Pre-analytical and methodological challenges in red blood cell microparticle proteomics.

Microparticles are phospholipid vesicles shed mostly in biological fluids, such as blood or urine, by various types of cells, such as red blood cells (RBCs), platelets, lymphocytes, endothelial cells. These microparticles contain a subset of the proteome of their parent cell, and their ready availability in biological fluid has raised strong interest in their study, as they might be markers of cell damage. However, their small size as well as their particular physico-chemical properties makes them hard to detect, size, count and study by proteome analysis. In this review, we report the pre-analytical and methodological caveats that we have faced in our own research about red blood cell microparticles in the context of transfusion science, as well as examples from the literature on the proteomics of various kinds of microparticles.

Challenges in lung transplantation.

Lung transplantation is an established therapy for end-stage pulmonary disorders in selected patients without significant comorbidities. The particular constraints associated with organ transplantation from deceased donors involve specific allocation rules in order to optimise the medical efficacy of the procedure. Comparison of different policies adopted by national transplant agencies reveals that an optimal and unique allocation system is an elusive goal, and that practical, geographical and logistic parameters must be taken into account. A solution to attenuate the imbalance between the number of lung transplant candidates and the limited availability of organs is to consider marginal donors. In particular, assessment and restoration of gas exchange capacity ex vivo in explanted lungs is a new and promising approach that some lung transplant programmes have started to apply in clinical practice. Chronic lung allograft dysfunction, and especially bronchiolitis obliterans, remains the major medium- and long-term problem in lung transplantation with a major impact on survival. Although there is to date no cure for established bronchiolitis obliterans, new preventive strategies have the potential to limit the burden of this feared complication. Unfortunately, randomised prospective studies are infrequent in the field of lung transplantation, and data obtained from larger studies involving kidney or liver recipients are not always relevant for this purpose.

Diagnostic and ethical challenges in disorders of consciousness and locked-in syndrome: a survey of German neurologists.

Diagnosis and decisions on life-sustaining treatment (LST) in disorders of consciousness, such as the vegetative state (VS) and the minimally conscious state (MCS), are challenging for neurologists. The locked-in syndrome (LiS) is sometimes confounded with these disorders by less experienced physicians. We aimed to investigate (1) the application of diagnostic knowledge, (2) attitudes concerning limitations of LST, and (3) further challenging aspects in the care of patients. A vignette-based online survey with a randomized presentation of a VS, MCS, or LiS case scenario was conducted among members of the German Society for Neurology. A sample of 503 neurologists participated (response rate 16.4%). An accurate diagnosis was given by 86% of the participants. The LiS case was diagnosed more accurately (94%) than the VS case (79%) and the MCS case (87%, p < 0.001). Limiting LST for the patient was considered by 92, 91, and 84% of the participants who accurately diagnosed the VS, LiS, and MCS case (p = 0.09). Overall, most participants agreed with limiting cardiopulmonary resuscitation; a minority considered limiting artificial nutrition and hydration. Neurologists regarded the estimation of the prognosis and determination of the patients' wishes as most challenging. The majority of German neurologists accurately applied the diagnostic categories VS, MCS, and LiS to case vignettes. Their attitudes were mostly in favor of limiting life-sustaining treatment and slightly differed for MCS as compared to VS and LiS. Attitudes toward LST strongly differed according to circumstances (e.g., patient's will opposed treatment) and treatment measures.

Comparison of the methodologies of paediatric peanut food challenges in England and Switzerland

Document Type: Meeting Abstract

Addressing current treatment challenges in Crohn's disease in real life: A physician's survey.

BACKGROUND: In recent years several trials have addressed treatment challenges in Crohn's disease. Clinical trials however, represent a very special situation. AIMS: To perform a cross-sectional survey among gastroenterologists on the current clinical real life therapeutic approach focussing on the use of biologics. METHODS: A survey including six main questions on clinical management of loss of response, diagnostic evaluation prior to major treatment changes, preference for anti-tumour necrosis factor (TNF) agent, (de-)escalation strategies as well as a basic section regarding personal information was sent by mail to all gastroenterologists in Switzerland (n=318). RESULTS: In total, 120 questionnaires were analysed (response rate 37.7%). 90% of gastroenterologists in Switzerland use a thiopurine as the first step-up strategy (anti-TNF alone 7.5%, combination 2.5%). To address loss of response, most physicians prefer shortening the interval of anti-TNF administration followed by dose increase, switching the biologic and adding a thiopurine. In case of prolonged remission on combination therapy, the thiopurine is stopped first (52.6%) after a mean treatment duration of 15.7 months (biologic first in 41.4%). CONCLUSIONS: Everyday clinical practice in Crohn's disease patients appears to be incongruent with clinical data derived from major trials. Studies investigating reasons underlying these discrepancies are of need to optimize and harmonize treatment.

Taking on new challenges in multi-word unit processing for Machine Translation

This paper discusses the qualitativecomparative evaluation performed on theresults of two machine translation systemswith different approaches to the processing ofmulti-word units. It proposes a solution forovercoming the difficulties multi-word unitspresent to machine translation by adopting amethodology that combines the lexicongrammar approach with OpenLogos ontologyand semantico-syntactic rules. The paper alsodiscusses the importance of a qualitativeevaluation metrics to correctly evaluate theperformance of machine translation engineswith regards to multi-word units.

Comparative genomics of emerging pathogens in the Candida glabrata clade

BACKGROUND: Candida glabrata follows C. albicans as the second or third most prevalent cause of candidemia worldwide. These two pathogenic yeasts are distantly related, C. glabrata being part of the Nakaseomyces, a group more closely related to Saccharomyces cerevisiae. Although C. glabrata was thought to be the only pathogenic Nakaseomyces, two new pathogens have recently been described within this group: C. nivariensis and C. bracarensis. To gain insight into the genomic changes underlying the emergence of virulence, we sequenced the genomes of these two, and three other non-pathogenic Nakaseomyces, and compared them to other sequenced yeasts. RESULTS: Our results indicate that the two new pathogens are more closely related to the non-pathogenic N. delphensis than to C. glabrata. We uncover duplications and accelerated evolution that specifically affected genes in the lineage preceding the group containing N. delphensis and the three pathogens, which may provide clues to the higher propensity of this group to infect humans. Finally, the number of Epa-like adhesins is specifically enriched in the pathogens, particularly in C. glabrata. CONCLUSIONS: Remarkably, some features thought to be the result of adaptation of C. glabrata to a pathogenic lifestyle, are present throughout the Nakaseomyces, indicating these are rather ancient adaptations to other environments. Phylogeny suggests that human pathogenesis evolved several times, independently within the clade. The expansion of the EPA gene family in pathogens establishes an evolutionary link between adhesion and virulence phenotypes. Our analyses thus shed light onto the relationships between virulence and the recent genomic changes that occurred within the Nakaseomyces.

Learning in Product Development Projects - Responding to challenges in global industrial company

Verkostoitunut kansainvälinen tuotekehitys on tärkeä osa menestystä nykypäivän muuttuvassa yritysmaailmassa. Toimintojen tehostamiseksi myös projektitoiminnot on sopeutettava kansainväliseen toimintaympäristöön. Kilpailukyvyn säilyttämiseksi projektitoimintoja on lisäksi jatkuvasti tehostettava. Yhtenäkeinona nähdään projektioppiminen, jota voidaan edistää monin eri tavoin. Tässätyössä keskitytään projektitiedonhallinnan kehittämisen tuomiin oppimismahdollisuuksiin. Kirjallisuudessa kerrotaan, että projektitiedon jakaminen ja sen hyödyntäminen seuraavissa projekteissa on eräs projektioppimisen edellytyksistä. Tämäon otettu keskeiseksi näkökulmaksi tässä tutkimuksessa. Lisäksi tutkimusalueen rajaamiseksi työ tarkastelee erityisesti projektioppimista kansainvälisten tuotekehitysprojektien välillä. Työn tavoitteena on esitellä keskeisiä projektioppimisen haasteita ja etsiä konkreettinen ratkaisu vastaamaan näihin haasteisiin. Tuotekehitystoiminnot ja kansainvälinen hajautettu projektiorganisaatio kohtaavat lisäksi erityisiä haasteita, kuten tiedon hajautuneisuus, projektihenkilöstön vaihtuvuus, tiedon luottamuksellisuus ja maantieteelliset haasteet (esim. aikavyöhykkeet ja toimipisteen sijainti). Nämä erityishaasteet on otettu huomioon ratkaisua etsittäessä. Haasteisiin päädyttiin vastaamaan tietotekniikkapohjaisella ratkaisulla, joka suunniteltiin erityisesti huomioiden esimerkkiorganisaation tarpeet ja haasteet. Työssä tarkastellaan suunnitellun ratkaisun vaikutusta projektioppimiseen ja kuinka se vastaa havaittuihin haasteisiin. Tuloksissa huomattiin, että projektioppimista tapahtui, vaikka oppimista oli vaikea suoranaisesti huomata tutkimusorganisaation jäsenten keskuudessa. Projektioppimista voidaan kuitenkin sanoa tapahtuvan, jos projektitieto on helposti koko projektiryhmän saatavilla ja se on hyvin järjesteltyä. Muun muassa nämä ehdot täyttyivät. Projektioppiminen nähdään yleisesti haastavana kehitysalueena esimerkkiorganisaatiossa. Suuri osa tietämyksestä on niin sanottua hiljaistatietoa, jota on hankala tai mahdoton saattaa kirjalliseen muotoon. Näin olleen tiedon siirtäminen jää suurelta osin henkilökohtaisen vuorovaikutuksen varaan. Siitä huolimatta projektioppimista on mahdollista kehittää erilaisin toimintamallein ja menetelmin. Kehitys vaatii kuitenkin resursseja, pitkäjänteisyyttä ja aikaa. Monet muutokset voivat vaatia myös organisaatiokulttuurin muutoksen ja vaikuttamista organisaation jäseniin. Motivaatio, positiiviset mielikuvat ja selkeät strategiset tavoitteet luovat vakaan pohjan projektioppimisen kehittämiselle.

Challenges in packaging waste management: A case study in the fast food industry

The main research problem of this thesis is to find out the means of promoting the recovery of packaging waste generated in thefast food industry. The recovery of packaging waste generated in the fast food industry is demanded by the packaging waste legislation and expected by the public. The means are revealed by the general factors influencing the recovery of packaging waste, analysed by a multidisciplinary literature review and a case study focusing on the packaging waste managementof McDonald's Oy operating in Finland. The existing solid waste infrastructure does not promote the recovery ofpackaging waste generated in the fast food industry. The theoretical recovery rate of the packaging waste is high, 93 %, while the actual recovery rate is only 29 % consisting of secondary packaging manufactured from cardboard. The total recovery potential of packaging waste is 64 %, resulting in 1 230 tonnes ofrecoverable packaging waste. The achievable recovery potential of 33 %, equalling 647 tonnes of packaging waste could be recovered, but is not recovered mainly because of non-working waste management practises. The theoretical recovery potential of 31 %, equalling 583 tonnes of packaging waste can not be recovered by the existing solid waste infrastructure because of the obscure status of commecial waste, the improper operation ofproducer organisations, and the municipal autonomy. The sorting experiment indicated that it is possible to reach the achievable recovery potential inthe existing solid waste infrastructure. The achievement is promoted by waste producer -oriented waste management practises. The theoretical recovery potential can be reached by increasing the consistency of the solid waste infrastructure through governmental action.

Challenges in co-operation with Logistics Service Providers

Kiristyvä kilpailu ja korkean teknologian alalle tyypillisten nopeiden suhdannevaihteluiden tuomat haasteet ajavat yrityksiä etsimään uusia kehityskohteita ja kustannussäästöjä. Ydinosaamisen ulkopuolelle kuuluvan osa-alueen ulkoistamisella yritykset hakevat tehokkuutta ja kustannussäästöjä eri toimintoihinsa. Tässä työssä selvitetään tutkittavan yrityksen toteutuneita ulkoistamisprojekteja, niiden tuomia etuja ja haittoja. Tutkimuksen teoriaosuudessa käsitellään yleisesti ulkoistamiseen liittyviä asioita, sekä uppoudutaan erityisesti logistiikan ulkoistamisen tuomiin mahdollisuuksiin ja haasteisiin. Empiirinen osuus käsittää prosessikuvaukset tutkittavan yrityksen logistisista toiminnoista sekä yrityksen toteutuneista ulkoistamisprojekteista. Vertailut -kappaleessa pohditaan mitä logistiikan ulkoistaminen on tarkoittanut sekä kustannus että operatiivisessa mielessä.