Analyzing changes in macro-level drivers of country-specific emissions : The role of consumption, technology and trade

Industrial ecology is an important field of sustainability science. It can be applied to study environmental problems in a policy relevant manner. Industrial ecology uses ecosystem analogy; it aims at closing the loop of materials and substances and at the same time reducing resource consumption and environmental emissions. Emissions from human activities are related to human interference in material cycles. Carbon (C), nitrogen (N) and phosphorus (P) are essential elements for all living organisms, but in excess have negative environmental impacts, such as climate change (CO2, CH4 N2O), acidification (NOx) and eutrophication (N, P). Several indirect macro-level drivers affect emissions change. Population and affluence (GDP/capita) often act as upward drivers for emissions. Technology, as emissions per service used, and consumption, as economic intensity of use, may act as drivers resulting in a reduction in emissions. In addition, the development of country-specific emissions is affected by international trade. The aim of this study was to analyse changes in emissions as affected by macro-level drivers in different European case studies. ImPACT decomposition analysis (IPAT identity) was applied as a method in papers I III. The macro-level perspective was applied to evaluate CO2 emission reduction targets (paper II) and the sharing of greenhouse gas emission reduction targets (paper IV) in the European Union (EU27) up to the year 2020. Data for the study were mainly gathered from official statistics. In all cases, the results were discussed from an environmental policy perspective. The development of nitrogen oxide (NOx) emissions was analysed in the Finnish energy sector during a long time period, 1950 2003 (paper I). Finnish emissions of NOx began to decrease in the 1980s as the progress in technology in terms of NOx/energy curbed the impact of the growth in affluence and population. Carbon dioxide (CO2) emissions related to energy use during 1993 2004 (paper II) were analysed by country and region within the European Union. Considering energy-based CO2 emissions in the European Union, dematerialization and decarbonisation did occur, but not sufficiently to offset population growth and the rapidly increasing affluence during 1993 2004. The development of nitrogen and phosphorus load from aquaculture in relation to salmonid consumption in Finland during 1980 2007 was examined, including international trade in the analysis (paper III). A regional environmental issue, eutrophication of the Baltic Sea, and a marginal, yet locally important source of nutrients was used as a case. Nutrient emissions from Finnish aquaculture decreased from the 1990s onwards: although population, affluence and salmonid consumption steadily increased, aquaculture technology improved and the relative share of imported salmonids increased. According to the sustainability challenge in industrial ecology, the environmental impact of the growing population size and affluence should be compensated by improvements in technology (emissions/service used) and with dematerialisation. In the studied cases, the emission intensity of energy production could be lowered for NOx by cleaning the exhaust gases. Reorganization of the structure of energy production as well as technological innovations will be essential in lowering the emissions of both CO2 and NOx. Regarding the intensity of energy use, making the combustion of fuels more efficient and reducing energy use are essential. In reducing nutrient emissions from Finnish aquaculture to the Baltic Sea (paper III) through technology, limits of biological and physical properties of cultured fish, among others, will eventually be faced. Regarding consumption, salmonids are preferred to many other protein sources. Regarding trade, increasing the proportion of imports will outsource the impacts. Besides improving technology and dematerialization, other viewpoints may also be needed. Reducing the total amount of nutrients cycling in energy systems and eventually contributing to NOx emissions needs to be emphasized. Considering aquaculture emissions, nutrient cycles can be partly closed through using local fish as feed replacing imported feed. In particular, the reduction of CO2 emissions in the future is a very challenging task when considering the necessary rates of dematerialisation and decarbonisation (paper II). Climate change mitigation may have to focus on other greenhouse gases than CO2 and on the potential role of biomass as a carbon sink, among others. The global population is growing and scaling up the environmental impact. Population issues and growing affluence must be considered when discussing emission reductions. Climate policy has only very recently had an influence on emissions, and strong actions are now called for climate change mitigation. Environmental policies in general must cover all the regions related to production and impacts in order to avoid outsourcing of emissions and leakage effects. The macro-level drivers affecting changes in emissions can be identified with the ImPACT framework. Statistics for generally known macro-indicators are currently relatively well available for different countries, and the method is transparent. In the papers included in this study, a similar method was successfully applied in different types of case studies. Using transparent macro-level figures and a simple top-down approach are also appropriate in evaluating and setting international emission reduction targets, as demonstrated in papers II and IV. The projected rates of population and affluence growth are especially worth consideration in setting targets. However, sensitivities in calculations must be carefully acknowledged. In the basic form of the ImPACT model, the economic intensity of consumption and emission intensity of use are included. In seeking to examine consumption but also international trade in more detail, imports were included in paper III. This example demonstrates well how outsourcing of production influences domestic emissions. Country-specific production-based emissions have often been used in similar decomposition analyses. Nevertheless, trade-related issues must not be ignored.

Substrate Selectivity and Molecular Adaptation in the Outer Membrane Proteases of Yersinia pestis and Salmonella enterica

Proteolysis is important in bacterial pathogenesis and colonization of animal and plant hosts. In this work I have investigated the functions of the bacterial outer membrane proteases, omptins, of Yersinia pestis and Salmonella enterica. Y. pestis is a zoonotic pathogen that causes plague and has evolved from gastroenteritis-causing Yersinia pseudotuberculosis about 13 000 years ago. S. enterica causes gastroenteritis and typhoid fever in humans. Omptins are transmembrane β-barrels with ten antiparallel β-strands and five surface-exposed loops. The loops are important in substrate recognition, and variation in the loop sequences leads to different substrate selectivities between omptins, which makes omptins an ideal platform to investigate functional adaptation and to alter their polypeptide substrate preferences. The omptins Pla of Y. pestis and PgtE of S. enterica are 75% identical in their amino acid sequences. Pla is a multifunctional protein with proteolytic and non-proteolytic functions, and it increases bacterial penetration and proliferation in the host. Functions of PgtE increase migration of S. enterica in vivo and bacterial survival in mouse macrophages, thus enhancing bacterial spread within the host. Mammalian plasminogen/fibrinolytic system maintains the balance between coagulation and fibrinolysis and participates in several cellular processes, e.g., cell migration and degradation of extracellular matrix proteins. This system consists of activation cascades, which are strictly controlled by several regulators, such as plasminogen activator inhibitor 1 (PAI-1), α2-antiplasmin (α2AP), and thrombin-activatable fibrinolysis inhibitor (TAFI). This work reveals novel interactions of the omptins of Y. pestis and S. enterica with the regulators of the plasminogen/fibrinolytic system: Pla and PgtE inactivate PAI-1 by cleavage at the reactive site peptide bond, and degrade TAFI, preventing its activation to TAFIa. Structure-function relationship studies with Pla showed that threonine 259 of Pla is crucial in plasminogen activation, as it prevents degradation of the plasmin catalytic domain by the omptin and thus maintains plasmin stability. In this work I constructed chimeric proteins between Pla and Epo of Erwinia pyrifoliae that share 78% sequence identity to find out which amino acids and regions in Pla are important for its functions. Epo is neither a plasminogen activator nor an invasin, but it degrades α2AP and PAI-1. Cumulative substitutions towards Pla sequence turned Epo into a Pla-like protein. In addition to threonine 259, loops 3 and 5 are critical in plasminogen activation by Pla. Turning Epo into an invasin required substitution of 31 residues located at the extracellular side of the Epo protein above the lipid bilayer, and also of the β1-strand in the N-terminal transmembrane region of the protein. These studies give an example of how omptins adapt to novel functions that advantage their host bacteria in different ecological niches.

Microbial life and deposits in paper machine circuits

Väitöskirjani käsittele mikrobien ja erilaisten kemikaalien rooleja saostumien ja biofilmien muodostumisessa paperi- ja kartonkikoneilla. "Saostuma" tässä työssä tarkoittaa kiinteän aineen kertymää konepinnoille tai rajapinnoille konekierroissa, jotka on tarkoitettu massasulppujen, lietteiden, vesien tai ilman kuljetukseen. Saostumasta tulee "biofilmi" silloin kun sen oleellinen rakennekomponentti on mikrobisolut tai niiden tuotteet. Väitöstyöni työhypoteesina oli, että i. tietämys saostumien koostumuksesta, sekä ii. niiden rakenteesta, biologisista, fysikaalis-kemiallisista ja teknisistä ominaisuuksista ohjaavat tutkijaa löytämään ympäristöä säästäviä keinoja estää epätoivottujen saostumien muodostus tai purkaa jo muodostuneita saostumia. Selvittääkseni saostumien koostumista ja rakennetta käytin monia erilaisia analytiikan työkaluja, kuten elektronimikroskopiaa, konfokaali-laser mikroskopiaa (CLSM), energiadispersiivistä röntgenanalyysiä (EDX), pyrolyysi kaasukromatografiaa yhdistettynä massaspektrometriaan (Py-GCMS), joninvaihtokromatografiaa, kaasukromatografiaa ja mikrobiologisia analyysejä. Osallistuin aktiivisesti innovatiivisen, valon takaisinsirontaan perustuvan sensorin kehittämistyöhön, käytettäväksi biofilmin kasvun mittaukseen suoraan koneen vesikierroista ja säiliöistä. Työni osoitti, että monet paperinvalmistuksessa käytetyistä kemikaaleista reagoivat keskenään tuottaen orgaanisia tahmakerroksia konekiertojen teräspinnoille. Löysin myös kerrostumia, jotka valomikroskooppisessa tarkastelussa oli tulkittu mikrobeiksi, mutta jotka elektronimikroskopia paljasti alunasta syntyneiksi, alumiinihydroksidiksi joka saostui pH:ssa 6,8 kiertokuitua käyttävän koneen viiravesistä. Monet paperintekijät käyttävät vieläkin alunaa kiinnitysaineena vaikka prosessiolot ovat muuttuneet happamista neutraaleiksi. Sitä pidetään paperitekijän "aspiriinina", mutta väitöstutkimukseni osoitti sen riskit. Löysin myös orgaanisia saostumia, joiden alkuperä oli aineiden, kuten pihkan, saippuoituminen (kalsium saippuat) niin että muodostui tahmankasvua ylläpitävä alusta monilla paperi- ja kartonkikoneilla. Näin solumuodoiltaan Deinococcus geothermalista muistuttavia bakteereita kasvamassa lujasti teräskoepalojen pintaan kiinnittyneinä pesäkkeinä, kun koepaloja upotettiin paperikoneiden vesikiertoihin. Nämä deinokokkimaiset pesäkkeet voivat toimia jalustana, tarttumisalustana muiden mikrobien massoille, joka selittäisi miksi saostumat yleisesti sisältävät deinokokkeja pienenä, muttei koskaan pääasiallisena rakenneosana. Kun paperikoneiden käyttämien vesien (raakavedet, lämminvesi, biologisesti puhdistettu jätevesi) laatua tutkitaan, mittausmenetelmällä on suuri merkitys. Koepalan upotusmenetelmällä todettu biofilmikasvu ja viljelmenetelmällä mitattu bakteerisaastuneisuus korreloivat toisiinsa huonosti etenkin silloin kun likaantumisessa oli mukana rihmamaiseti kasvavia bakteereja. Huoli ympäristöstä on pakottanut paperi- ja kartonkikoneiden vesikiertojen sulkemiseen. Vesien kierrätys ja prosessivesien uudelleenkäyttö nostavat prosessilämpötilaa ja lisäävät koneella kiertävien kolloidisten ja liuenneiden aineiden määriä. Tutkin kiertovesien pitoisuuksia kolmessa eriasteisesti suljetussa tehtaassa, joiden päästöt olivat 0 m3, 0,5 m3 ja 4 m3 jätevettä tuotetonnia kohden, perustuen puhdistetun jäteveden uudelleen käyttöön. Nollapäästöisellä tehtaalla kiertovesiin kertyi paljon orgaanisesti sidottua hiiltä (> 10 g L-1), etenkin haihtuvina happoina (maito-, etikka-, propioni- ja voi-). Myös sulfaatteja, klorideja, natriumia ja kalsiumia kertyi paljon, > 1 g L-1 kutakin. Pääosa (>40%) kaikista bakteereista oli 16S rRNA geenisekvenssianalyysien tulosten perusteella sukua, joskin etäistä (< 96%) ainoastaan Enterococcus cecorum bakteerille. 4 m3 päästävältä tehtaalta löytyi lisäksi Bacillus thermoamylovorans ja Bacillus coagulans. Tehtaiden saostumat sisälsivät arkkeja suurina pitoisuuksina, ≥ 108 g-1, mutta tunnistukseen riittävää sekvenssisamanlaisuutta löytyi vain yhteen arkkisukuun, Methanothrix. Tutkimustulokset osoittivat että tehtaan vesikiertojen sulkeminen vähensi rajusti mikrobiston monimuotoisuutta, muttei estänyt liuenneen aineen ja kiintoaineen mineralisoitumista.

Keittiömaailman matkassa 20 vuotta : Tutkimus erään keittiökalustevalmistajan johtavan markkina-aseman rakentamisesta ja säilyttämisestä

A View into the World of Kitchen: Development and retention of a leading position in the market of kitchen interiors - a case study of 20 years. This study focuses on the development of a kitchen interiors company, presently called Novart Inc., into the leading company of the industry from 1980´s to the present. The objective of the study is to describe the effects of strategic choices, the decisions of the management and the owner´s direction and control to the build up and the retaining of the leading position in the market. From theory point of view, strategic choices refer to com-pany purchases as corporate-level strategies, and business and marketing strategies. The empirical research was carried out in two phases and it is based on various company documents and records, and on the intensive interviews of seven key executives in the company. An abductive research design was utilized. The company gained the leading position in the kitchen market in Finland by company purchases, and the company has been able to retain the position. Firstly the goal was to expand to retail market and, secondly, the company has maintained the balance of supply and demand by closing the purchased production units when needed. The simultaneous use of these two strategic goals is a kind of a new observation, and the strategy may be suitable only for market leaders. During the latter part of the research period the strategy of com-pany purchases has been abandoned and the leading position in the market has been main-tained by developing systematically business and marketing capability. In the business and marketing strategies the distribution channels and the brands have been emphasized. During the research period the company has almost totally abandoned the long distribution channels and started to use its own channels built and named after the main brands. These are A la Carte, Parma and Petra. At the moment, in the beginning of the 21st century, a new distribution channel, the concept of the Kitchen World, is being built in addition to the channels mentioned above. The management´s decision making and the implementation the decisions have been well-considered. The executives emphasized the valuing of the importance of the decisions dif-ferently except the two decisions named the most important ones, i.e., the decisions to start own production of the raw material and to concentrate the business only to one company. The executive staff has also succeeded in managing crisis and threats of bankruptcy, and the company has been managed profitable. During all the four terms of ownership: Puolimatka Corporation, the Hankkija/Novera Corporation, the ownership period of the "bank", and the Nobia Corporate the ownership direction and control has been somewhat different. All the owners have paid attention to economic issues. The direction of cash flows and investments was at its strongest during the Hankkija/Novera term. For the last owner Nobia the production and marketing of the kitchen interiors has been the core business, which thus has strengthened the business and marketing capabilities of the target company of this research. A common denominator during all the four terms of ownership has been owners' trust gained by the professional skills of the management of the target company. This has lead to greater independence of the management of the company and less owners´ direction. Keywords: leading position, marketing strategy, management decisions, acquisition, corporate governance

On the Geometry of Infinite-Dimensional Grassmannian Manifolds and Gauge Theory

This PhD Thesis is about certain infinite-dimensional Grassmannian manifolds that arise naturally in geometry, representation theory and mathematical physics. From the physics point of view one encounters these infinite-dimensional manifolds when trying to understand the second quantization of fermions. The many particle Hilbert space of the second quantized fermions is called the fermionic Fock space. A typical element of the fermionic Fock space can be thought to be a linear combination of the configurations m particles and n anti-particles . Geometrically the fermionic Fock space can be constructed as holomorphic sections of a certain (dual)determinant line bundle lying over the so called restricted Grassmannian manifold, which is a typical example of an infinite-dimensional Grassmannian manifold one encounters in QFT. The construction should be compared with its well-known finite-dimensional analogue, where one realizes an exterior power of a finite-dimensional vector space as the space of holomorphic sections of a determinant line bundle lying over a finite-dimensional Grassmannian manifold. The connection with infinite-dimensional representation theory stems from the fact that the restricted Grassmannian manifold is an infinite-dimensional homogeneous (Kähler) manifold, i.e. it is of the form G/H where G is a certain infinite-dimensional Lie group and H its subgroup. A central extension of G acts on the total space of the dual determinant line bundle and also on the space its holomorphic sections; thus G admits a (projective) representation on the fermionic Fock space. This construction also induces the so called basic representation for loop groups (of compact groups), which in turn are vitally important in string theory / conformal field theory. The Thesis consists of three chapters: the first chapter is an introduction to the backround material and the other two chapters are individually written research articles. The first article deals in a new way with the well-known question in Yang-Mills theory, when can one lift the action of the gauge transformation group on the space of connection one forms to the total space of the Fock bundle in a compatible way with the second quantized Dirac operator. In general there is an obstruction to this (called the Mickelsson-Faddeev anomaly) and various geometric interpretations for this anomaly, using such things as group extensions and bundle gerbes, have been given earlier. In this work we give a new geometric interpretation for the Faddeev-Mickelsson anomaly in terms of differentiable gerbes (certain sheaves of categories) and central extensions of Lie groupoids. The second research article deals with the question how to define a Dirac-like operator on the restricted Grassmannian manifold, which is an infinite-dimensional space and hence not in the landscape of standard Dirac operator theory. The construction relies heavily on infinite-dimensional representation theory and one of the most technically demanding challenges is to be able to introduce proper normal orderings for certain infinite sums of operators in such a way that all divergences will disappear and the infinite sum will make sense as a well-defined operator acting on a suitable Hilbert space of spinors. This research article was motivated by a more extensive ongoing project to construct twisted K-theory classes in Yang-Mills theory via a Dirac-like operator on the restricted Grassmannian manifold.

The Pseudomonas syringae-derived HrpA pilins - molecular characterization and biotechnological application of the transcripts

Many Gram-negative bacteria pathogenic to plants and animals possess type III secretion systems that are used to cause disease. Effector proteins are injected into host cells using the type III secretion machineries. Despite vigorous studies, the nature of the secretion signal for type III secreted proteins still remains elusive. Both mRNA and proteinaceous signals have been proposed. Findings on coupling of translation to secretion by the type III secretion systems are also still contradictory. This study dealt with the secretion signal of HrpA from Pseudomonas syringae pathovar tomato. HrpA is the major component of the type III secretion system-associated Hrp pilus and a substrate for the type III secretion systems. The secretion signal was shown to reside in the first 15 codons or amino acids, a location typical for type III secretion signals. Translation of HrpA in the absence of a functional type III secretion system was established, but it does not exclude the possibility of coupling of translation to secretion when the secretion apparatus is present. The hrpA transcripts from various unrelated plant pathogenic bacteria were shown to be extremely stable. The biological relevance of this observation is unknown, but possible explanations include the high prevalence of HrpA protein, an mRNA secretion signal or timing of secretion. The hrpA mRNAs are stable over a wide range of temperatures, in the absence of translating ribosomes and even in the heterologous host Escherichia coli. The untranslated regions (UTRs) of hrpA transcripts from at least 20 pathovars of Pseudomonas syringae are highly homologous, whilst their coding regions exhibit low similarity. The stable nature of hrpA messenger RNAs is likely to be due to the folding of their 5 and 3 UTRs. In silico the UTRs seem to form stem-loop structures, the hairpin structures in the 3 UTRs being rich in guanidine and cytosine residues. The stable nature of the hrpA transcript redirected the studies to the stabilization of heterologous transcripts and to the use of stable messenger RNAs in recombinant protein production. Fragments of the hrpA transcript can be used to confer stability on heterologous transcripts from several sources of bacterial and eukaryotic origin, and to elevate the levels of production of the corresponding recombinant proteins several folds. hrpA transcript stabilizing elements can be used for improving the yields of recombinant proteins even in Escherichia coli, one of the most commonly used industrial protein production hosts.

Harmful algae in the planktonic food web of the Baltic Sea

This study deals with algal species occurring commonly in the Baltic Sea: haptophyte Prymnesium parvum, dinoflagellates Dinophysis acuminata, D. norvegica and D. rotundata, and cyanobacterium Nodularia spumigena. The hypotheses are connected to the toxicity of the species, to the factors determining toxicity, to the consequences of toxicity and to the transfer of toxins in the aquatic food web. Since the Baltic Sea is severely eutrophicated, the fast-growing haptophytes have potential in causing toxic blooms. In our studies, the toxicity (as haemolytic activity) of the haptophyte P. parvum was highest under phosphorus-limited conditions, but the cells were toxic also under nitrogen limitation and under nutrient-balanced growth conditions. The cellular nutrient ratios were tightly related to the toxicity. The stoichiometric flexibility for cellular phosphorus quota was higher than for nitrogen, and nitrogen limitation led to decreased biomass. Negative allelopathic effects on another algae (Rhodomonas salina) could be observed already at low P. parvum cell densities, whereas immediate lysis of R. salina cells occurred at P. parvum cell densities corresponding to natural blooms. Release of dissolved organic carbon from the R. salina cells was measured within 30 minutes, and an increase in bacterial number and biomass was measured within 23 h. Because of the allelopathic effect, formation of a P. parvum bloom may accelerate after a critical cell density is reached and the competing species are eliminated. A P. parvum bloom indirectly stimulates bacterial growth, and alters the functioning of the planktonic food web by increasing the carbon transfer through the microbial loop. Our results were the first reports on DSP toxins in Dinophysis cells in the Gulf of Finland and on PTX-2 in the Baltic Sea. Cellular toxin contents in Dinophysis spp. ranged from 0.2 to 149 pg DTX-1 cell-1 and from 1.6 to 19.9 pg PTX-2 cell-1 in the Gulf of Finland. D. norvegica was found mainly around the thermocline (max. 200 cells L-1), whereas D. acuminata was found in the whole mixed layer (max. 7 280 cells L-1). Toxins in the sediment trap corresponded to 1 % of DTX-1 and 0.01 % PTX-2 of the DSP pool in the suspended matter. This indicates that the majority of the DSP toxins does not enter the benthic community, but is either decomposed in the water column, or transferred to higher trophic levels in the planktonic food chain. We found that nodularin, produced by Nodularia spumigena, was transferred to the copepod Eurytemora affinis through three pathways: by grazing on filaments of small Nodularia, directly from the dissolved pool, and through the microbial food web by copepods grazing on ciliates, dinoflagellates and heterotrophic nanoflagellates. The estimated proportion of the microbial food web in nodularin transfer was 22-45 % and 71-76 % in our two experiments, respectively. This highlights the potential role of the microbial food web in the transfer of toxins in the planktonic food web.

Fine-tuning of the signalling network controlling morphogenesis and stem cell development in teeth

Tooth development is regulated by sequential and reciprocal interactions between epithelium and mesenchyme. The molecular mechanisms underlying this regulation are conserved and most of the participating molecules belong to several signalling families. Research focusing on mouse teeth has uncovered many aspects of tooth development, including molecular and evolutionary specifi cs, and in addition offered a valuable system to analyse the regulation of epithelial stem cells. In mice the spatial and temporal regulation of cell differentiation and the mechanisms of patterning during development can be analysed both in vivo and in vitro. Follistatin (Fst), a negative regulator of TGFβ superfamily signalling, is an important inhibitor during embryonic development. We showed the necessity of modulation of TGFβ signalling by Fst in three different regulatory steps during tooth development. First we showed that tinkering with the level of TGFβ signalling by Fst may cause variation in the molar cusp patterning and crown morphogenesis. Second, our results indicated that in the continuously growing mouse incisors asymmetric expression of Fst is responsible for the labial-lingual patterning of ameloblast differentiation and enamel formation. Two TGFβ superfamily signals, BMP and Activin, are required for proper ameloblast differentiation and Fst modulates their effects. Third, we identifi ed a complex signalling network regulating the maintenance and proliferation of epithelial stem cells in the incisor, and showed that Fst is an essential modulator of this regulation. FGF3 in cooperation with FGF10 stimulates proliferation of epithelial stem cells and transit amplifying cells in the labial cervical loop. BMP4 represses Fgf3 expression whereas Activin inhibits the repressive effect of BMP4 on the labial side. Thus, Fst inhibits Activin rather than BMP4 in the cervical loop area and limits the proliferation of lingual epithelium, thereby causing the asymmetric maintenance and proliferation of epithelial stem cells. In addition, we detected Lgr5, a Wnt target gene and an epithelial stem cell marker in the intestine, in the putative epithelial stem cells of the incisor, suggesting that Lgr5 is a marker of incisor stem cells but is not regulated by Wnt/β-catenin signalling in the incisor. Thus the epithelial stem cells in the incisor may not be directly regulated by Wnt/β-catenin signalling. In conclusion, we showed in the mouse incisors that modulating the balance between inductive and inhibitory signals constitutes a key mechanism regulating the epithelial stem cells and ameloblast differentiation. Furthermore, we found additional support for the location of the putative epithelial stem cells and for the stemness of these cells. In the mouse molar we showed the necessity of fi ne-tuning the signalling in the regulation of the crown morphogenesis, and that altering the levels of an inhibitor can cause variation in the crown patterning.

Preterm Birth and Surgical Treatment of the Uterine Cervix

Cervical cancer is the second most common cancer among women globally. Most, probably all cases, arise through a precursor, cervical intraepithelial neoplasia (CIN). Effective cytological screening programmes and surgical treatments of precancerous lesions have dramatically reduced its prevalence and related mortality. Although these treatments are effective, they may have adverse effects on future fertility and pregnancy outcomes. The aim of this study was to evaluate the effects of surgical treatment of the uterine cervix on pregnancy and fertility outcomes, with the focus particularly on preterm birth. The general preterm birth rates and risk factors during 1987–2005 were studied. Long-term mortality rates of the treated women were studied. In this study, information from The Medical Birth Register (MBR), The Hospital Discharge Register (HDR), The Cause-of-Death Register (CDR), and hospital records were used. Treatments were performed during 1987–2003 and subsequent deliveries, IVF treatments and deaths were analyzed. The general preterm birth rate in Finland was relatively stable, varying from 5.1% to 5.4% during the study period (1987 to 2005), although the proportion of extremely preterm births had decreased substantially by 12%.The main risk factor as regards preterm birth was multiplicity, followed by elective delivery (induction of delivery or elective cesarean section), primiparity, in vitro fertilization treatment, maternal smoking and advanced maternal age. The risk of preterm birth and low birth weight was increased after any cervical surgical treatment; after conization the risk of preterm birth was almost two-fold (RR 1.99, 95% CI 1.81– 2.20). In the conization group the risk was the highest for very preterm birth (28–31 gestational weeks) and it was also high for extremely preterm birth (less than 28 weeks). In this group the perinatal mortality was also increased. In subgroup analysis, laser ablation was not associated with preterm birth. When comparing deliveries before and after Loop conization, we found that the risk of preterm birth was increased 1.94-fold (95% CI 1.10–3.40). Adjusting for age, parity, or both did not affect our results. Large or repeat cones increased the risk of preterm birth when compared with smaller cones, suggesting that the size of the removed cone plays a role. This was corroborated by the finding that repeat treatment increased the risk as much as five-fold when compared with the background preterm birth rate. We found that the proportion of IVF deliveries (1.6% vs. 1.5%) was not increased after treatment for CIN when adjusted for year of delivery, maternal age, or parity. Those women who received both treatment for CIN and IVF treatment were older and more often primiparous, which explained the increased risk of preterm birth. We also found that mortality rates were 17% higher among women previously treated for CIN. This excess mortality was particularly seen as regards increased general disease mortality and alcohol poisoning (by 13%), suicide (by 67%) and injury death (by 31%). The risk of cervical cancer was high, as expected (SMR 7.69, 95% CI 4.23–11.15). Women treated for CIN and having a subsequent delivery had decreased general mortality rate (by -22%), and decreased disease mortality (by -37%). However, those with preterm birth had increased general mortality (SMR 2.51, 95% CI 1.24–3.78), as a result of cardiovascular diseases, alcohol-related causes, and injuries. In conclusion, the general preterm birth rate has not increased in Finland, as in many other developed countries. The rate of extremely preterm births has even decreased. While other risk factors of preterm birth, such as multiplicity and smoking during pregnancy have decreased, surgical treatments of the uterine cervix have become more important risk factors as regards preterm birth. Cervical conization is a predisposing factor as regards preterm birth, low birth weight and even perinatal mortality. The most frequently used treatment modality, Loop conization, is also associated with the increased risk of preterm birth. Treatments should be tailored individually; low-grade lesions should not be treated at all among young women. The first treatment should be curative, because repeat treatments are especially harmful. The proportion of IVF deliveries was not increased after treatment for CIN, suggesting that current treatment modalities do not strongly impair fertility. The long-term risk of cervical cancer remains high even after many years post-treatment; therefore careful surveillance is necessary. In addition, accidental deaths and deaths from injury were common among treated women, suggesting risk-taking behavior of these women. Preterm birth seems be associated with extremely high mortality rates, due to cardiovascular, alcohol-related and injury deaths. These women could benefit from health counseling, for example encouragement in quitting smoking.