Ultra-performance liquid chromatography mass spectrometry and sensitive bioassay methods for quantification of posaconazole plasma concentrations after oral dosing.

Posaconazole (POS) is a new antifungal agent for prevention and therapy of mycoses in immunocompromised patients. Variable POS pharmacokinetics after oral dosing may influence efficacy: a trough threshold of 0.5 ?g/ml has been recently proposed. Measurement of POS plasma concentrations by complex chromatographic techniques may thus contribute to optimize prevention and management of life-threatening infections. No microbiological analytical method is available. The objective of this study was to develop and validate a new simplified ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method and a sensitive bioassay for quantification of POS over the clinical plasma concentration range. The UPLC-MS/MS equipment consisted of a triple quadrupole mass spectrometer, an electrospray ionization (ESI) source, and a C(18) analytical column. The Candida albicans POS-hypersusceptible mutant (MIC of 0.002 ?g/ml) ?cdr1 ?cdr2 ?flu ?mdr1 ?can constructed by targeted deletion of multidrug efflux transporters and calcineurin genes was used for the bioassay. POS was extracted from plasma by protein precipitation with acetonitrile-methanol (75%/25%, vol/vol). Reproducible standard curves were obtained over the range 0.014 to 12 (UPLC-MS/MS) and 0.028 to 12 ?g/ml (bioassay). Intra- and interrun accuracy levels were 106% ± 2% and 103% ± 4% for UPLC-MS/MS and 102% ± 8% and 104% ± 1% for bioassay, respectively. The intra- and interrun coefficients of variation were 7% ± 4% and 7% ± 3% for UPLC-MS/MS and 5% ± 3% and 4% ± 2% for bioassay, respectively. An excellent correlation between POS plasma concentrations measured by UPLC-MS/MS and bioassay was found (concordance, 0.96). In 26 hemato-oncological patients receiving oral POS, 27/69 (39%) trough plasma concentrations were lower than 0.5 ?g/ml. The UPLC-MS/MS method and sensitive bioassay offer alternative tools for accurate and precise quantification of the plasma concentrations in patients receiving oral posaconazole.

Multivariable regression analysis and hot-spot stress approach into fatigue life estimations of welded joints

Kolmen eri hitsausliitoksen väsymisikä arvio on analysoitu monimuuttuja regressio analyysin avulla. Regression perustana on laaja S-N tietokanta joka on kerätty kirjallisuudesta. Tarkastellut liitokset ovat tasalevy liitos, krusiformi liitos ja pitkittäisripa levyssä. Muuttujina ovat jännitysvaihtelu, kuormitetun levyn paksuus ja kuormitus tapa. Paksuus effekti on käsitelty uudelleen kaikkia kolmea liitosta ajatellen. Uudelleen käsittelyn avulla on varmistettu paksuus effektin olemassa olo ennen monimuuttuja regressioon siirtymistä. Lineaariset väsymisikä yhtalöt on ajettu kolmelle hitsausliitokselle ottaen huomioon kuormitetun levyn paksuus sekä kuormitus tapa. Väsymisikä yhtalöitä on verrattu ja keskusteltu testitulosten valossa, jotka on kerätty kirjallisuudesta. Neljä tutkimustaon tehty kerättyjen väsymistestien joukosta ja erilaisia väsymisikä arvio metodeja on käytetty väsymisiän arviointiin. Tuloksia on tarkasteltu ja niistä keskusteltu oikeiden testien valossa. Tutkimuksissa on katsottu 2mm ja 6mm symmetristäpitkittäisripaa levyssä, 12.7mm epäsymmetristä pitkittäisripaa, 38mm symmetristä pitkittäisripaa vääntökuormituksessa ja 25mm/38mm kuorman kantavaa krusiformi liitosta vääntökuormituksessa. Mallinnus on tehty niin lähelle testi liitosta kuin mahdollista. Väsymisikä arviointi metodit sisältävät hot-spot metodin jossa hot-spot jännitys on laskettu kahta lineaarista ja epälineaarista ekstrapolointiakäyttäen sekä paksuuden läpi integrointia käyttäen. Lovijännitys ja murtumismekaniikka metodeja on käytetty krusiformi liitosta laskiessa.

Deep-hole drilling process, monitoring system and sensors modifications

 In the drilling processes and especially deep-hole drilling process, the monitoring system and having control on mechanical parameters (e.g. Force, Torque,Vibration and Acoustic emission) are essential. The main focus of this thesis work is to study the characteristics of deep-hole drilling process, and optimize the monitoring system for controlling the process. The vibration is considered as a major defect area of the deep-hole drilling process which often leads to breakage of the drill, therefore by vibration analysis and optimizing the workpiecefixture, this area is studied by finite element method and the suggestions are explained. By study on a present monitoring system, and searching on the new sensor products, the modifications and recommendations are suggested for optimize the present monitoring system for excellent performance in deep-hole drilling process research and measurements.

Histological description of seminiferous epithelium and cycle length of spermatogenesis in the water shrew Neomys fodiens (Mammalia: Soricidae).

Recently, we examined the spermatogenesis cycle length in two shrews species, Sorex araneus characterized by a very high metabolic rate and a polyandric mating system (sperm competition) resulting in a short cycle and Crocidura russula characterized by a much lower metabolic rate and a monogamous mating system showing a longer cycle. In this study, we investigated the spermatogenesis cycle in Neomys fodiens showing an intermediate metabolic rate. We described the stages of seminiferous epithelium according to the spermatid morphology method and we calculated the cycle length of spermatogenesis using incorporation of 5-bromodeoxyuridine into DNA of the germ cells. Twelve males were injected intraperitoneally with 5-bromodeoxyuridine, and the testes were collected. For cycle length determination, we applied a recently developed statistical method. The calculated cycle length is 8.69 days and the total duration of spermatogenesis based on 4.5 cycles is approximately 39.1 days, intermediate between the duration of spermatogenesis of S. araneus (37.6 days) and C. russula (54.5 days) and therefore congruent with both the metabolic rate hypothesis and the sperm competition hypothesis. Relative testes size of 1.4% of body mass indicates a promiscuous mating system.

Assessing Patient's belief on HIV testing before elective surgery: place for improvements in Switzerland

Background and aim of the study: In Switzerland no HIV test is performed without the patient's consent based on a Voluntary Counseling and Testing policy (VCT). We hypothesized that a substantial proportion of patients going through an elective surgery falsely believed that an HIV test was performed on a routine basis and that the lack of transmission of result was interpreted as being HIV negative. Material and method: All patients with elective orthopedic surgery during 2007 were contacted by phone in 2008. A structured questionnaire assessed their belief about routine preoperative blood analysis (glycemia, coagulation capacity, HIV serology and cholesterol) as well as result awareness and interpretation. Variables included age and gender. Analysis were conducted using the software JMP 6.0.3. Results: 1123 patients were included. 130 (12%) were excluded (i.e. unreachable, unable to communicate on the phone, not operated). 993 completed the survey (89%). Median age was 51 (16-79). 50% were female. 376 (38%) patients thought they had an HIV test performed before surgery but none of them had one. 298 (79%) interpreted the absence of result as a negative HIV test. A predictive factor to believe an HIV test had been done was an age below 50 years old (45% vs 33% for 16-49 years old and 50-79 years old respectively, p <0.001). No difference was observed between genders. Conclusion: In Switzerland, nearly 40% of the patients falsely thought an HIV test had been performed on a routine basis before surgery and were erroneously reassured about their HIV status. These results should either improve the information given to the patient regarding preoperative exams, or motivate public health policy to consider HIV opt-out screening, as patients are already expecting it.

Psykologinen sopimus: työntekijän näkökulma

Työsopimusta solmittaessa syntyy työntekijänja työnantajan välille, kuin huomaamatta myös psykologinen sopimus. Tutkimuksentavoitteena on selvittää millaisia ovat kohdeyrityksen työntekijöiden psykologiset sopimukset, rikotaanko näitä sopimuksia ja kuinka työntekijät reagoivat mahdollisiin rikkomuksiin. Tutkimuksen kohderyhmänä on seitsemän työntekijää, jotka työskentelevät suuressa teollisuusyrityksessä Suomessa. Tutkimuksessa käytetty tutkimusmenetelmä on kvalitatiivinen. Tutkimuksen empiirinen aineisto koostuu teemahaastatteluista. Haastatteluissa pyrittiin selvittämään työntekijöiden psykologisiin sopimuksiin liittyviä käsityksiä, kokemuksia ja tulkintoja. Aineiston analyysissa tulkinta pohjautuu käsitteellisessä osiossa esitettyihin käsitteisiin ja malleihin. Tutkimustulosten mukaan haastateltavien työntekijöiden psykologiset sopimukset ovat hyvin transaktionaalisia. Psykologisia sopimuksia on myös rikottu. Rikkomuksiin haastateltavat ovat reagoineet keskustelemalla työnantajan kanssa tai olemalla vaiti ja sopeutumalla tilanteeseen. Rikkomukset ovat myös vaikuttaneet negatiivisesti haastateltavien työkäyttäytymiseen.

Supporting knowledge creation and sharing in the early phases of the strategic innovation process

The driving forces of technology and globalization continuously transform the business landscape in a way which undermines the existing strategies and innovations of organizations. The challenge for organizations is to establish such conditions where they are able to create new knowledge for innovative business ideas in interaction between other organizations and individuals. Innovation processes continuously need new external stimulations and seek new ideas, new information and knowledge locating more and more outside traditional organizational boundaries. In several studies, the early phases of the innovation process have been considered as the most critical ones. During these phases, the innovation process can emerge or conclude. External knowledge acquirement and utilization are noticed to be important at this stage of the innovation process giving information about the development of future markets and needs for new innovative businessideas. To make it possible, new methods and approaches to manage proactive knowledge creation and sharing activities are needed. In this study, knowledge creation and sharing in the early phases of the innovation process has been studied, and the understanding of knowledge management in the innovation process in an open and collaborative context advanced. Furthermore, the innovation management methods in this study are combined in a novel way to establish an open innovation process and tested in real-life cases. For these purposes two complementary and sequentially applied group work methods - the heuristic scenario method and the idea generation process - are examined by focusing the research on the support of the open knowledge creation and sharing process. The research objective of this thesis concerns two doctrines: the innovation management including the knowledge management, and the futures research concerning the scenario paradigm. This thesis also applies the group decision support system (GDSS) in the idea generation process to utilize the converged knowledge during the scenario process.

Isentropic Exergy and Pressure of the Shock Wave Caused by the Explosion of a Pressure Vessel

An accidental burst of a pressure vessel is an uncontrollable and explosion-like batch process. In this study it is called an explosion. The destructive effectof a pressure vessel explosion is relative to the amount of energy released in it. However, in the field of pressure vessel safety, a mutual understanding concerning the definition of explosion energy has not yet been achieved. In this study the definition of isentropic exergy is presented. Isentropic exergy is the greatest possible destructive energy which can be obtained from a pressure vessel explosion when its state changes in an isentropic way from the initial to the final state. Finally, after the change process, the gas has similar pressure and flow velocity as the environment. Isentropic exergy differs from common exergy inthat the process is assumed to be isentropic and the final gas temperature usually differs from the ambient temperature. The explosion process is so fast that there is no time for the significant heat exchange needed for the common exergy.Therefore an explosion is better characterized by isentropic exergy. Isentropicexergy is a characteristic of a pressure vessel and it is simple to calculate. Isentropic exergy can be defined also for any thermodynamic system, such as the shock wave system developing around an exploding pressure vessel. At the beginning of the explosion process the shock wave system has the same isentropic exergyas the pressure vessel. When the system expands to the environment, its isentropic exergy decreases because of the increase of entropy in the shock wave. The shock wave system contains the pressure vessel gas and a growing amount of ambient gas. The destructive effect of the shock wave on the ambient structures decreases when its distance from the starting point increases. This arises firstly from the fact that the shock wave system is distributed to a larger space. Secondly, the increase of entropy in the shock waves reduces the amount of isentropic exergy. Equations concerning the change of isentropic exergy in shock waves are derived. By means of isentropic exergy and the known flow theories, equations illustrating the pressure of the shock wave as a function of distance are derived. Amethod is proposed as an application of the equations. The method is applicablefor all shapes of pressure vessels in general use, such as spheres, cylinders and tubes. The results of this method are compared to measurements made by various researchers and to accident reports on pressure vessel explosions. The test measurements are found to be analogous with the proposed method and the findings in the accident reports are not controversial to it.

Technology selection and group decision support systems: Case studies on supporting strategic technology selection processes

The objective of the dissertation is to increase understanding and knowledge in the field where group decision support system (GDSS) and technology selection research overlap in the strategic sense. The purpose is to develop pragmatic, unique and competent management practices and processes for strategic technology assessment and selection from the whole company's point of view. The combination of the GDSS and technology selection is approached from the points of view of the core competence concept, the lead user -method, and different technology types. In this research the aim is to find out how the GDSS contributes to the technology selection process, what aspects should be considered when selecting technologies to be developed or acquired, and what advantages and restrictions the GDSS has in the selection processes. These research objectives are discussed on the basis of experiences and findings in real life selection meetings. The research has been mainly carried outwith constructive, case study research methods. The study contributes novel ideas to the present knowledge and prior literature on the GDSS and technology selection arena. Academic and pragmatic research has been conducted in four areas: 1) the potential benefits of the group support system with the lead user -method,where the need assessment process is positioned as information gathering for the selection of wireless technology development projects; 2) integrated technology selection and core competencies management processes both in theory and in practice; 3) potential benefits of the group decision support system in the technology selection processes of different technology types; and 4) linkages between technology selection and R&D project selection in innovative product development networks. New type of knowledge and understanding has been created on the practical utilization of the GDSS in technology selection decisions. The study demonstrates that technology selection requires close cooperation between differentdepartments, functions, and strategic business units in order to gather the best knowledge for the decision making. The GDSS is proved to be an effective way to promote communication and co-operation between the selectors. The constructs developed in this study have been tested in many industry fields, for example in information and communication, forest, telecommunication, metal, software, and miscellaneous industries, as well as in non-profit organizations. The pragmatic results in these organizations are some of the most relevant proofs that confirm the scientific contribution of the study, according to the principles of the constructive research approach.

Fabrication and characterization of silicon position sensitive particle detectors

Position sensitive particle detectors are needed in high energy physics research. This thesis describes the development of fabrication processes and characterization techniques of silicon microstrip detectors used in the work for searching elementary particles in the European center for nuclear research, CERN. The detectors give an electrical signal along the particles trajectory after a collision in the particle accelerator. The trajectories give information about the nature of the particle in the struggle to reveal the structure of the matter and the universe. Detectors made of semiconductors have a better position resolution than conventional wire chamber detectors. Silicon semiconductor is overwhelmingly used as a detector material because of its cheapness and standard usage in integrated circuit industry. After a short spread sheet analysis of the basic building block of radiation detectors, the pn junction, the operation of a silicon radiation detector is discussed in general. The microstrip detector is then introduced and the detailed structure of a double-sided ac-coupled strip detector revealed. The fabrication aspects of strip detectors are discussedstarting from the process development and general principles ending up to the description of the double-sided ac-coupled strip detector process. Recombination and generation lifetime measurements in radiation detectors are discussed shortly. The results of electrical tests, ie. measuring the leakage currents and bias resistors, are displayed. The beam test setups and the results, the signal to noise ratio and the position accuracy, are then described. It was found out in earlier research that a heavy irradiation changes the properties of radiation detectors dramatically. A scanning electron microscope method was developed to measure the electric potential and field inside irradiated detectorsto see how a high radiation fluence changes them. The method and the most important results are discussed shortly.

Mass transfer and particleinteractions in granular systems and suspension flows

The purpose of this study was to investigate some important features of granular flows and suspension flows by computational simulation methods. Granular materials have been considered as an independent state ofmatter because of their complex behaviors. They sometimes behave like a solid, sometimes like a fluid, and sometimes can contain both phases in equilibrium. The computer simulation of dense shear granular flows of monodisperse, spherical particles shows that the collisional model of contacts yields the coexistence of solid and fluid phases while the frictional model represents a uniform flow of fluid phase. However, a comparison between the stress signals from the simulations and experiments revealed that the collisional model would result a proper match with the experimental evidences. Although the effect of gravity is found to beimportant in sedimentation of solid part, the stick-slip behavior associated with the collisional model looks more similar to that of experiments. The mathematical formulations based on the kinetic theory have been derived for the moderatesolid volume fractions with the assumption of the homogeneity of flow. In orderto make some simulations which can provide such an ideal flow, the simulation of unbounded granular shear flows was performed. Therefore, the homogeneous flow properties could be achieved in the moderate solid volume fractions. A new algorithm, namely the nonequilibrium approach was introduced to show the features of self-diffusion in the granular flows. Using this algorithm a one way flow can beextracted from the entire flow, which not only provides a straightforward calculation of self-diffusion coefficient but also can qualitatively determine the deviation of self-diffusion from the linear law at some regions nearby the wall inbounded flows. Anyhow, the average lateral self-diffusion coefficient, which was calculated by the aforementioned method, showed a desirable agreement with thepredictions of kinetic theory formulation. In the continuation of computer simulation of shear granular flows, some numerical and theoretical investigations were carried out on mass transfer and particle interactions in particulate flows. In this context, the boundary element method and its combination with the spectral method using the special capabilities of wavelets have been introduced as theefficient numerical methods to solve the governing equations of mass transfer in particulate flows. A theoretical formulation of fluid dispersivity in suspension flows revealed that the fluid dispersivity depends upon the fluid properties and particle parameters as well as the fluid-particle and particle-particle interactions.

Testing website usability in Spanish-Speaking Academia through heuristic evaluation and cognitive walkthroughs

Although usability evaluations have been focused on assessing different contexts of use, no proper specifications have been addressed towards the particular environment of academic websites in the Spanish-speaking context of use. Considering that this context involves hundreds of millions of potential users, the AIPO Association is running the UsabAIPO Project. The ultimate goal is to promote an adequate translation of international standards, methods and ideal values related to usability in order to adapt them to diverse Spanish-related contexts of use. This article presents the main statistical results coming from the Second and Third Stages of the UsabAIPO Project, where the UsabAIPO Heuristic method (based on Heuristic Evaluation techniques) and seven Cognitive Walkthroughs were performed over 69 university websites. The planning and execution of the UsabAIPO Heuristic method and the Cognitive Walkthroughs, the definition of two usability metrics, as well as the outline of the UsabAIPO Heuristic Management System prototype are also sketched.

Review. Precision viticulture. Research topics, challenges and opportunities in site-specific vineyard management

Precision Viticulture (PV) is a concept that is beginning to have an impact on the wine-growing sector. Its practical implementation is dependant on various technological developments: crop sensors and yield monitors, local and remote sensors, Global Positioning Systems (GPS), VRA (Variable-Rate Application) equipment and machinery, Geographic Information Systems (GIS) and systems for data analysis and interpretation. This paper reviews a number of research lines related to PV. These areas of research have focused on four very specific fields: 1) quantification and evaluation of within-field variability, 2) delineation of zones of differential treatment at parcel level, based on the analysis and interpretation of this variability, 3) development of Variable-Rate Technologies (VRT) and, finally, 4) evaluation of the opportunities for site-specific vineyard management. Research in these fields should allow winegrowers and enologists to know and understand why yield variability exists within the same parcel, what the causes of this variability are, how the yield and its quality are interrelated and, if spatial variability exists, whether site-specific vineyard management is justifiable on a technical and economic basis.

A Large-Sized Multiwire Proportional Counter for Radiological Survey of Large Areas and Surfaces

Työn tavoitteena oli selvittää, miten eri parametrit vaikuttavat monilankaisen verrannollisuuslaskurin laskennallisiin ominaisuuksiin sekä voidaanko suurikokoista monilankaverrannollisuuslaskuria käyttää tehokkaasti suurien pintojen ? - ja ?- kontaminaation mittaamiseen. Ensin selvitettiin EU:n nykyistä clearing-käytäntöä sekä hahmoteltiin tulevia materiaalivirtoja, esiteltiin verrannollisuuslaskurin ja sen monilankamallin toimintaperiaate sekä käytettävien materiaalien ominaisuudet. Kootun teorian pohjalta selvitettiin tärkeimpien parametrien vaikutus ilmaisimen laskennallisiin ominaisuuksiin. Lopuksi suoritettiin rakenteilla olevan monilankaverrannollisuuslaskurin alustava testaus. Tulevien vuosien aikana eri puolilla maailmaa suljettavat erityyppiset ydinlaitokset luovat suuren tarpeen tehokkaiden kontaminaatiomittauslaitteistojen kehittämiselle. Tällä hetkellä mittaukset suoritetaan lähinnä noin 1 dm2 käsi-instrumentein, joten suurikokoinen, automatisoitu mittauslaitteisto sekä tehostaisi mittausprosessia suuresti sekä säästäisi runsaasti miestyötunteja. Jatkotoimenpiteiksi ehdotetaan laitteiston jatkotestausta, liikkeen ja nopeuden testausta sekä lopulta paikkaherkkyystoiminnon toteuttamisperiaatteen valintaa ja testausta.

Validity of the FACIT-Sp to assess spiritual well-being in elderly patients

Among instruments measuring spiritual well-being, the Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp-12) is the most widely used instrument in research. It has been validated in patients suffering from cancer or HIV/AIDS, but has rarely been used in elderly patients. The objectives of this study were to determine the psychometric properties and suitability of the FACIT-Spto assess spiritual well-being in hospitalized elderly patients. This cross-sectional study uses a mixed method approach. Subjects were patients (N = 208), aged 65 years and older, consecutively admitted in post-acute rehabilitation. Psychometric properties of the FACITSp were investigated. The internal structure of the FACIT-Sp (factor structure and internal consistency) was assessed. Convergent validity of the FACIT-Sp was assessed using the Spiritual Distress Assessment Tool (SDAT), the question "Are you at peace?" and the Geriatric Depression Scale (GDS). Predictive validity was assessed using length of stay (LOS) and discharge destination. Understanding and interpretation of FACIT-Sp items were consecutively assessed in a sub-sample of 135 patients. Results show that FACIT-Sp scores ranged from 7 to 46 (mean 29.6 ± 7.8); 23.1% of the patients had high spiritual well-being. Cronbach's α was g ood ( 0.85). Item-to-total correlations were all significant (0.34 to 0.73). Principal component analyses performed with 2 or 3 factors were only moderately consistent with previous work. FACIT-Sp correlated with SDAT, "Are you at peace?" and GDS (Rho = −0.45, P < 0.001; 0.51, P < 0.001 and −0.38, P < 0.001). No association was found with LOS or discharge destination. Spontaneous comments about one or more FACIT-Sp items were made by 97/135 (71.9%). Specifically, items that address purpose and meaning in life were frequently found difficult to answer. Analyses suggest that the FACIT-Sp may underestimate spiritual well-being in older patients. In conclusion, despite having acceptable psychometric properties, the FACIT-Sp presents limitations for measurement of spiritual well-being in hospitalized elderly patients.