Defining the level of evidence for technology adoption in the localized prostate cancer pathway.

New technologies in prostate cancer are attempting to change the current prostate cancer pathway by aiming to reduce harms while maintaining the benefits associated with screening, diagnosis, and treatment. In this article, we discuss the optimal evaluation that new technologies should undergo to provide level 1 evidence typically required to change the practice. With this in mind, we focus on feasible and pragmatic trials that could be delivered in a timely fashion by many centers while retaining primary outcomes that focus on clinically meaningful outcomes.

Determination of picogram levels of midazolam, and 1- and 4-hydroxymidazolam in human plasma by gas chromatography-negative chemical ionization-mass spectrometry.

Midazolam is a widely accepted probe for phenotyping cytochrome P4503A. A gas chromatography-mass spectrometry (GC-MS)-negative chemical ionization method is presented which allows measuring very low levels of midazolam (MID), 1-OH midazolam (1OHMID) and 4-OH midazolam (4OHMID), in plasma, after derivatization with the reagent N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide. The standard curves were linear over a working range of 20 pg/ml to 5 ng/ml for the three compounds, with the mean coefficients of correlation of the calibration curves (n = 6) being 0.999 for MID and 1OHMID, and 1.0 for 4OHMID. The mean recoveries measured at 100 pg/ml, 500 pg/ml, and 2 ng/ml, ranged from 76 to 87% for MID, from 76 to 99% for 1OHMID, from 68 to 84% for 4OHMID, and from 82 to 109% for N-ethyloxazepam (internal standard). Intra- (n = 7) and inter-day (n = 8) coefficients of variation determined at three concentrations ranged from 1 to 8% for MID, from 2 to 13% for 1OHMID and from 1 to 14% for 4OHMID. The percent theoretical concentrations (accuracy) were within +/-8% for MID and 1OHMID, within +/-9% for 4OHMID at 500 pg/ml and 2 ng/ml, and within +/-28% for 4OHMID at 100 pg/ml. The limits of quantitation were found to be 10 pg/ml for the three compounds. This method can be used for phenotyping cytochrome P4503A in humans following the administration of a very low oral dose of midazolam (75 microg), without central nervous system side-effects.

Development and validation of a gas chromatography-negative chemical ionization tandem mass spectrometry method for the determination of ethyl glucuronide in hair and its application to forensic toxicology.

Ethyl glucuronide (EtG) is a minor and direct metabolite of ethanol. EtG is incorporated into the growing hair allowing retrospective investigation of chronic alcohol abuse. In this study, we report the development and the validation of a method using gas chromatography-negative chemical ionization tandem mass spectrometry (GC-NCI-MS/MS) for the quantification of EtG in hair. EtG was extracted from about 30 mg of hair by aqueous incubation and purified by solid-phase extraction (SPE) using mixed mode extraction cartridges followed by derivation with perfluoropentanoic anhydride (PFPA). The analysis was performed in the selected reaction monitoring (SRM) mode using the transitions m/z 347-->163 (for the quantification) and m/z 347-->119 (for the identification) for EtG, and m/z 352-->163 for EtG-d(5) used as internal standard. For validation, we prepared quality controls (QC) using hair samples taken post mortem from 2 subjects with a known history of alcoholism. These samples were confirmed by a proficiency test with 7 participating laboratories. The assay linearity of EtG was confirmed over the range from 8.4 to 259.4 pg/mg hair, with a coefficient of determination (r(2)) above 0.999. The limit of detection (LOD) was estimated with 3.0 pg/mg. The lower limit of quantification (LLOQ) of the method was fixed at 8.4 pg/mg. Repeatability and intermediate precision (relative standard deviation, RSD%), tested at 4 QC levels, were less than 13.2%. The analytical method was applied to several hair samples obtained from autopsy cases with a history of alcoholism and/or lesions caused by alcohol. EtG concentrations in hair ranged from 60 to 820 pg/mg hair.

Short-term stability of testosterone and epitestosterone conjugates in urine samples: quantification by liquid chromatography-linear ion trap mass spectrometry.

A simple method using liquid chromatography-linear ion trap mass spectrometry for simultaneous determination of testosterone glucuronide (TG), testosterone sulfate (TS), epitestosterone glucuronide (EG) and epitestosterone sulfate (ES) in urine samples was developed. For validation purposes, a urine containing no detectable amount of TG, TS and EG was selected and fortified with steroid conjugate standards. Quantification was performed using deuterated testosterone conjugates to correct for ion suppression/enhancement during ESI. Assay validation was performed in terms of lower limit of detection (1-3ng/mL), recovery (89-101%), intraday precision (2.0-6.8%), interday precision (3.4-9.6%) and accuracy (101-103%). Application of the method to short-term stability testing of urine samples at temperature ranging from 4 to 37 degrees C during a time-storage of a week lead to the conclusion that addition of sodium azide (10mg/mL) is required for preservation of the analytes.

Thérapie focale du cancer de la prostate: rationnel, résultats et perspectives [Focal therapy in prostate cancer: rationale, results and perspectives].

Focal therapy is a novel treatment strategy in prostate cancer aiming to treat only the area of the gland harbouring clinically significant disease. The overall objective is to maintain the oncological benefit of active treatment while minimising treatment-related morbidity. Leading centres are currently evaluating various minimally invasive technologies in a rigorous manner. Oncological and functional results in mid-term are encouraging with low rate of urinary incontinence and erectile dysfunction. However, the oncological outcome needs to be evaluated in the long-term in the light of the prolonged natural history of the disease.

UPLC-TOF-MS for plant metabolomics: a sequential approach for wound marker analysis in Arabidopsis thaliana.

The model plant Arabidopsis thaliana was studied for the search of new metabolites involved in wound signalling. Diverse LC approaches were considered in terms of efficiency and analysis time and a 7-min gradient on a UPLC-TOF-MS system with a short column was chosen for metabolite fingerprinting. This screening step was designed to allow the comparison of a high number of samples over a wide range of time points after stress induction in positive and negative ionisation modes. Thanks to data treatment, clear discrimination was obtained, providing lists of potential stress-induced ions. In a second step, the fingerprinting conditions were transferred to longer column, providing a higher peak capacity able to demonstrate the presence of isomers among the highlighted compounds.

A prospective development study investigating focal irreversible electroporation in men with localised prostate cancer: Nanoknife Electroporation Ablation Trial (NEAT).

INTRODUCTION: Focal therapy may reduce the toxicity of current radical treatments while maintaining the oncological benefit. Irreversible electroporation (IRE) has been proposed to be tissue selective and so might have favourable characteristics compared to the currently used prostate ablative technologies. The aim of this trial is to determine the adverse events, genito-urinary side effects and early histological outcomes of focal IRE in men with localised prostate cancer. METHODS: This is a single centre prospective development (stage 2a) study following the IDEAL recommendations for evaluating new surgical procedures. Twenty men who have MRI-visible disease localised in the anterior part of the prostate will be recruited. The sample size permits a precision estimate around key functional outcomes. Inclusion criteria include PSA ≤ 15 ng/ml, Gleason score ≤ 4 + 3, stage T2N0M0 and absence of clinically significant disease outside the treatment area. Treatment delivery will be changed in an adaptive iterative manner so as to allow optimisation of the IRE protocol. After focal IRE, men will be followed during 12 months using validated patient reported outcome measures (IPSS, IIEF-15, UCLA-EPIC, EQ-5D, FACT-P, MAX-PC). Early disease control will be evaluated by mpMRI and targeted transperineal biopsy of the treated area at 6 months. DISCUSSION: The NEAT trial will assess the early functional and disease control outcome of focal IRE using an adaptive design. Our protocol can provide guidance for designing an adaptive trial to assess new surgical technologies in the challenging landscape of health technology assessment in prostate cancer treatment.

Marketing education, distance learning and hypermedia : teaching 'current issues in marketing' in a virtual campus

This article reports on a project at the Universitat Oberta de Catalunya (UOC: The Open University of Catalonia, Barcelona) to develop an innovative package of hypermedia-based learning materials for a new course entitled 'Current Issues in Marketing'. The UOC is a distance university entirely based on a virtual campus. The learning materials project was undertaken in order to benefit from the advantages which new communication technologies offer to the teaching of marketing in distance education. The article reviews the main issues involved in incorporating new technologies in learning materials, the development of the learning materials, and their functioning within the hypermedia based virtual campus of the UOC. An empirical study is then carried out in order to evaluate the attitudes of students to the project. Finally, suggestions for improving similar projects in the future are put forward.

Enabling Java Connected Device Configuration in Symbian OS

Diplomityön tavoitteena on kehittää Java CDC ajoympäristo Symbian OS käyttöjärjestelmällä varustettuun mobiililaitteeseen. Ajoympäristön tarkoituksena on mahdollistaa kehittyneiden ajoympäristöjen ja sovellusten kehittäminen mobiililaitteiden Java ohjelmistoalustoihin. Diplomityö tarkastelee kahta mobiiliympäristöa, jotka ovat käytössä erittäin laajasti matkapuhelimissa ja kämmenmikroissa: Symbian OS ja Java. Symbian OS on mobiililaitteille tarkoitettu käyttöjärjestelmä, joka on tässä työssä alustana Java ajoympäristölle. Käytännön osuus kuvailee, kuinka CDC ajoympäristö voidaan toteuttaa mobiilissa Symbian OS ympäristössä. Työssä esitellään myös teknologioita, joita CDC ajoympäristön luomalle perustalle voidaan toteuttaa. Mobiililaitteiden ominaisuudet ovat kehittyneet huomattavasti sen jälkeen kun ensimmäiset CLDC ja MIDP Javaa tukevat laitteet tulivat markkinoille. Nykyisin matkapuhelimet ja kämmenmikrot alkavat muistuttaa ominaisuuksiltaan entistä enemmän tavallisia tietokoneita. Myös mobiililaitteiden Java ohjelmistoalustat tarvitsevat uusia teknologioita kasvaneiden vaatimusten tyydyttämiseksi.

VAL-Varastoinvestoinnit satamatoiminnassa. Case: Hamina Port Invest Oy

Tämän tutkielman päätavoitteena oli tutkia varastoinvestointitoimintaa ja sen mandollisuuksia Haminan satamassa. Teoreettinen osa jakautuu kahteen osa-alueeseen. Ensimmäisessä osassa käydään läpi investointien suunnittelua ja niiden taustoja, investoinnin kannattavuuteen vaikuttavia tekijöitä sekä suosituimpia investointilaskentamenetelmiä. Toisessa osassa keskitytään investointien rahoitukseen ja sen suunnitteluun Empiirinen aineisto muodostuu haastatteluista case-yrityksessä. Tutkimusote on normatiivinen. Tutkimuksessa on esitetty Hamina Port Invest Oy:n investointitoiminnan nykytila sekä investointitoimintaanvaikuttavat tekijät. Tutkimustulokset on esitetty tutkielman empiirisen osion lopuksi.

Measurement systems in wall production applications

Tässä tutkimuksessa kehitettiin prototyyppi betonielementin dimension mittaus järjestelmästä. Tämä järjestelmä mahdollistaa kolmiulotteisen kappaleen mittauksen. Tutkimuksessa kehitettiin myös stereonäköön perustuva kappaleen mittaus. Prototyyppiä testailin ja tulokset osoittautuivat luotettaviksi. Tutkimuksessa selvitetään ja vertaillaan myös muita lähestymistapoja ja olemassa olevia järjestelmiä kappaleen kolmiuloitteiseen mittaukseen, joita Suomalaiset yhtiöt käyttävät tällä alalla.

Beyond the net generation debate: A comparison of digital learners in face-to-face and virtual universities

In the last decade, an important debate has arisen about the characteristics of today"s students due to their intensive experience as users of ICT. The main belief is that frequent use of technologies in everyday life implies that competent users are able to transfer their digital skills to learning activities. However, empirical studies developed in different countries reveal similar results suggesting that the"digital native" label does not provide evidence of a better use of technology to support learning. The debate has to go beyond the characteristics of the new generation and focus on the implications of being a learner in a digitalised world. This paper is based on the hypothesis that the use of technology to support learning is not related to whether a student belongs to the Net Generation, but that it is mainly influenced by the teaching model. The study compares behaviour and preferences towards ICT use in two groups of university students: face-to-face students and online students. A questionnaire was applied to a sample of students from five universities with different characteristics (one offers online education and four offer face-to-face education with LMS teaching support). Findings suggest that although access to and use of ICT is widespread, the influence of teaching methodology is very decisive. For academic purposes, students seem to respond to the requirements of their courses, programmes, and universities. There is a clear relationship between students" perception of usefulness regarding certain ICT resources and their teachers" suggested uses of technologies. The most highly rated technologies correspond with those proposed by teachers. The study shows that the educational model (face-to-face or online) has a stronger influence on students" perception of usefulness regarding ICT support for learning than the fact of being a digital native.

Use of scenario analysis in studying emerging technology – Case Grid computing

Tutkimuksen selvitettiin miten skenaarioanalyysia voidaan käyttää uuden teknologian tutkimisessa. Työssä havaittiin, että skenaarioanalyysin soveltuvuuteen vaikuttaa eniten teknologisen muutoksen taso ja saatavilla olevan tiedon luonne. Skenaariomenetelmä soveltuu hyvin uusien teknologioiden tutkimukseen erityisesti radikaalien innovaatioiden kohdalla. Syynä tähän on niihin liittyvä suuri epävarmuus, kompleksisuus ja vallitsevan paradigman muuttuminen, joiden takia useat muut tulevaisuuden tutkimuksen menetelmät eivät ole tilanteessa käyttökelpoisia. Työn empiirisessä osiossa tutkittiin hilaverkkoteknologian tulevaisuutta skenaarioanalyysin avulla. Hilaverkot nähtiin mahdollisena disruptiivisena teknologiana, joka radikaalina innovaationa saattaa muuttaa tietokonelaskennan nykyisestä tuotepohjaisesta laskentakapasiteetin ostamisesta palvelupohjaiseksi. Tällä olisi suuri vaikutus koko nykyiseen ICT-toimialaan erityisesti tarvelaskennan hyödyntämisen ansiosta. Tutkimus tarkasteli kehitystä vuoteen 2010 asti. Teorian ja olemassa olevan tiedon perusteella muodostettiin vahvaan asiantuntijatietouteen nojautuen neljä mahdollista ympäristöskenaariota hilaverkoille. Skenaarioista huomattiin, että teknologian kaupallinen menestys on vielä monen haasteen takana. Erityisesti luottamus ja lisäarvon synnyttäminen nousivat tärkeimmiksi hilaverkkojen tulevaisuutta ohjaaviksi tekijöiksi.

e-Justice in Spain

Technology has had a prevalent impact on nearly all social domains, one being the judicial system. Advancements such as computer-generated demonstrations and electronic filing can enhance presentations and give a clearer, well-organized case.E-Justice: Using Information Communication Technologies in the Court System presents the most relevant experiences and best practices concerning the use and impact of ICTs in the courtroom. This groundbreaking title draws upon the leading academic and practicing perspectives from around the globe to provide academics and professionals throughout the legal system with the most comprehensive overview of present developments in e-justice.