Risk Assessment and Risk Management: Mending the Schism

The authors suggest that giving different individuals the responsibility for assessing and managing Risk may sometimes be counterproductive

Uued suunad GLP1 retseptori agonistide kasutamises diabeedi ravis

Väitekirja elektrooniline versioon ei sisalda publikatsiooneGlükagoonilaadne peptiid 1 (GLP1) on hormoon, mis vabaneb soolestikust vastusena söömisele. GLP1-l on erinevates elundsüsteemides mitmeid toimeid. See osaleb vere glükoositaseme regulatsioonis: stimuleerides insuliini ja inhibeerides glükagooni vabanemist veresuhkru tase langeb. GLP1 toimel aeglustub mao motoorika ja tühjenemine. Kesknärvisüsteemis reguleerib GLP1 söögiisu ning seeläbi kehakaalu. GLP1 füsioloogilistel toimetel põhineb ravimklassi GLP1 retseptori agonistide kasutamine. Need on laialdaselt kasutatavad diabeediravimid, mis lisaks veresuhkru taseme langetamisele vähendavad söögiisu ja alandavad kehakaalu. Ravimklass on võrdlemisi ohutu, kuna hüpoglükeemia risk on väike. Lisaks on kõrvaltoimed võrdlemisi kerged, sagedasemateks iiveldus ja oksendamine. GLP1 retseptori agonistide mõnede toimete suhtes kujuneb välja tolerantsus – näiteks mao motoorika aeglustumine väheneb ravimi kestval kasutusel. Samuti vähenevad ravimi korduval kasutamisel kõrvaltoimed, möödudes esimeste ravinädalatega. See, kas tolerantsus tekib ka GLP1 retseptori agonistide veresuhkru taset langetava toime suhtes, ei ole seni teada. GLP1 retseptori agoniste on kasutatud haruldaste ühe geeni rikkest põhjustatud suhkurtõve vormide puhul. Wolframi sündroom on geneetiline haigus, mille käigus arenevad 1. tüüpi diabeet, magediabeet ja silmanärvi kahjustus. Seni ei ole haigusel spetsiifilist ravi ja suhkruhaiguse tekkel kasutatakse tavaliselt insuliini süste. Käesolevas töös uurisime, kas GLP1 retseptori agoniste saaks kasutada Wolframi sündroomi puhul tekkiva suhkurtõve raviks. Uurimistöö eesmärkideks oli uurida GLP1 retseptori agonistide suhtes tekkivat tolerantsust hiirtel ja inimestel ning nende ravimite võimalikku toimet Wolframi sündroomi loommudelil. Eesmärkide saavutamiseks teostati loomkatseid hiirtel ning viidi läbi kliiniline uuring tervetel vabatahtlikel. Loomakatsete tulemused näitasid selget tolerantsuse teket hiirtel. Vastupidiselt loomkatsete tulemustele ei kujunenud aga tolerantsust välja inimeste puhul. Wolframi sündroomi loommudelis olid GLP1 retseptori agonistid efektiivsed veresuhkru langetajad, mis loob võimaluse nende kasutamiseks Wolframi sündroomi ravis.Glucagon-like peptide 1 (GLP1) is a peptide hormone secreted from the gastrointestinal tract in response to food ingestion. Moreover, GLP1 is secreted from the nervous system, where it functions as a neurotransmitter and, surprisingly, from the endocrine pancreas during metabolic stress. GLP1 regulates several biological functions in different organ systems. As one of the incretins, GLP1 stimulates in a glucose-dependent manner insulin secretion and inhibits that of glucagon, leading to a decrease in blood glucose levels. It decelerates gastric motility and emptying, regulates feeding behavior and body weight. GLP1 receptor agonists (GLP1RAs) have become a popular tool for treating type 2 diabetes, displaying positive impact beyond antihyperglycemic action. The key benefits of GLP1RAs include lower risk of hypoglycemia and modest weight loss. The adverse effects, most frequently nausea and vomiting, are generally mild and subside with time. One of the adverse effects of GLP1RA administration is decreased gastric motility. Interestingly, it is well known that this effect subsides with prolonged treatment. Thus, there is clear evidence that some effects of GLP1RAs are subject to tolerance development. It is logical to ask whether these drugs' core effects on glucose regulation may also be affected. GLP1RAs have been successfully used to treat certain forms of monogenic diabetes. We have asked whether a rare type of diabetes associated with Wolfram syndrome may respond to GLP1RAs. This study aimed to elucidate whether tolerance develops toward GLP1RAs’ glucose-lowering effects in mice and humans, and to investigate the drug class effect in the animal model of Wolfram syndrome. The results from our animal experiments demonstrated that the glucose lowering effect of GLP1RAs were clearly weaker after prolonged treatment. Unlike in mice, in the small clinical trial in healthy volunteers, the effects of GLP1RAs did not wane after 3 weeks of administration. Thus, tolerance toward GLP1RAs’ glucose lowering-effect developed in mice but not in humans. In the animal model of Wolfram syndrome, GLP1RAs potently decreased glucose levels and, therefore, may have potential in the treatment of patients with Wolfram syndrome.https://www.ester.ee/record=b546256

Põlevkiviõlitööstuse jäätmete tugevusomadused ja tsementeerumine

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Ida-Virumaa tasast pinnamoodi ilmestavad Kohtla-Järve ja Kiviõli külje all kõrguvad tehismäed, kuhu ladestatakse põlevkiviõlitööstuse jäätmeid. Need koosnevad õli tootmisel põlevkivist järele jäävast mineraalainest, kuid sisaldavad ka pisut orgaanikat, mis annab neile iseloomuliku musta värvuse. Sõltuvalt tootmistehnoloogiast tekib kahte tüüpi jäätmeid – jämedateralist poolkoksi ning peeneteralisemat musta tuhka. Mõlemad on keskkonnale ohtlikud, seetõttu on eriti olu¬line, et nad oleksid ladestatud viisil, mis tagab prügilate stabiilsuse ja keskkonnaohutuse. Seda kontrollivad peamiselt tugevus ja veejuhtivus, mis sõltuvad muuhulgas jäätmete mineraalsest koostisest ning selle muutumisest pärast ladestamist. Käesolevas doktoritöös uuriti õlitööstuse jäätmete mehaaniliste omaduste seoseid tsementeerumisega ja seda kontrollivate mineraalsete muutustega. Õli toomisel kuumutatakse põlevkivi kõrge temperatuurini, mille tõttu tekivad mitmed uusmineraalid. Nende hilisemal reageerimisel toimub tsementeerumine, mis seob algselt pudeda materjali tugevamaks massiiviks. Uuringute tulemused näitavad, et poolkoksiprügilaid moodustava materjali tugevus sõltub olulisel määral tsementeeriva mineraali ettringiidi moodustumisest. Ettringiit ei ole aga pikaajaliselt püsiv ning vanades poolkoksilasundites on kohati lisatugevust andev tsementatsioon hävinud. Seetõttu ei saa poolkoksi puhul pikaajalise lisatugevusega arvestada. Alternatiiviks võib olla poolkoksi ja põlevkivituha segamine ja koosladestamine. Katsete käigus selgus, et kui tuha hulk segus on suurem kui poolkoksi poorid mahutavad, praguneb segu intensiivse tsementeerumise tulemusena oluliselt. Pragude kaudu liiguks aga läbi ohtlike ja leonduvate jäätmete vesi, mis kannaks reostuse pinnasesse ja põhjavette. Seevastu kui tuhka on vähe, suurendab see poolkoksi tugevust ja lasundi stabiilsust. Uuemat õlitööstuse jääki musta tuhka pole seni eraldi ladestatud, kuid kasvavad mahud on tekitanud vajaduse sobiva ladestusmetoodika järele. Selle leidmiseks imiteeriti laborikatses mitmeid ladestamistehnoloogiaid. Selgus, et must tuhk tsementeerub veega kokku puutudes mitmeid kordi tugevamaks kui poolkoks ja seda põhjustavad mineraalid on võrreldes poolkoksiga keemiliselt stabiilsemad.Otherwise plain relief of Ida-Virumaa is contrasted by high artificial heaps near Kohtla-Järve and Kiviõli. These heaps accommodate huge amounts of shale-oil retorting wastes that are mainly composed of mineral matter remaining after processing of oil shale, but also contain leftover organic material that give the waste its dark color. Two types of waste are formed, which depend on the retorting technology – coarse-grained semi-coke and fine black ash. Both types are environmentally hazardous, thus they should be landfilled in a way that guarantees mechanical stability and environmental safety of landfills. These properties depend on strength and permeability that are controlled by mineral composition and alteration of the waste after disposal. The current thesis focuses on the relationship between mechanical properties, cementation and mineral alteration of oil shale retorting wastes. During retorting some minerals in found in oil shale decompose into unstable compounds. These compounds start to react and form new cementing phases that bind granular material together, thus contributing to its strength. The study shows that the strength properties of semi-coke highly depend on the formation of cementive mineral ettringite. Ettringite, however, is not stable in the long term and the cementation has occasionally disappeared in old semi-coke dumps. This suggests that semi-coke should be considered as granular material and the additional strength cannot be relied on. The alternative solution could be mixing and co-disposal of semi-coke and oil shale ash. If the ash content in the mixture exceeds the capacity of semi-coke pores, intensive formation of cementing minerals causes cracking. These cracks increase permeability and leached water can easily infiltrate into the surroundings. If the ash content stays low, the strength and stability of semi-coke is improved. Black ash, the new type of retorting waste, is not landfilled separately so far; however, the increasing volumes of this type of waste have raised the need for well-planned disposal method. Different methods were imitated in a laboratory experiment. It was found that black ash has good self-cementing properties and its strength exceeds that of semi-coke manyfold. Also the cementing phases in black ash are chemically more stable compared to semi-coke

Electronic Sentences: A systems development tool for young children

This poster describes Electronic Sentences (ES). This is a suite of software and hardware tools, along with supporting curriculum materials, that uses high-level electronic elements to allow young children to easily develop age-appropriate systems to solve real-world problems. As the name suggests, systems are created by assembling grammatically correct sentences that are scanned to create a corresponding electrical system. ES thus helps children develop literacy skills, logical thinking, design thinking and systems thinking. ES is designed to be used in conjunction with a wide range of modelling materials, which teachers will select with an eye to suitability for the children using the system. ES is being developed by a US/UK team. The target age for ES is anywhere between, in England, EYFS and Key Stage 1 and, in the US from grades pre-k-5. The design has focussed on useability for the youngest children in these ranges, i.e., children from 4 years on, while retaining attractiveness for older children, with the acknowledgement that teachers will use their judgement about when best to introduce ES. Limited trials of a prototype, fully working, system have taken place in US classrooms. This paper will, along with describing the ES system and its design aims, report on initial trials in English classrooms. It will explore the effectiveness of the system in achieving its multiple aims (the development of literacy skills, logical thinking, design thinking and systems thinking) and, in the light of these trials suggest necessary developments in the various elements of hardware, software and courseware that will be required before the product is made widely available

Majutusettevõtte veebipõhise müügi tõhustamine Antonius hotelli näitel

http://www.ester.ee/record=b4612123*es