The usage and replacement principles of roadblocks

Diplomityö käsittelee ajoesteiden käyttötapoja osana kuntien katuverkon rakennetta. Työn tavoitteena on ollut löytää keinoja ajoesteiden tarpeen vähentämiselle. Tutkimuskaupunkeina toimivat Lahti ja Vantaa, joiden ajoestekäytäntöjen pohjalta tarkasteltiin toteutuneita ratkaisuja ja vallitsevia ympäristötekijöitä paikkatietoaineistojen ja kaupunkien sisäisten työpajojen kautta. Kirjallisuuskatsauksessa tarkasteltiin katuverkon rakennetta ja katutilaan vaikuttavia tekijöitä sekä liikenneympäristön rakentumista ja kehittymistä eri kaupunkisuunnittelun ajanjaksoina. Tavoitteena oli kartoittaa, miten eri aikakausien suunnitteluperiaatteet ovat vaikuttaneet katuverkon muodostumiseen, ja miten hyvin ratkaisut palvelevat liikenteen käyttäjiä nykyään. Lisäksi kartoitettiin ajoesteiden tyyppejä, lainsäädännöllistä perustaa sekä ajoesteiden käyttöä muutamien kansainvälisten esimerkkien kautta. Tapaustutkimuksessa analysoitiin tutkimuskaupunkien koostamia ajoesteaineistoja estetyypin, katuverkon roolin ja lähiympäristön ominaisuuksien perusteella. Tarkastelussa löytyi selviä luokkia, joissa ajoesteiden käyttöön oli toistuvasti jouduttu turvautumaan. Laadullisessa tarkastelussa nousi esiin, että valtaosassa ajoestekohteissa ympäristön laatu oli viimeistelemätöntä, eikä esimerkiksi liikennejärjestelyjen muutoksia oltu liikennemerkkien ja mahdollisten esteiden asentamisen lisäksi juuri toteutettu. Tässä työssä pyrittiin muodostamaan periaatteellisen tason ratkaisuja ja ohjeita ajoesteiden tarpeen korvaamiseen ja määrittelemään ne tilanteet, joissa fyysisten ajoesteiden käyttö on edelleen perusteltavissa. Selvityksen mukaan ajoesteiden käytöstä ei tarvitse luopua kokonaan, mutta niiden käyttö toivotun liikennekäyttäytymisen varmistajana tulisi olla toissijaista. Ensisijaisesti tulisi pyrkiä suunnittelun ja toteutuksen kautta rakentamaan sellaista ympäristöä, joka vastaa asetettua sääntöympäristöä ja siten viestii kulkijalle oikeasta liikennekäyttäytymisestä. Esteiden käyttö oli huomattavan samankaltaista molemmissa tutkimuskaupungeissa, jonka perusteella voidaan olettaa, että tutkimuksessa esitetyt johtopäätelmät ja jatkosuositukset ovat kohtuullisen hyvin yleistettävissä myös muiden Suomen kaupunkien ja kuntien käytettäväksi. Tämän työn pohjalta ne voivat lähteä kehittämään omia toimintatapojaan ja suunnittelun tavoitteita ajoesteiden hallinnoinnin, määrän ja ympäristön laadun kannalta entistä paremmaksi.The thesis focused on the use of roadblocks as a part of the municipal street network structure. The aim of this thesis was to provide solutions and guidelines at the level of principle to replace the need for roadblocks and to identify situations where the use of physical barriers can be justified. Lahti and Vantaa acted as research cities and their practices on the use of roadblocks were examined through roadblock datasets cities composed and internal workshops. The structure of street network and the factors affecting the street space, as well as the construction and development of the traffic environment during different urban planning periods were examined in the literature review. In addition, the types of roadblocks, the legal basis and the use of roadblocks were surveyed through a few international examples. The case study analyzed the roadblock datasets. Analyzed factors were the type and the role of the barrier in the street network and the characteristics of the immediate environment. Clear categories of situations where roadblocks were repeatedly had to resort to were found. It emerged that in the majority of roadblock locations, the quality of the examined areas was unfinished and, for an example, the changes in traffic arrangements had not been implemented despite the installation of traffic signs and possible roadblocks. According to the study, the use of roadblocks must not be completely abandoned, but their use as a guarantee of the desired traffic behavior should be secondary. Priority should be given to designing and implementing an environment that meets the established rule environment and thus communicates to the traveler about the correct traffic behavior. The use of roadblocks was remarkably similar in both research cities, and the conclusions and recommendations presented in the study can be generalized to other Finnish cities and municipalities. Based on this work, the development of practices and design goals can be improved for better management, quantity and environmental quality of the roadblocks

A comprehensive model for measuring real-life cost-effectiveness in eyecare : automation in care and evaluation of system (aces-rwm (TM))

This paper describes a holistic, yet simple and comprehensible, ecosystem model to deal with multiple and complex challenges in eyecare. It aims at producing the best possible wellbeing and eyesight with the available resources. When targeting to improve the real-world cost-effectiveness, what gets done in everyday practice needs be measured routinely, efficiently and unselectively. Collection of all real-world data of all patients will enable evaluation and comparison of eyecare systems and departments between themselves nationally and internationally. The concept advocates a strategy to optimize real-life effectiveness, sustainability and outcomes of the service delivery in ophthalmology. The model consists of three components: (1) resource-governing principles (i.e., to deal with increasing demand and limited resources), (2) real-world monitoring (i.e., to collect structured real-world data utilizing automation and visualization of clinical parameters, health-related quality of life and costs), and (3) digital innovation strategy (i.e., to evaluate and benchmark real-world outcomes and cost-effectiveness). The core value and strength of the model lies in the consensus and collaboration of all Finnish university eye clinics to collect and evaluate the uniformly structured real-world outcomes data. In addition to ophthalmology, the approach is adaptable to any medical discipline to efficiently generate real-world insights and resilience in health systems.Peer reviewe

Oxidative Stress is the Principal Contributor to Inflammasome Activation in Retinal Pigment Epithelium Cells with Defunct Proteasomes and Autophagy

Background/Aims: Previously, we demonstrated that blockade of the intracellular clearance systems in human retinal pigment epithelial (RPE) cells by MG-132 and bafilomycin A1 (BafA) induces NLRP3 inflammasome signaling. Here, we have explored the activation mechanisms behind this process. NLRP3 is an intracellular receptor detecting factors ranging from the endogenous alarmins and adenosine triphosphate (ATP) to ultraviolet radiation and solid particles. Due to the plethora of triggers, the activation of NLRP3 is often indirect and can be mediated through several alternative pathways. Potassium efflux, lysosomal rupture, and oxidative stress are currently the main mechanisms associated with many activators. Methods: NLRP3 inflammasomes were activated in human RPE cells by blocking proteasomes and autophagy using MG-132 and bafilomycin A1 (BafA), respectively. P2X7 inhibitor A740003, potassium chloride (KCl), and glyburide, or N-acetyl-L-cysteine (NAC), ammonium pyrrolidinedithiocarbamate (APDC), diphenyleneiodonium chloride (DPI), and mito-TEMPO were added to cell cultures in order to study the role of potassium efflux and oxidative stress, respectively. IL-1β was measured using the ELISA method. ATP levels and cathepsin B activity were examined using commercial kits, and ROS levels using the fluorescent dye 2´,7´-dichlorodihydrofluorescein diacetate (DCFDA). Results: Elevated extracellular potassium prevented the priming factor IL-1α from inducing the production of reactive oxygen species (ROS). It also prevented IL-1β release after exposure of primed cells to MG-132 and BafA. Inflammasome activation increased extracellular ATP levels, which did not appear to trigger significant potassium efflux. The activity of the lysosomal enzyme, cathepsin B, was reduced by MG-132 and BafA, suggesting that cathepsin B was not playing any role in this phenomenon. Instead, MG-132 triggered ROS production already 30 min after exposure, but treatment with antioxidants blocking NADPH oxidase and mitochondria-derived ROS significantly prevented IL-1β release after this activating signal. Conclusion: Our data suggest that oxidative stress strongly contributes to the NLRP3 inflammasome activation upon dysfunctional cellular clearance. Clarification of inflammasome activation mechanisms provides novel options for alleviating pathological inflammation present in aggregation diseases, such as age-related macular disease (AMD) and Alzheimer’s disease

Ryhmämuotoiset vanhemmuusohjelmat ovat tuloksellisia lasten käyttäytymisen ongelmien hoidossa

• Ryhmämuotoiset vanhemmuutta tukevat ohjelmat ovat tuloksellinen tapa hoitaa lasten käyttäytymisen ongelmia.• Ne tehoavat parhaiten silloin, kun lapsen käyttäytymisen ongelmat ovat vakavia.• Tutkimusnäyttö viittaa siihen, että vanhemmuusohjelmia voidaan siirtää kulttuurista toiseen ilman suuria muutoksia.• Tulevaisuudessa tulisi tutkia vanhemmuusohjelmien pitkäaikaisvaikutuksia lapsen kehitykseen. Lisää tietoa tarvitaan myös siitä, miten ohjelmia voitaisiin muokata perheiden yksilöllisiin tarpeisiin sopivaksi.</p

A comprehensive model for measuring real-life cost-effectiveness in eyecare: automation in care and evaluation of system (aces-rwm™)

This paper describes a holistic, yet simple and comprehensible, ecosystem model to deal with multiple and complex challenges in eyecare. It aims at producing the best possible wellbeing and eyesight with the available resources. When targeting to improve the real-world cost-effectiveness, what gets done in everyday practice needs be measured routinely, efficiently and unselectively. Collection of all real-world data of all patients will enable evaluation and comparison of eyecare systems and departments between themselves nationally and internationally. The concept advocates a strategy to optimize real-life effectiveness, sustainability and outcomes of the service delivery in ophthalmology. The model consists of three components: (1) resource-governing principles (i.e., to deal with increasing demand and limited resources), (2) real-world monitoring (i.e., to collect structured real-world data utilizing automation and visualization of clinical parameters, health-related quality of life and costs), and (3) digital innovation strategy (i.e., to evaluate and benchmark real-world outcomes and cost-effectiveness). The core value and strength of the model lies in the consensus and collaboration of all Finnish university eye clinics to collect and evaluate the uniformly structured real-world outcomes data. In addition to ophthalmology, the approach is adaptable to any medical discipline to efficiently generate real-world insights and resilience in health systems

Ryhmämuotoiset vanhemmuusohjelmat ovat tuloksellisia lasten käyttäytymisen ongelmien hoidossa

Peer reviewe

Somatic MED12 Nonsense Mutation Escapes mRNA Decay and Reveals a Motif Required for Nuclear Entry

MED12 is a key component of the transcription-regulating Mediator complex. Specific missense and in-frame insertion/deletion mutations in exons 1 and 2 have been identified in uterine leiomyomas, breast tumors, and chronic lymphocytic leukemia. Here, we characterize the first MED12 5 end nonsense mutation (c.97G > T, p.E33X) identified in acute lymphoblastic leukemia and show that it escapes nonsense-mediated mRNA decay (NMD) by using an alternative translation initiation site. The resulting N-terminally truncated protein is unable to enter the nucleus due to the lack of identified nuclear localization signal (NLS). The absence of NLS prevents the mutant MED12 protein to be recognized by importin- and subsequent loading into the nuclear pore complex. Due to this mislocalization, all interactions between the MED12 mutant and other Mediator components are lost. Our findings provide new mechanistic insights into the MED12 functions and indicate that somatic nonsense mutations in early exons may avoid NMD. (C) 2017 Wiley Periodicals, Inc.Peer reviewe

Search for Microscopic Black Hole Signatures at the Large Hadron Collider

Peer reviewe