Communicating Highway Safety: What Works, 2002

Few topics in transportation are of greater significance, now and in the future, than making today’s roads safe for those who use them. This study aims to assist the formulation of policy by examining the empirical evidence currently available on the ability of several forms of communication efforts and activities to increase knowledge about and affect attitudes and behavior toward highway safety practices. The objective of this effort is to provide a comparative synthesis of what works and what does not in highway safety campaigns across a large number of topical areas that have a mass media component. This was accomplished by conducting an extensive literature review to determine the current state of knowledge concerning what works and what has significant potential for wide use in future highway safety campaigns. An analytic framework for investigating highway safety campaigns was created. The framework includes (1) the types of media components, (2) the types of collaborations, (3) the context in which the campaign is intended to have impact, (4) the structure or procedural steps into which campaigns are organized, (5) the principles for what works in a campaign, and (6) the desired impact of a campaign on its target audience. The report reveals 25 characteristics of successful communication campaigns, strategies that stand a chance of achieving changes in knowledge, attitude, and behavior. The actual impact of mass communication remains unproven because of a perceived lag in the development of adequate evaluation techniques. Education by itself has not generally resulted in significant changes in the behaviors targeted, but education of the public and advocacy groups has often helped enact necessary legislation, transmit knowledge about the provisions and penalties of laws in ways that increase their deterrent effect, and generate public support for law enforcement programs. Even in such cases, however, when enforcement is inconsistent, public compliance frequently decreases with time. Approaches to traffic safety that emphasize the need for long-term individual- and community-based measures are found to be especially crucial for addressing complex problems like drinking and driving that are determined by a myriad of lifestyle and psychosocial factors.

Toxicokinetic modeling of folpet fungicide and its ring-biomarkers of exposure in humans.

A human in vivo toxicokinetic model was built to allow a better understanding of the toxicokinetics of folpet fungicide and its key ring biomarkers of exposure: phthalimide (PI), phthalamic acid (PAA) and phthalic acid (PA). Both PI and the sum of ring metabolites, expressed as PA equivalents (PAeq), may be used as biomarkers of exposure. The conceptual representation of the model was based on the analysis of the time course of these biomarkers in volunteers orally and dermally exposed to folpet. In the model, compartments were also used to represent the body burden of folpet and experimentally relevant PI, PAA and PA ring metabolites in blood and in key tissues as well as in excreta, hence urinary and feces. The time evolution of these biomarkers in each compartment of the model was then mathematically described by a system of coupled differential equations. The mathematical parameters of the model were then determined from best fits to the time courses of PI and PAeq in blood and urine of five volunteers administered orally 1 mg kg(-1) and dermally 10 mg kg(-1) of folpet. In the case of oral administration, the mean elimination half-life of PI from blood (through feces, urine or metabolism) was found to be 39.9 h as compared with 28.0 h for PAeq. In the case of a dermal application, mean elimination half-life of PI and PAeq was estimated to be 34.3 and 29.3 h, respectively. The average final fractions of administered dose recovered in urine as PI over the 0-96 h period were 0.030 and 0.002%, for oral and dermal exposure, respectively. Corresponding values for PAeq were 24.5 and 1.83%, respectively. Finally, the average clearance rate of PI from blood calculated from the oral and dermal data was 0.09 ± 0.03 and 0.13 ± 0.05 ml h(-1) while the volume of distribution was 4.30 ± 1.12 and 6.05 ± 2.22 l, respectively. It was not possible to obtain the corresponding values from PAeq data owing to the lack of blood time course data.

Prurigo nodularis: retrospective study of 13 cases managed with methotrexate.

BACKGROUND: Prurigo nodularis (PN), or nodular prurigo, is a chronic, debilitating, inflammatory skin disease. It can be very difficult to manage, and represents a challenge for the physician. Methotrexate (MTX) is a safe folic acid antagonist widely used in the management of inflammatory skin diseases such as psoriasis. Weekly administration of 7.5-20 mg methotrexate (low-dose methotrexate, LD-MTX) represents an attractive treatment option, and could therefore find a place in the management of PN. AIM: To evaluate the efficacy of LD-MTX as a treatment option for PN. METHODS: Thirteen patients who had failed to respond to conventional therapies such as topical steroids, phototherapy and antipruritic agents were treated with LD-MTX. The mean age of the patients was 75.83. Objective symptoms (Prurigo Nodularis Area and Severity Index; PNASI) and subjective symptoms (Pruritus Numeric Rating Scale; PNRS) were recorded. Treatment consisted of one subcutaneous injection of MTX 7.5-20 mg once weekly for a minimum of 6 months. Adjuvant application of emollients and topical steroids was maintained where needed. RESULTS: There was remission or marked improvement (decrease in both PNRS or PNASI of > 75%) in 10 cases, a trend to improvement in 2 cases and relapse in 1 case after treatment discontinuation. CONCLUSIONS: LD-MTX may allow improvement of PN in some patients, with long-lasting remission.

Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors.

BACKGROUND: It has been proposed that the innate immune system plays a central role in driving the autoimmune T-cell cascade leading to psoriasis; however, there is no direct evidence for this. OBSERVATIONS: We observed aggravation and spreading of a psoriatic plaque when treated topically with the toll-like receptor (TLR) 7 agonist imiquimod. The exacerbation of psoriasis was accompanied by a massive induction of lesional type I interferon activity, detected by MxA expression after imiquimod therapy. Since imiquimod induces large amounts of type I interferon production from TLR7-expressing plasmacytoid dendritic cell precursors (PDCs), the natural interferon-producing cells of the peripheral blood, we asked whether PDCs are present in psoriatic skin. We identified high numbers of PDCs in psoriatic skin lesions (up to 16% of the total dermal infiltrate) based on their coexpression of BDCA2 and CD123. By contrast, PDCs were present at very low levels in atopic dermatitis and not detected in normal human skin. CONCLUSIONS: This study shows that psoriasis can be driven by the innate immune system through TLR ligation. Furthermore, our finding that large numbers of PDCs infiltrate psoriatic skin suggests a role of lesional PDCs as type I interferon-producing targets for the TLR7 agonist imiquimod.

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The expansion of international standardization has reinforced enduring questions on the legitimacy of standards. In that respect, the participation of all stakeholders, including the weakest ones (unions, NGO, consumers' associations) is crucial. Given the recognized role of consumers' associations to express legitimate objectives, the question of their representation becomes central. In order to get a deeper understanding of their participation, this article explores the evolution of their representation within the Swiss national mirror committees of international standardization between 1987 and 2007. It probes the extent to which their participation is determined by the distinctiveness of issues supposedly related to consumers' concerns and by their own use of standards. The empirical findings of our study indicate an underrepresentation of consumers' associations and confirm the topical specificity of their implication in standardization processes. Finally, we found evidence that the use of standards in an association's activities supports and encourages its participation in standardization committees.

Cyclosporine A delivery to the eye: a pharmaceutical challenge.

Systemic administration of cyclosporine A (CsA) is commonly used in the treatment of local ophthalmic conditions involving cytokines, such as corneal graft rejection, autoimmune uveitis and dry eye syndrome. Local administration is expected to avoid the various side effects associated with systemic delivery. However, the currently available systems using oils to deliver CsA topically are poorly tolerated and provide a low bioavailability. These difficulties may be overcome through formulations aimed at improving CsA water solubility (e.g. cyclodextrins), or those designed to facilitate tissue drug penetration using penetration enhancers. The use of colloidal carriers (micelles, emulsions, liposomes and nanoparticles) as well as the approach using hydrosoluble prodrugs of CsA have shown promising results. Solid devices such as shields and particles of collagen have been investigated to enhance retention time on the eye surface. Some of these topical formulations have shown efficacy in the treatment of extraocular diseases but were inefficient at reaching intraocular targets. Microspheres, implants and liposomes have been developed to be directly administered subconjunctivally or intravitreally in order to enhance CsA concentration in the vitreous. Although progress has been made, there is still room for improvement in CsA ocular application, as none of these formulations is ideal.

Profiling of steroid metabolites after transdermal and oral administration of testosterone by ultra-high pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

The screening of testosterone (T) misuse for doping control is based on the urinary steroid profile, including T, its precursors and metabolites. Modifications of individual levels and ratio between those metabolites are indicators of T misuse. In the context of screening analysis, the most discriminant criterion known to date is based on the T glucuronide (TG) to epitestosterone glucuronide (EG) ratio (TG/EG). Following the World Anti-Doping Agency (WADA) recommendations, there is suspicion of T misuse when the ratio reaches 4 or beyond. While this marker remains very sensitive and specific, it suffers from large inter-individual variability, with important influence of enzyme polymorphisms. Moreover, use of low dose or topical administration forms makes the screening of endogenous steroids difficult while the detection window no longer suits the doping habit. As reference limits are estimated on the basis of population studies, which encompass inter-individual and inter-ethnic variability, new strategies including individual threshold monitoring and alternative biomarkers were proposed to detect T misuse. The purpose of this study was to evaluate the potential of ultra-high pressure liquid chromatography (UHPLC) coupled with a new generation high resolution quadrupole time-of-flight mass spectrometer (QTOF-MS) to investigate the steroid metabolism after transdermal and oral T administration. An approach was developed to quantify 12 targeted urinary steroids as direct glucuro- and sulfo-conjugated metabolites, allowing the conservation of the phase II metabolism information, reflecting genetic and environmental influences. The UHPLC-QTOF-MS(E) platform was applied to clinical study samples from 19 healthy male volunteers, having different genotypes for the UGT2B17 enzyme responsible for the glucuroconjugation of T. Based on reference population ranges, none of the traditional markers of T misuse could detect doping after topical administration of T, while the detection window was short after oral TU ingestion. The detection ability of the 12 targeted steroids was thus evaluated by using individual thresholds following both transdermal and oral administration. Other relevant biomarkers and minor metabolites were studied for complementary information to the steroid profile, including sulfoconjugated analytes and hydroxy forms of glucuroconjugated metabolites. While sulfoconjugated steroids may provide helpful screening information for individuals with homozygotous UGT2B17 deletion, hydroxy-glucuroconjugated analytes could enhance the detection window of oral T undecanoate (TU) doping.

Résultats à deux ans de la trabéculoplastie sélective au laser dans le glaucome à angle ouvert et l'hypertonie oculaire

BACKGROUND: Selective laser trabeculoplasty (SLT) is a relatively new treatment strategy for the treatment of glaucoma. Its principle is similar to that of argon laser trabeculoplasty (ALT), but may lead to less damage to the trabecular meshwork. METHODS: We assessed the 2-year efficacy of SLT in a noncomparative consecutive case series. Any adult patient either suspected of having glaucoma or with open-angle glaucoma, whose treatment was judged insufficient to reach target intraocular pressure (IOP), could be recruited. IOP and number of glaucoma treatments were recorded over 2 years after the procedure. RESULTS: Our sample consisted of 44 consecutive eyes of 26 patients, aged 69+/-8 years. Eyes were treated initially on the lower 180 degrees . Three of them were retreated after 15 days on the upper 180. Fourteen eyes had ocular hypertension, 17 primary open-angle/normal-tension glaucoma, 11 pseudoexfoliation (PEX) glaucoma, and two pigmentary glaucoma. Thirty-six eyes had previously been treated and continued to be treated with topical anti-glaucoma medication, ten had had prior ALT, nine iridotomy, and 12 filtering surgery. The 2-year-follow up could not be completed for eight eyes because they needed filtering surgery. In the remaining 36 eyes, IOP decreased by a mean of 17.2%, 3.3 mmHg, (19.2+/-4.7 to 15+/-3.6 mmHg) after 2 years (p<0.001). As a secondary outcome, the number of glaucoma treatments decreased from 1.44 to 1.36 drops/patient. Other results according to subgroups of patients are analyzed: the greatest IOP decrease occurred in eyes that had never been treated with anti-glaucoma medication or with PEX glaucoma. SLT was probably valuable in a few eyes after filtering surgery; however, the statistical power of the study was not strong enough to draw a firm conclusion. When expressed in survival curves after 2 years, however, only 48% and 41% of eyes experienced a decrease of more than 3 mmHg or more than 20% of preoperative intraocular pressure, respectively. CONCLUSION: SLT decreases IOP somewhat for at least 2 years without an increase in topical glaucoma treatment. However, it cannot totally replace topical glaucoma treatment. In the future, patient selection should be improved to decrease the cost/effectiveness ratio.

Ornament of Reason : an annoted english translation of rMa bya Byang chub brtson 'grus's : commentary to the Mūlamadhyamakakārikā

The present work contains an English translation of the Ornament of Reason (Tib. dBu ma'i rtsa ba shes rab kyi 'grel ba thad pa'i rgyan), an influential 12th century Tibetan commentary to a classic of Indian Buddhism, Nàgàrjuna's Root of the Middle Way (Skt. Mûlamadhyamaka-kârikâ Tib. dBu ma'i rtsa ba shes rab ces bya ba). The author, rMa bya byang chub brtson 'grus's, was among the first Tibetans to explicitly align themselves with the philosophical project of the 7th century Indian Madhyamaka teacher, CandrakTrti. With his stern revision and transformative re-employment of the epistemological framework that CandrakTrti otherwise scorns, rMa bya was however to develop an original and highly influential Madhyamaka interpretation.¦rMa bya's "topical outline" (Tib. sa bead) of his commentary is contained in the first appendix to the translation. The second appendix contains a digitalized version of the Rumtek edition of rMa bya's commentary, cross-referenced to the page numbers of the translation. The annotations contain concise explanatory remarks and suggestions for further reading, as well as identifications of the passages that rMa bya cites.

Lainattu todellisuus : tekijän huomioita ajankohtaisteatterista

Opinnäytetyöni käsittelee ajankohtaisteatteria. Tarkoituksenani on koettaa määritellä mitä käsite ajankohtaisteatteri tarkoittaa ja löytää niitä erityispiirteitä mitkä mahdollisesti erottavat ajankohtaisteatteriksi luettavat esitykset muusta teatteritaiteesta. Päätutkimuskohteeni on kirjoittamani ja ohjaamani näytelmä Markus - Elo Kuva. Työni alussa puran auki seikkaperäisesti koko Markus - Elo Kuvan syntyprosessin. Selvitän mistä todellisista tapahtumasta näytelmän idea sai alkunsa ja miten kirjoittamisprosessi eteni. Kerron myös miten ja millaisella aikataululla näytelmä saatettiin näyttämölle ja minkälaisen vastaanoton se sai. Esiteltyäni päätutkimuskohteeni tarkastelen ylipäätään teatterin suhdetta aikaan ja ympäröivään todellisuuteen, ja koetan määrittää niitä ulkoisia tunnusmerkkejä ja erityispiirteitä mitkä erottavat ajankohtaisteatteriksi laskettavat esitykset muusta teatteritaiteesta. Ulkoisten tunnuspiirteitten jälkeen siirryn pohtimaan ajankohtaisteatterin tekijän motiiveja, ja esitän teoriani ajankohtaisteatterin dialektisestä luonteesta. Selvennän teoriaani purkamalla Markus - Elo Kuvan useassa kerroksessa näkyvää dialektista rakennetta. Tarkastelen myös ajankohtaisteatteriksi laskettavien esitysten teosrajaa, mikä on nähdäkseni poikkeuksellinen verrattuna muuhun teatteritaiteeseen.

Utilisation of Statistics in Intelligent Web Applications

Web-portaalien aiheenmukaista luokittelua voidaan hyödyntää tunnistamaan käyttäjän kiinnostuksen kohteet keräämällä tilastotietoa hänen selaustottumuksistaan eri kategorioissa. Tämä diplomityö käsittelee web-sovelluksien osa-alueita, joissa kerättyä tilastotietoa voidaan hyödyntää personalisoinnissa. Yleisperiaatteet sisällön personalisoinnista, Internet-mainostamisesta ja tiedonhausta selitetään matemaattisia malleja käyttäen. Lisäksi työssä kuvaillaan yleisluontoiset ominaisuudet web-portaaleista sekä tilastotiedon keräämiseen liittyvät seikat.

Comparison of three separate antiadhesive barriers for intraperitoneal onlay mesh hernia repair in an experimental model (Br J Surg 2011; 98: 442-449).

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (www.bjs.co.uk). All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length.

Höyrynkehitin-vedenlämmitin-energialaitoksen kunnossapidon tuotteistaminen

Työn tavoitteena on luoda ehdotus toimintamalliksi, jolla Polarmatic Oy:n valmistaman Turbomatic-energialaitoksen kunnossapitotoimintaa voitaisiin suorittaa. Kunnossapito on yrityksessä mielenkiinnon kohteena, koska asiakkaiden suunnalta on asiaa kohtaan ollut kiinnostusta. Toimintamallia on tarkoitus muuttaa vikoja ehkäiseväksi ja suunnitelmallisemmaksi. Nykyinen käyttö vikaantumiseen asti aiheuttaa ennakoimatonta korjaustarvetta. Työssä tutustutaan kunnossapitopalvelun tuotteistamiseen ja tuotteistamisprosessiin. Palvelun tuotteistaminen on prosessi, jossa asiakkaalle tarjottava palvelumääritellään, suunnitellaan ja kuvataan. Asiantuntijapalvelun, tässä tapauksessa kunnossapitopalvelun, tarjoaminen lähtee aina tuotteen syvällisestä tuntemuksesta. Turbomaticin kunnossapidon suunnittelua varten työssä käydään läpi energialaitoksen tekninen kuvaus, huoltokohteet ja vikaantuminen. Tiedot on kerätty Polarmaticin henkilökunnan haastatteluista. Kunnossapidon teoriaan ja palvelun tuotteistamiseen tutustutaan kirjallisuuden ja ajankohtaisen lähdemateriaalin avulla. Lisäksi työssä perehdytään muiden yritysten tarjoamiin kunnossapitopalveluihin internetsivuilta. Tulokseksi työstä saadaan toimintaehdotus kunnossapidon järjestämisestä. Vuosihuollon suorittamista varten on työssä liitteenä vuosihuollon tarkastuspöytäkirja. Lisäksi vuosihuoltotarjousten tekoa varten on tehty laskentaohjelma.

Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients.

Optimal vaccine strategies must be identified for improving T-cell vaccination against infectious and malignant diseases. MelQbG10 is a virus-like nano-particle loaded with A-type CpG-oligonucleotides (CpG-ODN) and coupled to peptide(16-35) derived from Melan-A/MART-1. In this phase IIa clinical study, four groups of stage III-IV melanoma patients were vaccinated with MelQbG10, given (i) with IFA (Montanide) s.c.; (ii) with IFA s.c. and topical Imiquimod; (iii) i.d. with topical Imiquimod; or (iv) as intralymph node injection. In total, 16/21 (76%) patients generated ex vivo detectable Melan-A/MART-1-specific T-cell responses. T-cell frequencies were significantly higher when IFA was used as adjuvant, resulting in detectable T-cell responses in all (11/11) patients, with predominant generation of effector-memory-phenotype cells. In turn, Imiquimod induced higher proportions of central-memory-phenotype cells and increased percentages of CD127(+) (IL-7R) T cells. Direct injection of MelQbG10 into lymph nodes resulted in lower T-cell frequencies, associated with lower proportions of memory and effector-phenotype T cells. Swelling of vaccine site draining lymph nodes, and increased glucose uptake at PET/CT was observed in 13/15 (87%) of evaluable patients, reflecting vaccine triggered immune reactions in lymph nodes. We conclude that the simultaneous use of both Imiquimod and CpG-ODN induced combined memory and effector CD8(+) T-cell responses.

Prosessien hallinnastako avain tuloksellisempaan valtionhallintoon?

Valtionhallinnon muutosprosessissa on huomattu tulosohjaukseen liittyvät rakenteelliset ongelmat. 2000-luvun puolivälissä prosessiajattelu nousee uudelleen esiin. Sitä esitetään aidosti ratkaisumalliksi julkisten palvelujen järjestämiseen. Prosessit ovattulleet ajankohtaisiksi. Tutkielman päätavoitteena oli prosessijohtamisen ja muutosjohtamisen lähtökohtien syventäminen. Alatavoitteina olivat prosessien suoritusmittarit ja onnistuneen muutoshallinnan avaintekijät. Tutkimus perustuu lähdekirjallisuuteen ja asiantuntijoiden haastatteluihin. Prosessilähtöisyys valtionhallinnossa on huomion kiinnittämistä ulkoisen asiakkaan tarpeiden tyydyttämiseen sekä yhteiskunnallisten vaikuttavuustavoitteiden saavuttamiseen. Muutos vaatiinimenomaan johtamista sekä sitkeyttä ja vastarinnan sietämistä. Lisäksi se vaatii johdon sitoutumista ja määrätietoista työtä tavoitteiden saavuttamiseksi. Rohkeus ja avoimuus uusille asioille ovat myös tärkeitä. Valtionhallinnon organisaatioissa tarvitaan lähitulevaisuudessa entistä enemmän muutosagentteja, muutosjohtajia ja uudenlaista osaamista.