Merkel cell carcinoma : Epidemiological study with special reference to polyomavirus and vascular factors in pathogenesis

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy that occurs predominantly on sun exposed skin areas. A new polyomavirus (MCPyV) was identified in MCC tumor tissues in 2008 suggesting that a viral infection might be an etiological factor. A typical MCC is a rapidly growing painless purple nodule. In its early stage it can be misjudged by its appearance as a cyst or abscess. Recurrences are common and approximately half of the patients will develop lymph node metastases and third of the patents will have distant metastases. It affects mostly elderly persons at an average age of 70 at the time of diagnosis. MCC was first described in 1972 and the first MCC patient in Finland was identified in 1983. MCC has been poorly recognized, but increased awareness and better diagnostic accuracy has increased the incidence since the early years. In this study, all cases with a notation of MCC during 1979 2008 were obtained from the Finnish Cancer Registry. Based on this data, the incidence is 0.11 for men and 0.12 for women. It is similar than that of other Nordic countries, but lower than in the USA. For clinical series, the files of patients diagnosed with MCC during 1983 2004 were reviewed, and the tissue samples were re-evaluated, if available (n=181). Third of the patients were men, and the most common site of the primary tumor was the head and neck (53%). The majority of the patients (86%) presented with a clinically node-negative (Stage I or II) disease, but the disease recurred in 38% of them. The treatment schemes were heterogeneous. No additional benefit from a wide margin (≥2 cm) was found compared to a margin of 0.1-1.9 cm, but intralesional excision was more often associated with local recurrence. None of the patients with Stage I-II disease who had received postoperative radiotherapy had local recurrence during the follow-up period. The 5-year relative survival ratio for Stage I disease was 68%, for Stage II 67%, for Stage III 16%, and for Stage IV 0%. The relative excess risk of death was significantly lower among women than among men. Some of these tissue samples were further analyzed for vascular invasion (n=126) by immunohistochemistry using vascular endothelial markers CD-31 and D2-40. Vascular invasion was seen in 93% of the samples and it was observed already in very small, <5mm tumors. The tissue samples were also analyzed for the presence of MCPyV by using a polymerase chain reaction (PCR) and quantitative PCR. MCPyV DNA was present in 80% of 114 samples studied. The patients with virus-positive tumors had better overall survival than patients with virus-negative tumors. Immunohistochemical analyses were performed for the expression of VEGFR-2 (n=21) and endostatin (n=19), but they had no prognostic value. Our results support the concept of treating MCC with margin-negative excision and radiotherapy to the tumor bed to reduce local recurrence. The finding of a high frequency of lymphovascular invasion reduces its value as a prognostic factor, but emphasizes the role of sentinel node biopsy even in very small primary MCC.

Novel Approaches to the Sampling of Atmospheric Aerosols and Determination of Chemical Composition

The Earth s climate is a highly dynamic and complex system in which atmospheric aerosols have been increasingly recognized to play a key role. Aerosol particles affect the climate through a multitude of processes, directly by absorbing and reflecting radiation and indirectly by changing the properties of clouds. Because of the complexity, quantification of the effects of aerosols continues to be a highly uncertain science. Better understanding of the effects of aerosols requires more information on aerosol chemistry. Before the determination of aerosol chemical composition by the various available analytical techniques, aerosol particles must be reliably sampled and prepared. Indeed, sampling is one of the most challenging steps in aerosol studies, since all available sampling techniques harbor drawbacks. In this study, novel methodologies were developed for sampling and determination of the chemical composition of atmospheric aerosols. In the particle-into-liquid sampler (PILS), aerosol particles grow in saturated water vapor with further impaction and dissolution in liquid water. Once in water, the aerosol sample can then be transported and analyzed by various off-line or on-line techniques. In this study, PILS was modified and the sampling procedure was optimized to obtain less altered aerosol samples with good time resolution. A combination of denuders with different coatings was tested to adsorb gas phase compounds before PILS. Mixtures of water with alcohols were introduced to increase the solubility of aerosols. Minimum sampling time required was determined by collecting samples off-line every hour and proceeding with liquid-liquid extraction (LLE) and analysis by gas chromatography-mass spectrometry (GC-MS). The laboriousness of LLE followed by GC-MS analysis next prompted an evaluation of solid-phase extraction (SPE) for the extraction of aldehydes and acids in aerosol samples. These two compound groups are thought to be key for aerosol growth. Octadecylsilica, hydrophilic-lipophilic balance (HLB), and mixed phase anion exchange (MAX) were tested as extraction materials. MAX proved to be efficient for acids, but no tested material offered sufficient adsorption for aldehydes. Thus, PILS samples were extracted only with MAX to guarantee good results for organic acids determined by liquid chromatography-mass spectrometry (HPLC-MS). On-line coupling of SPE with HPLC-MS is relatively easy, and here on-line coupling of PILS with HPLC-MS through the SPE trap produced some interesting data on relevant acids in atmospheric aerosol samples. A completely different approach to aerosol sampling, namely, differential mobility analyzer (DMA)-assisted filter sampling, was employed in this study to provide information about the size dependent chemical composition of aerosols and understanding of the processes driving aerosol growth from nano-size clusters to climatically relevant particles (>40 nm). The DMA was set to sample particles with diameters of 50, 40, and 30 nm and aerosols were collected on teflon or quartz fiber filters. To clarify the gas-phase contribution, zero gas-phase samples were collected by switching off the DMA every other 15 minutes. Gas-phase compounds were adsorbed equally well on both types of filter, and were found to contribute significantly to the total compound mass. Gas-phase adsorption is especially significant during the collection of nanometer-size aerosols and needs always to be taken into account. Other aims of this study were to determine the oxidation products of β-caryophyllene (the major sesquiterpene in boreal forest) in aerosol particles. Since reference compounds are needed for verification of the accuracy of analytical measurements, three oxidation products of β-caryophyllene were synthesized: β-caryophyllene aldehyde, β-nocaryophyllene aldehyde, and β-caryophyllinic acid. All three were identified for the first time in ambient aerosol samples, at relatively high concentrations, and their contribution to the aerosol mass (and probably growth) was concluded to be significant. Methodological and instrumental developments presented in this work enable fuller understanding of the processes behind biogenic aerosol formation and provide new tools for more precise determination of biosphere-atmosphere interactions.

Hila- ja kuviotason laskennan vaikutus kuvion kokonaistilavuuteen, tallennustilaan ja laskentaaikaan teoreettista läpimittajakaumaa ja runkolukusarjaa käyttämällä

Metsäsuunnittelussa tarvittavan metsävaratiedon keräämisessä ollaan Suomessa siirtymässä kuvioittaisesta arvioinnista laserkeilaus- ja ilmakuvapohjaiseen kaukokartoitukseen. Tämän tutkimuksen tarkoitus oli selvittää kuvion kokonaistilavuuden ja läpimittajakauman ennustamisen tarkkuus koealan metsikkö- ja puustotunnuksista MSN-, PRM-, ML- ja FMM-menetelmiä sekä Weibull-jakaumaa hyödyntäen seuraavilla tavoilla: 1. PRM-menetelmällä hilatasolla, 2. PRMmenetelmällä kuviotasolla, 3. ML-menetelmällä hilatasolla ja 4. ML-menetelmällä kuviotasolla. Lisäksi kuvion kokonaistilavuuden ennustamisen tarkkuus selvitettiin hyödyntäen kuviolle tuotettua runkolukusarjaa. Tulokset laskettiin puulajikohtaisesti männylle, kuuselle, koivulle ja muille puulajeille. Puulajien tulokset laskettiin kuviotasolla yhteen. Lisäksi selvitettiin menetelmien laskenta-ajan ja tallennustilan tarve. Tutkimuksen aineistona käytettiin Hämeen ammattikorkeakoulun Evon toimipisteen metsistä mitattuja kiinteäsäteisiä ympyräkoealoja, joita oli 249 kappaletta. Hakkuukoneella mitattiin 12kuvion, joiden pinta-alat vaihtelivat välillä 0,2 – 1,94 hehtaaria, puustotiedot. Aluepohjaisen laserkeilausaineiston pulssin tiheys oli 1,8/m2 ja ilmakuvien pikselikoko 0,5 metriä. Kuvion kokonaistilavuus ennustettiin tai estimoitiin laserkeilaus- ja ilmakuva-aineiston piirteiden avulla koealojen puustotunnuksista. Tulokset laskettiin erikseen kaikille kuvioille ja kuvioille, joiden pinta-ala oli yli 0,5 hehtaaria. Yli 0,5 hehtaarin kuvioita oli 8 kappaletta. Kuvion hilojen naapureina käytettiin 1 - 10 koealaa. Menetelmästä ja naapurien määrästä riippuen kokonaistilavuuden suhteellinen RMSE ja harha vaihtelivat välillä 20,76 – 52,86 prosenttia ja -12,04 – 46,54 prosenttia. Vastaavat luvut yli 0,5 hehtaarin kuvioilla olivat 6,74 – 59,41 prosenttia ja -8,04 – 49,59 prosenttia. Laskenta-aika vaihteli menetelmien ja käytettyjen naapurien määrän mukaan voimakkaasti. Kehittyneemmällä ohjelmoinnilla ja ohjelmistolla laskenta-ajat voivat laskea merkittävästi. Tallennustila ei testatuilla menetelmillä ole rajoittava tekijä laajassakaan mittakaavassa. Läpimittajakauman perusteella PRM-menetelmä ennustaa puulajille erittäin kapean läpimittajakauman, jos koeala koostuu vain muutamasta lähes samankokoisesta puusta. Tämä vaikutti tuloksiin erityisesti menetelmällä PRM2.

Puunoston kehittäminen Stora Enso Metsän Helsingin palvelupisteessä

The operation environment in the roundwood trade in Finland in the 1990’s include several changes. They are changes in the structure of non-industrial private forest (NIPF) ownership, forest taxation, in forest legislation, in price recommendation agreement, diminishing resources of forestry extension services, etc. At the same time, the roundwood demand has been rising. All these developments cause uncertainty in wood procurement organisations, and call for research to find out how to adapt into the changing environment. The objective of this study is to produce information for roundwood purchasing planning and cus-tomer satisfaction management to be used by Stora Enso Metsä Customer Service, Helsinki. For this pur-pose, data needs to be gathered about the urban NIPFs and their forest estates, behaviour related to forestry and timber-selling, customer satisfaction in their latest timber selling transaction, and their opinions about Enso’s new customer service office and its service concept. To fulfil the objective of the study, a NIPF -owner -survey (N=1064, response rate 39,7%) was con-ducted in October 1998-January 1999. The sample was made on the basis of the marketing database of Stora Enso Oyj Forest Customer Service in Helsinki. In planning the frame of reference of the empirical study, the model of service quality by Grönroos was applied. The following aspects were included in the 7-page questionnaire: demographic, sosio-economic and forest estate background, relation to the forest service supply, behaviour related to forestry, timber-selling motives and behaviour, last contact organisation and its image in forestry business, expectations and percep-tions in the latest timber-selling transactions, and behavioural intentions. The results revealed that the share of women, pensioners and academically educated people among forest owners was quite high. The majority of the forest estates of the metropolitan forest owners were situ-ated in the provinces of South Finland and East Finland. The average forest estate area was considerably smaller than in a previous study. Economic and recreational objectives were most important in the use of forests. Forest Associations were involved in half of the roundwood sales transactions of the respondents in the metropolitan area. The wood quantity of transactions was considerably higher than the average in the whole country. Bank-organised forest-related activities, taxation infos and trips to the forest were the most popular activities. Among the services, silvicultural advices were needed mostly and stub treatment least. Brochure material related to stumpage timber sales and taxation were considered most important compared to material related to delivery sales. The service expectations were at highest for women and they were less satisfied with the service than men. 2nd and 3rd generation residents of the metropolitan area thought about the new customer service concept more positively than the 1st generation residents. Internet users under 60 years thought more positively about new satellite picture-based woodlot search concept. Cross-tabulation of factor scores against background variables indicated that women with relatively low education level a greater need to sell roundwood than entrepreneurs, white-collar workers and directors, and Internet users. Suspiciousness towards timber procurement organisations was relatively strong among women and those whose forest income share of the total income was either null or over 20 %. The average customer satisfaction score was negative in all nine questions. Statistical differences be-tween different companies did not exist in the average satisfaction scores. Stora Enso’s Helsinki forest cus-tomer service could choose the ability to purchase all timber grades as its competitive advantage. Out of nine service dimension included in the questionnaire, in this particular service dimension, Enso’s Helsinki forest customer service’s score exceeded most all organisations’ average customer satisfaction score. On the basis of importance – performance matrix, advice and quidance could have been provided more to the forest owners in their latest timber–selling transaction.

Legal Reasoning in Context

This study in EU law analyses the reasoning of the Court of Justice (the Court of Justice of the European Union) in a set of its preliminary rulings. Preliminary rulings are answers to national courts questions on the interpretation (and validity) of EU law called preliminary references. These questions concern specific legal issues that have arisen in legal disputes before the national courts. The Court of Justice alone has the ultimate authority to interpret EU law. The preliminary rulings bind the national courts in the cases giving rise to the preliminary reference, and the interpretations of EU law offered in the preliminary rulings are considered generally binding on all instances applying EU law. EU law is often described as a dynamic legal order and the Court of Justice as at the vanguard of developing it. It is generally assumed that the Court of Justice is striving to realise the EU s meta-level purpose (telos): integration. Against this backdrop one can understand the criticism the Court of Justice is often faced with in certain fields of EU law that can be described as developing. This criticism concerns the Court s (negatively) activist way of not just stating the law but developing or even making law. It is difficult to analyse or prove wrong this accusation as it is not in methodological terms clearly established what constitutes judicial activism, or more exactly where the threshold of negative activism lies. Moreover, one popular approach to assessing the role of the Court of Justice described as integration through law has become fairly political, neglecting to take into consideration the special nature of law as both facilitating and constraining action, not merely a medium for furthering integration. This study offers a legal reasoning approach of a more legalist nature, in order to balance the existing mix of approaches to explaining what the Court of Justice does and how. Reliance on legal reasoning is found to offer a working framework for analysis, whereas the tools for an analysis based on activism are found lacking. The legal reasoning approach enables one to assess whether or not the Court of Justice is pertaining to its own established criteria of interpretation of EU law, and if it is not, one should look more in detail at how the interpretation fits with earlier case-law and doctrines of EU law. This study examines the reasoning of the Court of Justice in a set of objectively chosen cases. The emphasis of the study is on analysing how the Court of Justice applies the established criteria of interpretation it has assumed for itself. Moreover, the judgments are assessed not only in terms of reasoning but also for meaningful silences they contain. The analysis is furthermore contextualised by taking into consideration how the cases were commented by legal scholars, their substantive EU law context, and also their larger politico-historical context. In this study, the analysis largely shows that the Court of Justice is interpreting EU law in accordance with its previous practice. Its reasoning retains connection with the linguistic or semiotic criteria of interpretation, while emphasis lies on systemic reasoning. Moreover, although there are a few judgments where the Court of Justice offers clearly dynamic reasoning or what can be considered as substantive reasoning stemming from, for example, common sense or reasonableness, such reasons are most often given in addition to systemic ones. In this sense and even when considered in its broader context, the case-law analysed in this study does not portray a specifically activist image of the Court of Justice. The legal reasoning approach is a valid alternative for explaining how and why the Court of Justice interprets EU law as it does.

Suokasvillisuuden vaste muuttuvaan ilmastoon: kokeellinen tutkimus kuivumisen vaikutuksesta

Soilla on merkittävä rooli ilmastonmuutoksen hillitsemisessä suuren hiilivarastonsa sekä ekosysteemin ja ilmakehän välisen kaasunvaihdon ansiosta. Ilmastonmuutoksen ennustetaan vaikuttavan suokasvillisuuteen ja suon toimintaan epäsuorasti. Vedenpinnan ennustetaan laskevan 14–21 cm johtuen kasveista ja avoimilta pinnoilta tapahtuvan haihdunnan lisääntymisestä lämpötilan noustessa, mikäli sadanta ei lisäänny. Aiemmat vedenpinnan laskun jälkeistä kasvillisuutta seuranneet tutkimukset ovat osoittaneet, että putkilokasvit hyötyvät alhaisemmasta vedenpinnan tasosta ja että kuljuun sopeutuneet rahkasammalet kärsivät kuivuneista oloista. Kasvillisuuden runsaussuhteiden muuttumisen lisäksi kasviyhteisöjen monimuotoisuus vähenee. Erityisen herkkiä vedenpinnan laskulle ovat olleet välipinta- ja kuljurahkasammalet ja sarat. Funktionaalisten kasviryhmien vasteiden selvittämiksesi käytettiin BACI (before-after-control-impact) –tutkimusotetta. Tutkimuksessa oli kolme verrokkialaa ja kolme käsittelyalaa, joissa vedenpintaa oli laskettu 14–21 senttimetriin. Lisäksi vertailukohdaksi tutkimuksessa oli mukana kolme alaa, joissa oli tehty metsäojitus n. 50 vuotta sitten. Nämä toistot sijaitsivat meso-, oligo ombrotrofisilla suotyypeillä Oriveden Lakkasuolla. Kasvillisuus kartoitettiin ja vedenpinnat mitattiin aloilta ennen käsittelyä vuonna 2000 sekä vuosina 2001–2003 ja 2009. Aineisto analysoitiin TWINSPAN- (PC-Ord), PRC ja DCA (CANOCO)-monimuuttujamenetelmillä. Tulokset osoittivat, että verrokki- ja käsittelyalat olivat samanlaisia lähtökohdiltaan, joten niitä voitiin käsittelyn jälkeen verrata toisiinsa. Kasvillisuuden rakenne vaihteli vuosien välillä myös verrokkialoilla, mikä osoittaa kasvien sopeutumiskyvyn muuttuviin sääoloihin (lämpötila, sademäärä). Vuosi 2003 erottui tutkimuksessa alhaisella vedenpinnantasolla, mutta toisaalta myös ainavihantien varpujen suuren peittävyyden osalta. Vuoteen 2009 mennessä kasvillisuuden erityisesti sarojen peittävyys väheni. Ravinteikkaimmilla toistoilla kasvillisuuden vasteet vaikuttivat olevan vahvemmat kuin vähäravinteisilla toistoilla. Kasviryhmistä kulju- ja välipintasammalilla oli vahvimmat vasteetvedenpinnan laskuun ja mätäslajeilla heikoimmat. Tulosten mukaan kasviryhmien vasteet vaihtelevat riippuen tarkasteltavasta aikajaksosta: ensimmäiset kolme vuotta käsittelyn jälkeen suo oli häiriötilassa ja vasta sen jälkeen kasvillisuus sopeutui muuttuneisiin oloihin.

Magnetically induced currents and magnetic response properties of molecules

The magnetically induced currents in organic monoring and multiring molecules, in Möbius shaped molecules and in inorganic all-metal molecules have been investigated by means of the Gauge-including magnetically induced currents (GIMIC) method. With the GIMIC method, the ring-current strengths and the ring-current density distributions can be calculated. For open-shell molecules, also the spin current can be obtained. The ring-current pathways and ring-current strengths can be used to understand the magnetic resonance properties of the molecules, to indirectly identify the effect of non-bonded interactions on NMR chemical shifts, to design new molecules with tailored properties and to discuss molecular aromaticity. In the thesis, the magnetic criterion for aromaticity has been adopted. According to this, a molecule which has a net diatropic ring current might be aromatic. Similarly, a molecule which has a net paratropic current might be antiaromatic. If the net current is zero, the molecule is nonaromatic. The electronic structure of the investigated molecules has been resolved by quantum chemical methods. The magnetically induced currents have been calculated with the GIMIC method at the density-functional theory (DFT) level, as well as at the self-consistent field Hartree-Fock (SCF-HF), at the Møller-Plesset perturbation theory of the second order (MP2) and at the coupled-cluster singles and doubles (CCSD) levels of theory. For closed-shell molecules, accurate ring-current strengths can be obtained with a reasonable computational cost at the DFT level and with rather small basis sets. For open-shell molecules, it is shown that correlated methods such as MP2 and CCSD might be needed to obtain reliable charge and spin currents. The basis set convergence has to be checked for open-shell molecules by performing calculations with large enough basis sets. The results discussed in the thesis have been published in eight papers. In addition, some previously unpublished results on the ring currents in the endohedral fullerene Sc3C2@C80 and in coronene are presented. It is shown that dynamical effects should be taken into account when modelling magnetic resonance parameters of endohedral metallofullerenes such as Sc3C2@C80. The ring-current strengths in a series of nano-sized hydrocarbon rings are related to static polarizabilities and to H-1 nuclear magnetic resonance (NMR) shieldings. In a case study on the possible aromaticity of a Möbius-shaped [16]annulene we found that, according to the magnetic criterion, the molecule is nonaromatic. The applicability of the GIMIC method to assign the aromatic character of molecules was confirmed in a study on the ring currents in simple monocylic aromatic, homoaromatic, antiaromatic, and nonaromatic hydrocarbons. Case studies on nanorings, hexaphyrins and [n]cycloparaphenylenes show that explicit calculations are needed to unravel the ring-current delocalization pathways in complex multiring molecules. The open-shell implementation of GIMIC was applied in studies on the charge currents and the spin currents in single-ring and bi-ring molecules with open shells. The aromaticity predictions that are made based on the GIMIC results are compared to other aromaticity criteria such as H-1 NMR shieldings and shifts, electric polarizabilities, bond-length alternation, as well as to predictions provided by the traditional Hückel (4n+2) rule and its more recent extensions that account for Möbius twisted molecules and for molecules with open shells.