Novel biomarkers to predict response and prognosis in localized bladder cancer.

This review summarizes recent developments in diagnostic and prognostic biomarkers for nonmuscle invasive bladder cancer (NMIBC). Although the number of new biomarkers increases continuously, none are included in practice guidelines. Most NMIBC biomarkers show a higher sensitivity than urinary cytology, but lower specificity. Some protein and chromosome markers have been approved for screening and follow-up of patients in combination with cystoscopy. The long interval required for validation, testing, and approval of the assays and the lack of standardization could explain present issues in biomarker research. To enhance the development of new biomarkers, a more structured approach is required.

Order-flow Standardization with Product Data Management Ideology

Tämän diplomityön päämääränä oli kuvata tilaus-toimitusprosessin eri toimintojen työnkulku, kun tuotetiedonhallintajärjestelmä on osa työympäristöä. Työn teoreettisessa osassa tarkasteltiin liiketoimintaprosessien uudistamista ja prosessien määrittämistä sekä esiteltiin tuotetiedonhallinnan (PDM) keskeiset osa-alueet. Kohdeyrityksen tausta ja strategiat esiteltiin, minkä jälkeen muutoksia arvioitiin suhteessa teoriaosuuden tuloksiin. Nykyisten toimintatapojen määrittämistä varten haastateltiin henkilöitä jokaisesta tilaus-toimitusprosessin vaiheesta tuotantoyksikön sisällä. Lopuksi kuvattiin yrityksen tuotetiedonhallintaperiaatteet ja määritettiin työnkulku prosessin eri vaiheissa. Samalla kuin uusi tuotetiedonhallintajärjestelmä otetaan käyttöön, on yrityksessä omaksuttava tuotetiedonhallinnan ajatusmalli. Tuoterakenteen hallinta jakautuu nyt eri toimintojen kesken, jolloin suunnittelun rakenne, tuotannon rakenne ja huoltorakenne ovat eri ihmisten vastuulla. Näiden eri rakenteiden konfigurointi tilaus-toimitus prosessin aikana määrää missä järjestyksessä toiminnot on suoritettava eri järjestelmien välillä. Monikansallinen suunnitteluorganisaatio on myös otettava huomioon tilauksenkulun aikana. Tuotetiedonhallintajärjestelmää käytetään yhdessä tuttujen suunnitteluohjelmien sekä toiminnanohjausjärjestelmän (ERP) kanssa. Työnkulkukaaviossa määritellään koko yritystä koskeva malli siitä, miten ja missä järjestyksessä tehtävät on suoritettava eri järjestelmissä tilaus-toimitus prosessin aikana. Tässä työssä tutkittiin tuotteen määrittelyn ja suunnittelutiedon hallinnan kannalta oleellisimmat tilaus-toimitusprosessiin kuuluvat toiminnot; myynti, myynnin tuki, tuotannon ohjaus, sovellussuunnittelu ja dokumentointi. Tulevaisuudessa on suositeltavaa pohtia tuotetiedonhallintajärjestelmän käyttöönottoa myös tuotannossa ja ostoissa. Tilaus-toimitusprosessiin liittyvät kehitysmahdollisuudet kannattaisi seuraavaksi kohdistaa tilauksen määrittelyvaiheeseen myyjä-asiakas rajapinnassa, jossa tehdyt virheet kertautuvat jokaisessa prosessin vaiheessa.

Managing material flows and improving performance in a component supplier’s internal supply chain

Tämä diplomityö tehtiin osana Componenta Cast Componentsin kolmivuotista toimitusketjujen kehitysprojektia. Työn tavoitteena oli kuvata tyypillinen yrityksen sisäinen toimitusketjuprosessi ja tehdä alustava suorituskykyanalyysi valimon ja konepajan väliseen logistiseen prosessiin liittyen. Tarkoituksena oli myös löytää kehityskohteita materiaali- ja tietovirtojen hallinnassa näiden tuotantoyksiköiden välillä. Logistiikkaan, toimitusketjujen hallintaan ja toimitusketjun suorituskyvyn mittaamiseen liittyvän kirjallisuustutkimuksen sekä käytännön perusteella valittiin sopivat analyysimenetelmät. Näitä menetelmiä hyödynnettiin tilaustoimitus – prosessin kuvaamisessa sekä suorituskyvyn analysoinnissa yrityksen sisäisessä toimitusketjussa. Luonnollisena jatkona kehitettiin ja pantiin käytäntöön toimitusketjua synkronoiva imutyyppinen tuotannon- ja materiaalinohjausmenetelmä. Diplomityöprojektin aikana kehitettiin myös apuvälineet käyttöönotetun menetelmän asianmukaista hyödyntämistä varten. Diplomityöprojektissa otettiin ensimmäiset askeleet kohti integroitua sisäistä toimitusketjua. Uuden tuotannon- ja materiaalinohjausmenetelmän standardisointi muihin menetelmiin yhdistettynä, sekä toimitusketjun avainmittarien jatkokehitys on jo alkanut. Läpimenoaikoja lyhentämällä ja synkronoidun, läpinäkyvän kysyntä-tarjontaketjun avulla integroitumisen astetta voidaan nostaa edelleen. Poikkiorganisatorinen kehitys ja johtaminen toimitusketjussa on avainedellytys menestykseen.

An Evaluation of the Paper Profile - a comparative assessment of the applicability of an emerging environmental communication tool in pulp and paper industry

Diplomityön tavoitteena oli arvioida uutta sellu-, paperi- ja kartonkiteollisuuden Paper Profile -ympäristötuoteselostetta. Paper Profilen tarkoituksena on tarjota paperiteollisuuden asiakkaille ja muille kiinnostuneilla sidosryhmille yhtenäistä ympäristöinformaatiota koskien paperituotteiden koostumusta ja tuotteiden tärkeimpiä ympäristöparametrejä. Työn tärkein tavoite oli arvioida kriittisesti Paper Profilea ja verrata konseptia ISO:n, Kansainvälisen stardardisoimisliiton tuoteselosteeseen sekä löytää konseptien yhtäläisyydet ja erot. Tärkein tehtävä oli tunnistaa ne avaintekijät, joiden avulla Paper Profile -tuoteselostetta voitaisiin pitää yhtenevänä ISO/TR 14025 teknisen raportin kanssa. Lisäksi Paper Profile -tuoteselosteen mahdolliset kehittämistarpeet arvioitiin ISO-tuoteselosteen näkökulmasta. Työn toinen tavoite oli kerätä ja analysoida uuteen tuoteselosteeseen liittyvä asiakaspalaute ja verrata sitä Stora Enson tehtaiden ympäristöpäälliköiden antamiin Paper Profilea koskeviin kommentteihin. Työn tuloksena huomattiin, että Paper Profile -konsepti sellaisenaan ei ole kovin informatiivinen vaan tuoteseloste jättää monia ympäristökysymyksiä avoimeksi. Siitä huolimatta Paper Profile tarjoaa riittävän taustan eri paperituotteiden ympäristökuormitusten keskinäiselle vertailuille. Konseptin viestinnällinen näkökulma paranisi huomattavasti, jos tuoteselosteeseen lisättäisiin kolmannen osapuolen verifiointi. Lisäksi referenssiarvot kertoisivat asiakkaille paremmin esitettyjen parametrien taustoista. Stora Enson tehtaiden ympäristöpäälliköiden, samoin kuin asiakkaidenkin mielestä Paper Profile on yleisesti ottaen potentiaalinen ympäristöviestinnän työkalu, mutta silti konseptiin ehdotettiin joitakin pieniä muutoksia. Avoinna olevat metsäsertifiointikysymykset ja niiden puutteellinen tiedottaminen tuoteselosteessa puhututtivat sekä tehtaiden henkilöstöä että yritysasiakkaita.

Management of severe blunt hepatic injury in the era of computed tomography and transarterial embolization: A systematic review and critical appraisal of the literature.

BACKGROUND: During the last decade, the management of blunt hepatic injury has considerably changed. Three options are available as follows: nonoperative management (NOM), transarterial embolization (TAE), and surgery. We aimed to evaluate in a systematic review the current practice and outcomes in the management of Grade III to V blunt hepatic injury. METHOD: The MEDLINE database was searched using PubMed to identify English-language citations published after 2000 using the key words blunt, hepatic injury, severe, and grade III to V in different combinations. Liver injury was graded according to the American Association for the Surgery of Trauma classification on computed tomography (CT). Primary outcome analyzed was success rate in intention to treat. Critical appraisal of the literature was performed using the validated National Institute for Health and Care Excellence "Quality Assessment for Case Series" system. RESULTS: Twelve articles were selected for critical appraisal (n = 4,946 patients). The median quality score of articles was 4 of 8 (range, 2-6). Overall, the median Injury Severity Score (ISS) at admission was 26 (range, 0.6-75). A median of 66% (range, 0-100%) of patients was managed with NOM, with a success rate of 94% (range, 86-100%). TAE was used in only 3% of cases (range, 0-72%) owing to contrast extravasation on CT with a success rate of 93% (range, 81-100%); however, 9% to 30% of patients required a laparotomy. Thirty-one percent (range, 17-100%) of patients were managed with surgery owing to hemodynamic instability in most cases, with 12% to 28% requiring secondary TAE to control recurrent hepatic bleeding. Mortality was 5% (range, 0-8%) after NOM and 51% (range, 30-68%) after surgery. CONCLUSION: NOM of Grade III to V blunt hepatic injury is the first treatment option to manage hemodynamically stable patients. TAE and surgery are considered in a highly selective group of patients with contrast extravasation on CT or shock at admission, respectively. Additional standardization of the reports is necessary to allow accurate comparisons of the various management strategies. LEVEL OF EVIDENCE: Systematic review, level IV.

Secondhand tobacco smoke exposure in open and semi-open settings: a systematic review

Background: Some countries have recently extended smoke-free policies to particular outdoor settings; however, there is controversy regarding whether this is scientifically and ethically justifiable. Objectives: The objective of the present study was to review research on secondhand smoke (SHS) exposure in outdoor settings. Data sources: We conducted different searches in PubMed for the period prior to September 2012. We checked the references of the identified papers, and conducted a similar search in Google Scholar. Study selection: Our search terms included combinations of"secondhand smoke,""environmental tobacco smoke,""passive smoking" OR"tobacco smoke pollution" AND"outdoors" AND"PM" (particulate matter),"PM2.5" (PM with diameter ≤ 2.5 µm),"respirable suspended particles,""particulate matter,""nicotine,""CO" (carbon monoxide),"cotinine,""marker,""biomarker" OR"airborne marker." In total, 18 articles and reports met the inclusion criteria. Results: Almost all studies used PM2.5 concentration as an SHS marker. Mean PM2.5 concentrations reported for outdoor smoking areas when smokers were present ranged from 8.32 to 124 µg/m3 at hospitality venues, and 4.60 to 17.80 µg/m3 at other locations. Mean PM2.5 concentrations in smoke-free indoor settings near outdoor smoking areas ranged from 4 to 120.51 µg/m3. SHS levels increased when smokers were present, and outdoor and indoor SHS levels were related. Most studies reported a positive association between SHS measures and smoker density, enclosure of outdoor locations, wind conditions, and proximity to smokers. Conclusions: The available evidence indicates high SHS levels at some outdoor smoking areas and at adjacent smoke-free indoor areas. Further research and standardization of methodology is needed to determine whether smoke-free legislation should be extended to outdoor settings.

Estimating 750 years of temperature variations and uncertainties in the Pyrenees by tree-ring reconstructions and climate simulations.

Past temperature variations are usually inferred from proxy data or estimated using general circulation models. Comparisons between climate estimations derived from proxy records and from model simulations help to better understand mechanisms driving climate variations, and also offer the possibility to identify deficiencies in both approaches. This paper presents regional temperature reconstructions based on tree-ring maximum density series in the Pyrenees, and compares them with the output of global simulations for this region and with regional climate model simulations conducted for the target region. An ensemble of 24 reconstructions of May-to-September regional mean temperature was derived from 22 maximum density tree-ring site chronologies distributed over the larger Pyrenees area. Four different tree-ring series standardization procedures were applied, combining two detrending methods: 300-yr spline and the regional curve standardization (RCS). Additionally, different methodological variants for the regional chronology were generated by using three different aggregation methods. Calibration verification trials were performed in split periods and using two methods: regression and a simple variance matching. The resulting set of temperature reconstructions was compared with climate simulations performed with global (ECHO-G) and regional (MM5) climate models. The 24 variants of May-to-September temperature reconstructions reveal a generally coherent pattern of inter-annual to multi-centennial temperature variations in the Pyrenees region for the last 750 yr. However, some reconstructions display a marked positive trend for the entire length of the reconstruction, pointing out that the application of the RCS method to a suboptimal set of samples may lead to unreliable results. Climate model simulations agree with the tree-ring based reconstructions at multi-decadal time scales, suggesting solar variability and volcanism as the main factors controlling preindustrial mean temperature variations in the Pyrenees. Nevertheless, the comparison also highlights differences with the reconstructions, mainly in the amplitude of past temperature variations and in the 20th century trends. Neither proxy-based reconstructions nor model simulations are able to perfectly track the temperature variations of the instrumental record, suggesting that both approximations still need further improvements.

The Confidence Information Ontology: a step towards a standard for asserting confidence in annotations.

Biocuration has become a cornerstone for analyses in biology, and to meet needs, the amount of annotations has considerably grown in recent years. However, the reliability of these annotations varies; it has thus become necessary to be able to assess the confidence in annotations. Although several resources already provide confidence information about the annotations that they produce, a standard way of providing such information has yet to be defined. This lack of standardization undermines the propagation of knowledge across resources, as well as the credibility of results from high-throughput analyses. Seeded at a workshop during the Biocuration 2012 conference, a working group has been created to address this problem. We present here the elements that were identified as essential for assessing confidence in annotations, as well as a draft ontology--the Confidence Information Ontology--to illustrate how the problems identified could be addressed. We hope that this effort will provide a home for discussing this major issue among the biocuration community. Tracker URL: https://github.com/BgeeDB/confidence-information-ontology Ontology URL: https://raw.githubusercontent.com/BgeeDB/confidence-information-ontology/master/src/ontology/cio-simple.obo

La radiochirurgie dans le traitement de la douleur [Radiosurgery in Pain Treatment]

Le traitement de radiochirurgie par Gamma Knife (GK) est utilisé de plus en plus souvent comme une alternative à la microchirurgie conventionnelle pour le traitement des pathologies neurochirurgicales intracrâniennes. Il s'agit d'irradier en dose unique et à haute énergie, en condition stéréotaxique et à l'aide d'une imagerie multimodale (imagerie par résonance magnétique [IRM], tomodensitométrie et éventuellement artériographie). Le GK a été inventé par le neurochirurgien suédois Lars Leksell, qui a réalisé le premier ciblage du nerf trijumeau en 1951, sur la base d'une radiographie standard. Depuis, les progrès de l'informatique et de la robotique ont permis d'améliorer la technique de radiochirurgie qui s'effectue actuellement soit par accélérateur linéaire de particules monté sur un bras robotisé (Novalis®, Cyberknife®), soit par collimation de près de 192 sources fixes (GK). La principale indication radiochirurgicale dans le traitement de la douleur est la névralgie du nerf trijumeau. Les autres indications, plus rares, sont la névralgie du nerf glossopharyngien, l'algie vasculaire de la face, ainsi qu'un traitement de la douleur d'origine cancéreuse par hypophysiolyse. Gamma Knife surgery (GKS) is widely used as an alternative to open microsurgical procedures as noninvasive treatment of many intracranial conditions. It consists of delivering a single dose of high energy in stereotactic conditions, and with the help of a multimodal imaging (e.g., magnetic resonance imaging [MRI], computer tomography, and eventually angiography). The Gamma Knife (GK) was invented by the Swedish neurosurgeon Lars Leksell who was the first to treat a trigeminal neuralgia sufferer in 1951 using an orthogonal X-ray tube. Since then, the progresses made both in the field of informatics and robotics have allowed to improve the radiosurgical technique, which is currently performed either by a linear accelerator of particles mounted on a robotized arm (Novalis®, Cyberknife®), or by collimation of 192 fixed Co-60 sources (GK). The main indication of GKS in the treatment of pain is trigeminal neuralgia. The other indications, less frequent, are: glossopharyngeal neuralgia, cluster headache, and hypophysiolyse for cancer pain.

Tissue distribution of retinoids in common dolphins (Delphinus delphis).

Exposure to organochlorines induces retinoid deficiency in mammals; hence, retinoids are potential biomarkers of the impact of these pollutants. Appropriate target tissues to monitor retinoids in cetaceans have not been properly identified because of a lack of information on the contribution of each tissue to total body retinoids. Therefore, we have addressed this issue by studying the contribution of the main body tissues to retinoids in 21 common dolphins obtained from incidental catches and in apparent good health and nutritive condition. Although concentrations in the liver were highest, those in blubber were also high and accounted for 43% of the total retinoid load of the compartments examined. As blubber can be obtained using non-invasive biopsy techniques, this tissue is proposed as a reliable indicator of retinoid status in cetaceans. However, blubber topographical variation in structure and composition requires standardization of sampling sites. Retinoid concentrations did not differ significantly between sexes or with body size for any of the tissues, but the lipid content of blubber strongly influenced these concentrations. Biopsies from healthy, free-ranging individuals are preferred to samples from stranded animals. Further research on the influence of factors (age, sex, reproductive condition, diet) that potentially affect retinoid levels is required to implement the use of retinoids as biomarkers of pollutant exposure in cetaceans.

Improving anterior deltoid activity in a musculoskeletal shoulder model - an analysis of the torque-feasible space at the sternoclavicular joint.

Modelling the shoulder's musculature is challenging given its mechanical and geometric complexity. The use of the ideal fibre model to represent a muscle's line of action cannot always faithfully represent the mechanical effect of each muscle, leading to considerable differences between model-estimated and in vivo measured muscle activity. While the musculo-tendon force coordination problem has been extensively analysed in terms of the cost function, only few works have investigated the existence and sensitivity of solutions to fibre topology. The goal of this paper is to present an analysis of the solution set using the concepts of torque-feasible space (TFS) and wrench-feasible space (WFS) from cable-driven robotics. A shoulder model is presented and a simple musculo-tendon force coordination problem is defined. The ideal fibre model for representing muscles is reviewed and the TFS and WFS are defined, leading to the necessary and sufficient conditions for the existence of a solution. The shoulder model's TFS is analysed to explain the lack of anterior deltoid (DLTa) activity. Based on the analysis, a modification of the model's muscle fibre geometry is proposed. The performance with and without the modification is assessed by solving the musculo-tendon force coordination problem for quasi-static abduction in the scapular plane. After the proposed modification, the DLTa reaches 20% of activation.

Uncertainties in 4pi-gamma coincidence counting

The 4πβ-γ coincidence counting method and its close relatives are widely used for the primary standardization of radioactivity. Both the general formalism and specific implementation of these methods have been well-documented. In particular, previous papers contain the extrapolation equations used for various decay schemes, methods for determining model parameters and, in some cases, tabulated uncertainty budgets. Two things often lacking from experimental reports are both the rationale for estimating uncertainties in a specific way and the details of exactly how a specific component of uncertainty was estimated. Furthermore, correlations among the components of uncertainty are rarely mentioned. To fill in these gaps, the present article shares the best-practices from a few practitioners of this craft. We explain and demonstrate with examples of how these approaches can be used to estimate the uncertainty of the reported massic activity. We describe uncertainties due to measurement variability, extrapolation functions, dead-time and resolving-time effects, gravimetric links, and nuclear and atomic data. Most importantly, a thorough understanding of the measurement system and its response to the decay under study can be used to derive a robust estimate of the measurement uncertainty.

Uncertainty evaluation in activity measurements using ionization chambers

Pressurized re-entrant (or 4 pi) ionization chambers (ICs) connected to current-measuring electronics are used for activity measurements of photon emitting radionuclides and some beta emitters in the fields of metrology and nuclear medicine. As a secondary method, these instruments need to be calibrated with appropriate activity standards from primary or direct standardization. The use of these instruments over 50 years has been well described in numerous publications, such as the Monographie BIPM-4 and the special issue of Metrologia on radionuclide metrology (Ratel 2007 Metrologia 44 S7-16, Schrader1997 Activity Measurements With Ionization Chambers (Monographie BIPM-4) Schrader 2007 Metrologia 44 S53-66, Cox et al 2007 Measurement Modelling of the International Reference System (SIR) for Gamma-Emitting Radionuclides (Monographie BIPM-7)). The present work describes the principles of activity measurements, calibrations, and impurity corrections using pressurized ionization chambers in the first part and the uncertainty analysis illustrated with example uncertainty budgets from routine source-calibration as well as from an international reference system (SIR) measurement in the second part.

The economic cost of hospital malnutrition in Europe; a narrative review

Background: Malnutrition among hospitalized patients increases length of stay (LOS) and carries extra hospitalization costs. Objective: To review the impact of malnutrition on hospital LOS and costs in Europe. Methods: PubMed and Google Scholar search. All articles from January 2004 until November 2014 were identified. Reference lists of relevant articles were also manually searched. Results: Ten studies on LOS and nine studies on costs were reviewed. The methods used to assess malnutrition and to calculate costs differed considerably between studies. Malnutrition led to an increased LOS ranging from 2.4 to 7.2 days. Among hospitalized patients, malnutrition led to an additional individual cost ranging between 1640 V and 5829 V. At the national level, the costs of malnutrition ranged between 32.8 million V and 1.2 billion V. Expressed as percentage of national health expenditures, the values ranged between 2.1% and 10%. Conclusions: In Europe, malnutrition leads to an increase in LOS and in hospital costs, both at the individual and the national level. Standardization of methods and results reported is needed to adequately compare results between countries. © 2015 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Construction of an index of information from clinical practice in Radiology and Imaging Diagnosis based on text mining and thesaurus

Objective To construct a Portuguese language index of information on the practice of diagnostic radiology in order to improve the standardization of the medical language and terminology. Materials and Methods A total of 61,461 definitive reports were collected from the database of the Radiology Information System at Hospital das Clínicas – Faculdade de Medicina de Ribeirão Preto (RIS/HCFMRP) as follows: 30,000 chest x-ray reports; 27,000 mammography reports; and 4,461 thyroid ultrasonography reports. The text mining technique was applied for the selection of terms, and the ANSI/NISO Z39.19-2005 standard was utilized to construct the index based on a thesaurus structure. The system was created in *html. Results The text mining resulted in a set of 358,236 (n = 100%) words. Out of this total, 76,347 (n = 21%) terms were selected to form the index. Such terms refer to anatomical pathology description, imaging techniques, equipment, type of study and some other composite terms. The index system was developed with 78,538 *html web pages. Conclusion The utilization of text mining on a radiological reports database has allowed the construction of a lexical system in Portuguese language consistent with the clinical practice in Radiology.