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Aminoglycoside (AG) antibiotics are widely used to prevent life-threatening infections, and cisplatin is used in the treatment of various cancers, but both are ototoxic and result in loss of sensory hair cells from the inner ear. ORC-13661 is a new drug that was derived from PROTO-1, a compound first identified as protective in a large-scale screen utilizing hair cells in the lateral line organs of zebrafish larvae. Here, we demonstrate, in zebrafish larvae and in mouse cochlear cultures, that ORC-13661 provides robust protection of hair cells against both ototoxins, the AGs and cisplatin. ORC-13661 also prevents both hearing loss in a dose-dependent manner in rats treated with amikacin and the loading of neomycin-Texas Red into lateral line hair cells. In addition, patch-clamp recordings in mouse cochlear cultures reveal that ORC-13661 is a high-affinity permeant blocker of the mechanoelectrical transducer (MET) channel in outer hair cells, suggesting that it may reduce the toxicity of AGs by directly competing for entry at the level of the MET channel and of cisplatin by a MET-dependent mechanism. ORC-13661 is therefore a promising and versatile protectant that reversibly blocks the hair cell MET channel and operates across multiple species and toxins., Candidate drug ORC-13661 robustly protects against ototoxicity by aminoglycoside antibiotics and cisplatin by reversibly blocking mechanotransduction of sensory hair cells.

Ämnet som denna studie behandlar är nyanländas integrering i det svenska samhället. Det framställs ett samhälleligt problem som teorier konkluderar är en följd av ett organisatoriskt problem bland de involverade parterna inom etableringsreformen. Syftet med denna uppsats är att studera hur de samverkande myndigheterna och kommunerna arbetar för att påverka nyanländas integrering och etablering i samhället, samt huruvida användningen av starkare styrmedel skulle påvisa sig bidra till en effektiv integrering av nyanlända. Två utvalda kommuner och samtliga myndigheter, förutom Migrationsverket, har intervjuats för att besvara på uppsatsens frågeställningar. Resultatet pekar på en god samverkan mellan parterna samtidigt som det även förekommer otydlighet kring ansvarsfördelning och arbetsuppgifter. Med tidigare erfarenheter som utgångspunkt kan det hävdas att det finns en stor sannolikhet att starkare styrmedel skulle kunna vara en effektiv åtgärd i att integrera nyanlända genom att förhindra att en stor andel nyanlända flyttar till segregerade områden där det inte råder goda förutsättningar för integration. The following study deals with the integration of new arrivals in Sweden. A societal problem is depicted which theories conclude is the result of an organizational problem among the partners in the establishment reform. The purpose of this essay is to study how the collaborating authorities and municipalities work together to influence the integration and establishment of new arrivals and also whether the use of more forceful means of actions would prove to contribute to an effective integration of newcomers. Two designated municipalities and all administrative authorities, with the exception of the Swedish Migration Agency, were interviewed to answer the essay questions. The results point towards a good cooperation between the parties; however, a lack of clarity of the partners' responsibilities and duties has been found. With previous experiences as a basis it can be argued that there is a high probability that the usage of more forceful means of actions could be an effective means of integrating newcomers by preventing large proportions from moving to segregated areas, where poor conditions for integration is prevalent. The study is written in Swedish.