Female pelvic floor disorders – outcome after mesh-augmented procedures and studies on vaginal connective tissue

Pelvic floor disorders, such as urinary incontinence (UI) and pelvic organ prolapse (POP), are common disorders in women. Because of the prolonged life expectancy the prevalence of UI and POP and the probability of ending up in surgery are increasing. However, the pathophysiology behind these disorders is still unsolved. The aim of this thesis is to study possible alterations in the connective tissue in the vaginal wall in patients with and without POP. The long-term outcome and complications of mid-urethral slings (MUS) and mesh-augmented POP surgery were studied in heterogenic patient populations. More elastin and a slight increase in immunostaining of type III and V collagens in tissue samples were obtained from patients with POP compared to controls in whom type I collagen was more prominent. The studies assessing the mesh-augmented procedures revealed good efficacy and high patient satisfaction after a long-term follow-up. Patients operated on because of mixed incontinence and with BMI >30 kg/m² reported significantly more urinary symptoms and a lower quality of life than the patients operated on because of stress urinary incontinence and the ones with BMI ≤30 kg/m². The objective outcome was equal between the groups. Mesh exposure through vaginal mucosa occurred in 23 % of the patients after POP surgery, most of these being asymptomatic. There are alterations in connective tissues in patients with POP. Mid-urethral sling procedures produced good long-term cure rates and patient satisfaction. As to the prolapse surgery, in spite of relatively high exposure rate, mesh-augmented procedure proved to be safe and effective method for the correction of POP.

Kahden kulttuurin ääniä

Opinnäytetyöni Kahden kulttuurin ääniä on monimuototyö, jonka teososa koostuu kuudesta suunnittelemastani ja äänittämästäni konkreettisen musiikin teoksesta. Materiaali on äänitetty 2006 kesällä ja syksyllä Suomessa ja Japanissa. Kirjallisessa osassa tarkastelin lajityypin historiaa sekä omaan työskentelyyni peilaten keinoja, joilla tein kenttä-äänistä musiikillisen teoksen jaettuna kolmeen eri teemaan kunkin maan äänimateriaalista: luontoäänet, kaupunkiäänet sekä uskonnollisten palvelusten äänet. Teoksille ei tehty ennakkokäsikirjoitusta, vaan niiden kokoaminen tapahtui konkreettisen musiikin perinteiden mukaisesti vasta äänityöasemalla. Työ koostettiin ja miksattiin stereona ja surroundina (5.0) Pro Toolsissa vuoden 2007 aikana. Osa äänimateriaalista säilyi käsittelemättömänä, osa käsiteltiin lähes tunnistamattomaksi. Kahden kulttuurin ääniä poikkeaa lajityypin klassikoista nopealla tempollaan ja runsaalla tunnelmien vaihtelevuudellaan. Toisinaan työ lähentelee jo nykyaikaisia elektronisen musiikin alalajeja. Teokset sisältävät paljon elementtejä, jotka aiheuttavat eri ihmisissä erilaisia assosiaatioita. Tämän vuoksi konkreettinen musiikki voisi hyvin toimia muun muassa musiikkiterapian välineenä.

Role of human hydroxysteroid (17beta) dehydrogenase type 1 (HSD17B1) in steroid-dependent diseases in females –novel indications for HSD17B1 inhibitors. Phenotypic analysis of transgenic mice overexpressing human HSD17B1.

Hormone-dependent diseases, e.g. cancers, rank high in mortality in the modern world, and thus, there is an urgent need for new drugs to treat these diseases. Although the diseases are clearly hormone-dependent, changes in circulating hormone concentrations do not explain all the pathological processes observed in the diseased tissues. A more inclusive explanation is provided by intracrinology – a regulation of hormone concentrations at the target tissue level. This is mediated by the expression of a pattern of steroid-activating and -inactivating enzymes in steroid target tissues, thus enabling a concentration gradient between the blood circulation and the tissue. Hydroxysteroid (17beta) dehydrogenases (HSD17Bs) form a family of enzymes that catalyze the conversion between low active 17-ketosteroids and highly active 17beta-hydroxysteroids. HSD17B1 converts low active estrogen (E1) to highly active estradiol (E2) with high catalytic efficiency, and altered HSD17B1 expression has been associated with several hormone-dependent diseases, including breast cancer, endometriosis, endometrial hyperplasia and cancer, and ovarian epithelial cancer. Because of its putative role in E2 biosynthesis in ovaries and peripheral target tissues, HSD17B1 is considered to be a promising drug target for estrogen-dependent diseases. A few studies have indicated that the enzyme also has androgenic activity, but they have been ignored. In the present study, transgenic mice overexpressing human HSD17B1 (HSD17B1TG mice) were used to study the effects of the enzyme in vivo. Firstly, the substrate specificity of human HSD17B1 was determined in vivo. The results indicated that human HSD17B1 has significant androgenic activity in female mice in vivo, which resulted in increased fetal testosterone concentration and female disorder of sexual development appearing as masculinized phenotype (increased anogenital distance, lack of nipples, lack of vaginal opening, combination of vagina with urethra, enlarged Wolffian duct remnants in the mesovarium and enlarged female prostate). Fetal androgen exposure has been linked to polycystic ovary syndrome (PCOS) and metabolic syndrome during adulthood in experimental animals and humans, but the genes involved in PCOS are largely unknown. A putative mechanism to accumulate androgens during fetal life by HSD17B1 overexpression was shown in the present study. Furthermore, as a result of prenatal androgen exposure locally in the ovaries, HSD17B1TG females developed ovarian benign serous cystadenomas in adulthood. These benign lesions are precursors of low-grade ovarian serous tumors. Ovarian cancer ranks fifth in mortality of all female cancers in Finland, and most of the ovarian cancers arise from the surface epithelium. The formation of the lesions was prevented by prenatal antiandrogen treatment and by transplanting wild type (WT) ovaries prepubertally into HSD17B1TG females. The results obtained in our non-clinical TG mouse model, together with a literature analysis, suggest that HSD17B1 has a role in ovarian epithelial carcinogenesis, and especially in the development of serous tumors. The role of androgens in ovarian carcinogenesis is considered controversial, but the present study provides further evidence for the androgen hypothesis. Moreover, it directly links HSD17B1-induced prenatal androgen exposure to ovarian epithelial carcinogenesis in mice. As expected, significant estrogenic activity was also detected for human HSD17B1. HSD17B1TG mice had enhanced peripheral conversion of E1 to E2 in a variety of target tissues, including the uterus. Furthermore, this activity was significantly decreased by treatments with specific HSD17B1 inhibitors. As a result, several estrogen-dependent disorders were found in HSD17B1TG females. Here we report that HSD17B1TG mice invariably developed endometrial hyperplasia and failed to ovulate in adulthood. As in humans, endometrial hyperplasia in HSD17B1TG females was reversible upon ovulation induction, triggering a rise in circulating progesterone levels, and in response to exogenous progestins. Remarkably, treatment with a HSD17B1 inhibitor failed to restore ovulation, yet completely reversed the hyperplastic morphology of epithelial cells in the glandular compartment. We also demonstrate that HSD17B1 is expressed in normal human endometrium, hyperplasia, and cancer. Collectively, our non-clinical data and literature analysis suggest that HSD17B1 inhibition could be one of several possible approaches to decrease endometrial estrogen production in endometrial hyperplasia and cancer. HSD17B1 expression has been found in bones of humans and rats. The non-clinical data in the present study suggest that human HSD17B1 is likely to have an important role in the regulation of bone formation, strength and length during reproductive years in female mice. Bone density in HSD17B1TG females was highly increased in femurs, but in lesser amounts also in tibias. Especially the tibia growth plate, but not other regions of bone, was susceptible to respond to HSD17B1 inhibition by increasing bone length, whereas the inhibitors did not affect bone density. Therefore, HSD17B1 inhibitors could be safer than aromatase inhibitors in regard to bone in the treatment of breast cancer and endometriosis. Furthermore, diseases related to improper growth, are a promising new indication for HSD17B1 inhibitors.

The Influence of spanish vihuela and lute music on the development of early seventeenth century english keyboard music as exemplified in the Fitzwilliam virginal book

Digitoitu 29.10 2008.

Algorithmic Solutions for Combinatorial Problems in Resource Management of Manufacturing Environments

This thesis studies the use of heuristic algorithms in a number of combinatorial problems that occur in various resource constrained environments. Such problems occur, for example, in manufacturing, where a restricted number of resources (tools, machines, feeder slots) are needed to perform some operations. Many of these problems turn out to be computationally intractable, and heuristic algorithms are used to provide efficient, yet sub-optimal solutions. The main goal of the present study is to build upon existing methods to create new heuristics that provide improved solutions for some of these problems. All of these problems occur in practice, and one of the motivations of our study was the request for improvements from industrial sources. We approach three different resource constrained problems. The first is the tool switching and loading problem, and occurs especially in the assembly of printed circuit boards. This problem has to be solved when an efficient, yet small primary storage is used to access resources (tools) from a less efficient (but unlimited) secondary storage area. We study various forms of the problem and provide improved heuristics for its solution. Second, the nozzle assignment problem is concerned with selecting a suitable set of vacuum nozzles for the arms of a robotic assembly machine. It turns out that this is a specialized formulation of the MINMAX resource allocation formulation of the apportionment problem and it can be solved efficiently and optimally. We construct an exact algorithm specialized for the nozzle selection and provide a proof of its optimality. Third, the problem of feeder assignment and component tape construction occurs when electronic components are inserted and certain component types cause tape movement delays that can significantly impact the efficiency of printed circuit board assembly. Here, careful selection of component slots in the feeder improves the tape movement speed. We provide a formal proof that this problem is of the same complexity as the turnpike problem (a well studied geometric optimization problem), and provide a heuristic algorithm for this problem.

Spectrometrical Monitoring of Laser Sintering Process of Ceramic Material

This thesis is done as a part of project called FuncMama that is a project between Technical Research Centre of Finland (VTT), Oulu University (OY), Lappeenranta University of Technology (LUT) and Finnish industrial partners. Main goal of the project is to manufacture electric and mechanical components from mixed materials using laser sintering. Aim of this study was to create laser sintered pieces from ceramic material and monitor the sintering event by using spectrometer. Spectrometer is a device which is capable to record intensity of different wavelengths in relation with time. In this study the monitoring of laser sintering was captured with the equipment which consists of Ocean Optics spectrometer, optical fiber and optical lens (detector head). Light from the sintering process hit first to the lens system which guides the light in to the optical fibre. Optical fibre transmits the light from the sintering process to the spectrometer where wavelengths intensity level information is detected. The optical lens of the spectrometer was rigidly set and did not move along with the laser beam. Data which was collected with spectrometer from the laser sintering process was converted with Excel spreadsheet program for result’s evaluation. Laser equipment used was IPG Photonics pulse fibre laser. Laser parameters were kept mainly constant during experimental part and only sintering speed was changed. That way it was possible to find differences in the monitoring results without fear of too many parameters mixing together and affecting to the conclusions. Parts which were sintered had one layer and size of 5 x 5 mm. Material was CT2000 – tape manufactured by Heraeus which was later on post processed to powder. Monitoring of different sintering speeds was tested by using CT2000 reference powder. Moreover tests how different materials effect to the process monitoring were done by adding foreign powder Du Pont 951 which had suffered in re-grinding and which was more reactive than CT2000. By adding foreign material it simulates situation where two materials are accidently mixed together and it was studied if that can be seen with the spectrometer. It was concluded in this study that with the spectrometer it is possible to detect changes between different laser sintering speeds. When the sintering speed is lowered the intensity level of light is higher from the process. This is a result of higher temperature at the sintering spot and that can be noticed with the spectrometer. That indicates it could be possible to use spectrometer as a tool for process observation and support the idea of having system that can help setting up the process parameter window. Also important conclusion was how well the adding of foreign material could be seen with the spectrometer. When second material was added a significant intensity level raise could be noticed in that part where foreign material was mixed. That indicates it is possible to see if there are any variations in the material or if there are more materials mixed together. Spectrometric monitoring of laser sintering could be useful tool for process window observation and temperature controlling of the sintering process. For example if the process window for specific material is experimentally determined to get wanted properties and satisfying sintering speed. It is possible if the data is constantly recorded that the results can show faults in the part texture between layers. Changes between the monitoring data and the experimentally determined values can then indicate changes in the material being generated by material faults or by wrong process parameters. The results of this study show that spectrometer could be one possible tool for monitoring. But to get in that point where this all can be made possible much more researching is needed.

Teippaaminen ja liimaaminen teräsrakenteissa

Mekaanisten liittämismenetelmien ja hitsaamisen lisäksi teippaamista ja liimaamista voidaan käyttää myös teräsrakenteissa. Sillä on omat hyvät ja huonot puolensa, joita tässä työssä käydään erilaisten teippien ja liimojen sovelluskohteita tarkastelemalla. Työn tavoitteena on tutkia yleisesti teippejä ja liimoja. Lisäksi työssä on tarkoitus selvittää, soveltuuko liima- tai teippiliitos teollisuusnosturin kaapelikourun liittämiseksi kuormapalkin uumaan.

Cesarean section - short term maternal complications related to the mode of delivery

Cesarean section (CS) is the most common major surgery performed on women worldwide. CS can save the life of the mother or the fetus, but is associated with the typical complications of any major surgery: hemorrhage, infection, venous thromboembolism and complications of anesthesia, sometimes leading to maternal death. Recently there have been several reports from well resourced countries on increased severe maternal morbidity and even mortality. Increased rates of CS, obesity and older mothers may explain this rise. The aim of this thesis is to study the rates and risk factors of short term maternal complications associated with CS. Also, we compared maternal morbidity by mode of delivery and over time. The complication rates were assessed in a prospective study involving 2496 CS performed in the 12 largest delivery units in Finland in 2005. The rates of severe complications were studied by mode of delivery in a register-based study comparing national cohorts in 1997 and 2002. The impact of several risk factors on severe maternal morbidity by mode of delivery was studied in a register-based study of all singleton deliveries in 2007-2011. In the prospective study, 27% of the women who underwent CS had one or more intraoperative or postoperative complications during their hospital stay, and 10% had a severe complication. In the register-based study the incidence of life-threatening maternal complications was 7.6 in 1000 deliveries. The incidence was lowest for vaginal delivery (VD), followed by instrumental VD and elective CS, and highest in emergency CS. An attempt of VD, including the risks associated with emergency CS, seems to be the safest mode of delivery, even for most high-risk women.

Sinkityslinjan pesuosan optimointi

Työn tavoitteena oli sinkityslinjan pesuosan toiminnan optimointi. Teoriakatsauksen ja haastattelututkimusten avulla työssä selvitettiin, mitkä tekijät pesuosalla tai teräsnauhan pesua edeltävissä prosessivaiheissa vaikuttavat pesutehoon alentavasti. Pesuosan ajoparametrien muutoskokeiden avulla määritettiin kunkin pesuparametrin suhteellinen vaikutus pesutulokseen sekä pesuosan optimaaliset ajoparametrit. Vaikutuksia arvioitiin pinnanpuhtauden ja pesuvesien laboratorioanalyysien sekä prosessidatan avulla. Jätevesianalyysien ja prosessidatan avulla arvioitiin lisäksi pesuosan muutosten vaikutusta pesusta syntyviä jätevesiä käsittelevän jätevesilaitoksen toimintaan. Laitetestauksen avulla työssä kartoitettiin, mikä menetelmä pinnanpuhtauden määrittämiseen soveltuu pesuosalle parhaiten. Kustannusarvioinnilla selvitettiin, millä toimin pesuosan toimintavarmuutta on edullisinta ylläpitää. Työn tulosten pohjalta lämpötilalla todettiin olevan pesutuloksen kannalta merkittävin vaikutus. Sen sijaan kemikaaliannostelun merkitys oli vähäinen. Vesien säännöllisen uudistamisen todettiin olevan olennainen pesuvesien ylläpitokeino nykyisessä pesutilanteessa. Se todettiin lisäksi ennakoivana toimenpiteenä kannattavammaksi kuin pesuosan täystyhjäykset ongelmatilanteissa. Teippitestein määritettävälle pinnanpuhtaudelle katsottiin sopivaksi vaihteluväliksi 40–75 %. Työssä todettiin, että pesua edeltävän kylmävalssin valssiöljyn vaihto sekä valssilla tuotetun teräsnauhan pinnanpuhtaus vaikuttavat merkittävästi pesuosan toimintakykyyn ja pesuosan pyörittämisestä aiheutuviin kustannuksiin. Toimenpiteet pesuosalla vaikuttavat lisäksi jätevesilaitoksen käsittelyvaatimuksiin, joskin myös tasaavat sen toimintaa. Työssä ehdotettiin ratkaisukeinoja pesuosan toimintavarmuuden varmistamiseksi jatkossa, sekä tarjottiin työkaluja, joiden avulla tulevissa investointipäätöksissä voidaan ottaa huomioon myös pesuosan toiminnan edellytykset.

Synnytyksen ponnistusvaiheen hoidon käytännöt. Yhteys ensisynnyttäjän välilihan kuntoon synnytyksen jälkeen, synnytyskokemukseen, kipuun ja seksuaaliterveyteen

Hyvän syntymän hoidon tavoitteena on turvata synnyttäjän paras mahdollinen terveys, vähentää tarpeetonta puuttumista synnytyksen kulkuun ja mahdollistaa voimaannuttava synnytyskokemus perheelle. Hyvä syntymän hoito ja siihen liittyvä kätilöiden kliinisen hoitotyön osaaminen ei voi kehittyä, ellei hoitotyön käytäntöjä tutkita. Suomalaista hoitotieteellistä syntymän hoitoon liittyvää tutkimusta on vähän. Tämän tutkimuksen tarkoituksena oli kuvata synnytyksen ponnistusvaiheen hoidon käytäntöjä Suomen synnytyssairaaloissa. Lisäksi seurantatutkimuksen avulla selvitettiin, miten ensisynnyttäjät kokivat synnytyksen ponnistusvaiheen, sen aikana saamansa hoidon, ensisynnyttäjien synnytyskokemusta, kivun kokemista, vointia kolmena päivänä synnytyksen jälkeen sekä heidän seksuaaliterveyttään ensimmäisen vuoden aikana synnytyksen jälkeen. Tutkimuksen tavoitteena oli tuottaa tietoa, jonka avulla voidaan kehittää synnytyksen ponnistusvaiheen hoitoa ja lisätä tietoa synnyttäneiden naisten voinnista ja seksuaaliterveydestä. Tutkimuksen ensimmäinen osio toteutettiin poikkileikkaustutkimuksena (2009), johon osallistui Suomen synnytyssairaaloiden synnytysosastoilla työskentelevät kätilöt (N = 662). Tutkimuksen toinen osio toteutettiin seurantatutkimuksena (2009−2011), jossa oli neljä mittausajankohtaa: kolmantena päivänä synnytyksestä sekä kolmen, kuuden ja kahdentoista kuukauden kuluttua synnytyksestä. Tähän osioon osallistui spontaanisti alateitse yhden elävän lapsen (pää tarjoutuvana) synnyttäneet ensisynnyttäjät (N = 453) ja sikiön perätilan vuoksi suunnitellusti keisarileikatut ensisynnyttäjät (N = 84). Aineisto analysoitiin tilastollisin menetelmin. Tutkimustulosten mukaan osa kätilöiden käyttämistä synnytyksen ponnistusvaiheen hoitokäytännöistä ei ole näyttöön perustuvia. Synnytyssairaalan synnytyksen hoidon kulttuuri näyttää siirtyvän mallioppimisen kautta. Ensisynnyttäjät kokivat synnytyksen ponnistusvaiheen hoidon pääsääntöisesti myönteisenä. Alateitse synnyttäneillä ensisynnyttäjillä oli myönteisempi synnytyskokemus ja vähemmän kipua heti synnytyksen jälkeen ja kolmena synnytyksen jälkeisenä päivänä verrattuna keisarileikkauksella synnyttäneisiin ensisynnyttäjiin. Alateitse synnyttäneillä ensisynnyttäjillä kipu ja ompeleet eivät vaikuttaneet haitallisesti vastasyntyneen hoitoon tai imetykseen niin paljon kuin keisarileikkauksella synnyttäneillä ensisynnyttäjillä. Välilihan leikkaus-, repeämä- tai keisarileikkaushaavat olivat täysin parantuneet suurimmalla osalla naisista kolmen kuukauden kuluttua synnytyksestä. Yleisimpiä naisten kokemia oireita ensimmäisen vuoden aikana synnytyksestä olivat emättimen kostumisen vaikeus, yhdyntäkivut, peräpukamat sekä arpikudoksen kipu ja kiristys. Sukupuolinen halukkuus ja tyytyväisyys seksielämään olivat huonompaa ensimmäisen vuoden aikana synnytyksestä verrattuna aikaan ennen raskautta ja synnytystä. Synnytyksen aikaisella hoitotyöllä ja näyttöön perustuvalla synnytyksen ponnistusvaiheen hoidolla on suuri merkitys naisen synnytyskokemukseen, synnytyksen jälkeiseen vointiin ja seksuaaliterveyteen.