Accurate mass-based analysis in human sport doping control : Application of liquid chromatography - time-of-flight mass spectrometry

Human sport doping control analysis is a complex and challenging task for anti-doping laboratories. The List of Prohibited Substances and Methods, updated annually by World Anti-Doping Agency (WADA), consists of hundreds of chemically and pharmacologically different low and high molecular weight compounds. This poses a considerable challenge for laboratories to analyze for them all in a limited amount of time from a limited sample aliquot. The continuous expansion of the Prohibited List obliges laboratories to keep their analytical methods updated and to research new available methodologies. In this thesis, an accurate mass-based analysis employing liquid chromatography - time-of-flight mass spectrometry (LC-TOFMS) was developed and validated to improve the power of doping control analysis. New analytical methods were developed utilizing the high mass accuracy and high information content obtained by TOFMS to generate comprehensive and generic screening procedures. The suitability of LC-TOFMS for comprehensive screening was demonstrated for the first time in the field with mass accuracies better than 1 mDa. Further attention was given to generic sample preparation, an essential part of screening analysis, to rationalize the whole work flow and minimize the need for several separate sample preparation methods. Utilizing both positive and negative ionization allowed the detection of almost 200 prohibited substances. Automatic data processing produced a Microsoft Excel based report highlighting the entries fulfilling the criteria of the reverse data base search (retention time (RT), mass accuracy, isotope match). The quantitative performance of LC-TOFMS was demonstrated with morphine, codeine and their intact glucuronide conjugates. After a straightforward sample preparation the compounds were analyzed directly without the need for hydrolysis, solvent transfer, evaporation or reconstitution. The hydrophilic interaction technique (HILIC) provided good chromatographic separation, which was critical for the morphine glucuronide isomers. A wide linear range (50-5000 ng/ml) with good precision (RSD<10%) and accuracy (±10%) was obtained, showing comparable or better performance to other methods used. In-source collision-induced dissociation (ISCID) allowed confirmation analysis with three diagnostic ions with a median mass accuracy of 1.08 mDa and repeatable ion ratios fulfilling WADA s identification criteria. The suitability of LC-TOFMS for screening of high molecular weight doping agents was demonstrated with plasma volume expanders (PVE), namely dextran and hydroxyethylstarch (HES). Specificity of the assay was improved, since interfering matrix compounds were removed by size exclusion chromatography (SEC). ISCID produced three characteristic ions with an excellent mean mass accuracy of 0.82 mDa at physiological concentration levels. In summary, by combining TOFMS with a proper sample preparation and chromatographic separation, the technique can be utilized extensively in doping control laboratories for comprehensive screening of chemically different low and high molecular weight compounds, for quantification of threshold substances and even for confirmation. LC-TOFMS rationalized the work flow in doping control laboratories by simplifying the screening scheme, expediting reporting and minimizing the analysis costs. Therefore LC-TOFMS can be exploited widely in doping control, and the need for several separate analysis techniques is reduced.

Löydöstä muinaispuvuksi : arkeologisten tekstiilien ennallistaminen

From a find to an ancient costume - reconstruction of archaeological textiles Costume tells who we are. It warms and protects us, but also tells about our identity: gender, age, family, social group, work, religion and ethnicity. Textile fabrication, use and trade have been an important part of human civilization for more than 10 000 years. There are plenty of archaeological textile findings, but they are small, fragmentary and their interpretation requires special skills. Finnish textile findings from the younger Iron Age have already been studied for more than hundred years. They have also been used as a base for several reconstructions called muinaispuku , ancient costume. Thesis surveys the ancient costume reconstruction done in Finland and discusses the objectives of the reconstruction projects. The earlier reconstruction projects are seen as a part of the national project of constructing a glorious past for Finnish nationality, and the part women took in this project. Many earlier reconstructions are designed to be festive costumes for wealthy ladies. In the 1980s and 1990s many new ancient costume reconstructions were made, differing from their predecessors at the pattern of the skirt. They were also done following the principles of making a scientific reconstruction more closely. At the same time historical re-enactment and living history as a hobby have raised in popularity, and the use of ancient costumes is widening from festive occasions to re-enactment purposes. A hypothesis of the textile craft methods used in younger Iron Age Finland is introduced. Archaeological findings from Finland and neighboring countries, ethnological knowledge of textile crafts and experimental archaeology have been used as a basis for this proposition. The yarn was spinned with a spindle, the fabrics woven on a warp-weighted loom and dyed with natural colors. Bronze spiral applications and complicated tablet-woven bands have possibly been done by specialist craftswomen or -men. The knowledge of the techniques and results of experimenting and experimental archaeology gives a possibility to review the success of existing ancient costume reconstructions as scientific reconstructions. Only one costume reconstruction project, the Kaarina costume fabricated in Kurala Kylämäki museum, has been done using as authentic methods as possible. The use of ancient craft methods is time-consuming and expensive. This fact can be seen as one research result itself for it demonstrates how valuable the ancient textiles have been also in their time of use. In the costume reconstruction work, the skill of a craftswoman and her knowledge of ancient working methods is strongly underlined. Textile research is seen as a process, where examination of original textiles and reconstruction experiments discuss with each other. Reconstruction projects can give a lot both to the research of Finnish younger Iron Age and the popularization of archaeological knowledge. The reconstruction is never finished, and also the earlier reconstructions should be reviewed in the light of new findings.

Effect of waiting time on health outcomes and service utilization : A prospective randomized study on patients admitted to hospital for hip or knee replacement

Although the principle of equal access to medically justified treatment has been promoted by official health policies in many Western health care systems, practices do not completely meet policy targets. Waiting times for elective surgery vary between patient groups and regions, and growing problems in the availability of services threaten equal access to treatment. Waiting times have come to the attention of decision-makers, and several policy initiatives have been introduced to ensure the availability of care within a reasonable time. In Finland, for example, the treatment guarantee came into force in 2005. However, no consensus exists on optimal waiting time for different patient groups. The purpose of this multi-centre randomized controlled trial was to analyse health-related quality of life, pain and physical function in total hip or knee replacement patients during the waiting time and to evaluate whether the waiting time is associated with patients health outcomes at admission. This study also assessed whether the length of waiting time is associated with social and health services utilization in patients awaiting total hip or knee replacement. In addition, patients health-related quality of life was compared with that of the general population. Consecutive patients with a need for a primary total hip or knee replacement due to osteoarthritis were placed on the waiting list between August 2002 and November 2003. Patients were randomly assigned to a short waiting time (maximum 3 months) or a non-fixed waiting time (waiting time not fixed in advance, instead the patient followed the hospitals routine practice). Patients health-related quality of life was measured upon being placed on the waiting list and again at hospital admission using the generic 15D instrument. Pain and physical function were evaluated using the self-report Harris Hip Score for hip patients and a scale modified from the Knee Society Clinical Rating System for knee patients. Utilization measures were the use of home health care, rehabilitation and social services, physician visits and inpatient care. Health and social services use was low in both waiting time groups. The most common services used while waiting were rehabilitation services and informal care, including unpaid care provided by relatives, neighbours and volunteers. Although patients suffered from clear restrictions in usual activities and physical functioning, they seemed primarily to lean on informal care and personal networks instead of professional care. While longer waiting time did not result in poorer health-related quality of life at admission and use of services during the waiting time was similar to that at the time of placement on the list, there is likely to be higher costs of waiting by people who wait longer simply because they are using services for a longer period. In economic terms, this would represent a negative impact of waiting. Only a few reports have been published of the health-related quality of life of patients awaiting total hip or knee replacement. These findings demonstrate that, in addition to physical dimensions of health, patients suffered from restrictions in psychological well-being such as depression, distress and reduced vitality. This raises the question of how to support patients who suffer from psychological distress during the waiting time and how to develop strategies to improve patients initiatives to reduce symptoms and the burden of waiting. Key words: waiting time, total hip replacement, total knee replacement, health-related quality of life, randomized controlled trial, outcome assessment, social service, utilization of health services

Geological factors affecting on after-use of Finnish cut-over peatlands : with implications on the carbon accumulation

In Finland, peat harvesting sites are utilized down almost to the mineral soil. In this situation the properties of mineral subsoil are likely to have considerable influence on the suitability for the various after-use forms. The aims of this study were to recognize the chemical and physical properties of mineral subsoils possibly limiting the after-use of cut-over peatlands, to define a minimum practice for mineral subsoil studies and to describe the role of different geological areas. The future percentages of the different after-use forms were predicted, which made it possible to predict also carbon accumulation in this future situation. Mineral subsoils of 54 different peat production areas were studied. Their general features and grain size distribution was analysed. Other general items studied were pH, electrical conductivity, organic matter, water soluble nutrients (P, NO3-N, NH4-N, S and Fe) and exchangeable nutrients (Ca, Mg and K). In some cases also other elements were analysed. In an additional case study carbon accumulation effectiveness before the intervention was evaluated on three sites in Oulu area (representing sites typically considered for peat production). Areas with relatively sulphur rich mineral subsoil and pool-forming areas with very fine and compact mineral subsoil together covered approximately 1/5 of all areas. These areas were unsuitable for commercial use. They were recommended for example for mire regeneration. Another approximate 1/5 of the areas included very coarse or very fine sediments. Commercial use of these areas would demand special techniques - like using the remaining peat layer for compensating properties missing from the mineral subsoil. One after-use form was seldom suitable for one whole released peat production area. Three typical distribution patterns (models) of different mineral subsoils within individual peatlands were found. 57 % of studied cut-over peatlands were well suited for forestry. In a conservative calculation 26% of the areas were clearly suitable for agriculture, horticulture or energy crop production. If till without large boulders was included, the percentage of areas suitable to field crop production would be 42 %. 9-14 % of all areas were well suitable for mire regeneration or bird sanctuaries, but all areas were considered possible for mire regeneration with correct techniques. Also another 11 % was recommended for mire regeneration to avoid disturbing the mineral subsoil, so total 20-25 % of the areas would be used for rewetting. High sulphur concentrations and acidity were typical to the areas below the highest shoreline of the ancient Litorina sea and Lake Ladoga Bothnian Bay zone. Also differences related to nutrition were detected. In coarse sediments natural nutrient concentration was clearly higher in Lake Ladoga Bothnian Bay zone and in the areas of Svecokarelian schists and gneisses, than in Granitoid area of central Finland and in Archaean gneiss areas. Based on this study the recommended minimum analysis for after-use planning was for pH, sulphur content and fine material (<0.06 mm) percentage. Nutrition capacity could be analysed using the natural concentrations of calcium, magnesium and potassium. Carbon accumulation scenarios were developed based on the land-use predictions. These scenarios were calculated for areas in peat production and the areas released from peat production (59300 ha + 15 671 ha). Carbon accumulation of the scenarios varied between 0.074 and 0.152 million t C a-1. In the three peatlands considered for peat production the long term carbon accumulation rates varied between 13 and 24 g C m-2 a-1. The natural annual carbon accumulation had been decreasing towards the time of possible intervention.

Use of Customer Information: An Ethnography in Service Development

Service researchers have repeatedly claimed that firms should acquire customer information in order to develop services that fit customer needs. Despite this, studies that would concentrate on the actual use of customer information in service development are lacking. The present study fulfils this research gap by investigating information use during a service development process. It demonstrates that use is not a straightforward task that automatically follows the acquisition of customer information. In fact, out of the six identified types of use, four represent non usage of customer information. Hence, the study demonstrates that the acquisition of customer information does not guarantee that the information will actually be used in development. The current study used an ethnographic approach. Consequently, the study was conducted in the field in real time over an extensive period of 13 months. Participant observation allowed direct access to the investigated phenomenon, i.e. the different types of use by the observed development project members were captured while they emerged. In addition, interviews, informal discussions and internal documents were used to gather data. A development process of a bank’s website constituted the empirical context of the investigation. This ethnography brings novel insights to both academia and practice. It critically questions the traditional focus on the firm’s acquisition of customer information and suggests that this focus ought to be expanded to the actual use of customer information. What is the point in acquiring costly customer information if it is not used in the development? Based on the findings of this study, a holistic view on customer information, “information in use” is generated. This view extends the traditional view of customer information in three ways: the source, timing and form of data collection. First, the study showed that the customer information can come explicitly from the customer, from speculation among the developers or it can already exist implicitly. Prior research has mainly focused on the customer as the information provider and the explicit source to turn to for information. Second, the study identified that the used and non-used customer information was acquired both previously, and currently within the time frame of the focal development process, as well as potentially in the future. Prior research has primarily focused on the currently acquired customer information, i.e. within the timeframe of the development process. Third, the used and non-used customer information was both formally and informally acquired. In prior research a large number of sophisticated formal methods have been suggested for the acquisition of customer information to be used in development. By focusing on “information in use”, new knowledge on types of customer information that are actually used was generated. For example, the findings show that the formal customer information acquired during the development process is used less than customer information already existent within the firm. With this knowledge at hand, better methods to capture this more usable customer information can be developed. Moreover, the thesis suggests that by focusing stronger on use of customer information, service development processes can be restructured in order to facilitate the information that is actually used.