. Goebel and T. Sekowski-, and nearly very convexity.We thank a referee for the careful reading of the manuscript. His/her observations substantially improved the overall aspect of the present work, detected several misprints and made some convenient changes. This work was supported by: (1) The National Natural Science Foundation of China (Grant no. 11271248). (2) Specific Academic Discipline Project of Shanghai Municipal Education Commission (Grant no. B-8932-13-0136). (3) Project MTM2011-22417, Ministerio de Ciencia e Innovacion, Spain (V. Montesinos).Zhang, ZH.; Montesinos Santalucia, V.; Liu, CY.; Gong, WZ. (2015). Geometric properties and continuity of the pre-duality mapping in Banach space. Revista de la Real Academia de Ciencias Exactas, Fisicas y Naturales. Serie A. Matematicas. 109(2):407-416. https://doi.org/10.1007/s13398-014-0190-6S4074161092Bandyopadhyay, P., Huang, D., Lin, B.L., Troyanski, S.L.: Some generalizations of local uniform rotundity. J. Math. Anal. Appl. 252, 906–916 (2000)Bandyopadhyay, P., Li, Y., Lin, B., Narayana, D.: Proximinality in Banach spaces. J. Math. Anal. Appl. 341, 309–317 (2008)Diestel, J.: Geometry of Banach Spaces. Selected Topics, LNM, vol. 485. Springer, Berlin (1975)Fabian, M., Habala, P., Hájek, P., Montesinos, V., Zizler, V.: Banach Space Theory. The Basis for Linear and Nonlinear Analysis, CMS Books in Mathematics. Springer, Berlin (2011)Giles, J.R., Gregory, D.A., Sims, B.: Geometrical implications of upper semi-continuity of the duality mapping on a Banach space. Pacific J. Math. 79(1), 99–109 (1978)Goebel, K., Sekowski, T.: The modulus of non-compact convexity. Ann. Univ. M. Curie-Sklodowska, Sect. A 38, 41–48 (1984)Guirao, A.J., Montesinos, V.: A note in approximative compactness and continuity of metric projections in Banach spaces. J. Convex Anal. 18, 397–401 (2011)Huff, R.: Banach spaces which are nearly uniformly convex. Rocky Mountain J. Math. 10(4), 743–749 (1980)Kutzarova, D., Rolewicz, S.: On nearly uniformly convex sets. Arch. Math. 57, 385–394 (1991)Kutzarova, D., Lin, B.L., Zhang, W.: Some geometrical properties of Banach spaces related to nearly uniform convexity. Contemp. Math. 144, 165–171 (1993)Kutzarova, D., Prus, S.: Operators which factor through nearly uniformly convex spaces. Boll. Un. Mat. Ital. B (7) 9, 2, 479–494 (1995)Montesinos, V.: Drop property equals reflexivity. Studia Math. 87, 93–100 (1987)Phelps, R.R.: Convex Functions, Monotone Operators and Differentiability, LNM, vol. 1364, 2nd edn. Springer, Berlin (1993)Rolewicz, S.: On drop property. Studia Math. 85, 27–37 (1986)Rolewicz, S.: On $$\Delta$$ Δ -uniform convexity and drop property. Studia Math. 87, 181–191 (1987)Wu, C.X., Li, Y.J.: Strong convexity in Banach spaces. J. Math. Wuhan Univ. 13(1), 105–108 (1993)Wang, J.H., Nan, C.X.: The continuity of subdifferential mapping. J. Math. Anal. Appl. 210, 206–214 (1997)Wang, J.H., Zhang, Z.H.: Characterization of the property (C-K). Acta Math. Sci. Ser. A Chin. Ed. 17(A)(3), 280–284 (1997)Zhang, Z.H., Liu, C.Y.: Some generalization of locally and weakly locally uniformly convex space. Nonlinear Anal. 74(12), 3896–3902 (2011)Zhang, Z.H., Liu, C.Y.: Convexity and proximinality in Banach spaces. J. Funct. Spaces Appl. 2012, 11 (2012). doi: 10.1155/2012/724120 . Article ID 724120Zhang, Z.H., Liu, C.Y.: Convexity and existence of the farthest point. Abstract Appl. Anal. 2011, 9 (2011). doi: 10.1155/2011/139597 . Article ID 139597Zhang, Z.H., Shi, Z.R.: Convexities and approximative compactness and continuity of the metric projection in Banach spaces. J. Approx. Theory 161(2), 802–812 (2009)Zhang, Z.H., Zhang, C.J.: On very rotund Banach spaces. Appl. Math. Mech. (English Ed.) 21(8), 965–970 (2000

Innovation in citizen science – perspectives on science-policy advances

Citizen science is growing as a field of research with contributions from diverse disciplines, promoting innovation in science, society, and policy. Inter- and transdisciplinary discussions and critical analyses are needed to use the current momentum to evaluate, demonstrate, and build on the advances that have been made in the past few years. This paper synthesizes results of discussions at the first international citizen science conference of the European Citizen Science Association (ECSA) in 2016 in Berlin, Germany, and distills major points of the discourse into key recommendations. To enhance innovation in science, citizen science needs to clearly demonstrate its scientific benefit, branch out across disciplines, and foster active networking and new formats of collaboration, including true co-design with participants. For fostering policy advances, it is important to embrace opportunities for policy-relevant monitoring and policy development and to work with science funders to find adequate avenues and evaluation tools to support citizen science. From a society angle it is crucial to engage with societal actors in various formats that suit participants and to evaluate two-way learning outcomes as well as to develop the transformative role of science communication. We hope that these key perspectives will promote citizen science progress at the science-society-policy interface

Inferior vestibular neuritis: 3 cases with clinical features of acute vestibular neuritis, normal calorics but indications of saccular failure

BACKGROUND: Vestibular neuritis (VN) is commonly diagnosed by demonstration of unilateral vestibular failure, as unilateral loss of caloric response. As this test reflects the function of the superior part of the vestibular nerve only, cases of pure inferior nerve neuritis will be lost. CASE PRESENTATIONS: We describe three patients with symptoms suggestive of VN, but normal calorics. All 3 had unilateral loss of vestibular evoked myogenic potential. A slight, asymptomatic position dependent nystagmus, with the pathological ear down, was observed. CONCLUSION: We believe that these patients suffer from pure inferior nerve vestibular neuritis