Kuivumiskutistuman yhteys massaseosten ominaisuuksien synergiseen käyttäytymiseen

Diplomityön tavoitteena oli selvittää kuivumiskutistuman yhteyttä massojen synergiseen käyttäytymiseen. Kirjallisuusosassa on pohdittu kuitujen, kuitujen koostumuksen ja massaseosten ominaisuuksien vaikutusta kuivumiskutistumiseen. Lisäksi on pohdittu erilaisten kuivatustapojen vaikutusta kuivumiskutistuman suuruuteen ja SC-paperin mekaanisiin ominaisuuksiin. Kokeellisessa osassa valmistettiin kiertovedellä seosarkkeja. Massoina seoksissa käytettiin hioketta, TMP:tä ja kahta eri valmistajan sellua, jotka molemmat koostuivat kuusesta ja männystä. Seosarkkeja kuivattiin vapaasti, estetysti ja siten, että arkkia vedettiin konesuunnassa 2 % ja siten, että arkin annettiin kutistua konesuunnassa 2 %. Vapaasti kutistuneista arkeista mitattiin kuivumiskutistuma, käyttäen mahdollisimman tarkkaa menetelmää, jotta saatiin selville kunkin massaseoksen ja puhtaan massan kutistumapotentiaali. Kokeellisen osan mittaustulosten perusteella työssä pohdittiin kuivumiskutistumisen yhteyttä massojen synergiseen käyttäytymiseen. Tuloksista käy ilmi, että kuivumiskutistumalla on yhteys massaseosten synergiseen käyttäytymiseen. Kuivumiskutistuma vaikuttaa eniten selluilla, joilla on suurin kutistumispotentiaali. Arkin kuivuessa, kuitujen kutistuessa, rikkoutuu arkissa jo syntyneitä sidoksia heikentäen mm. vetolujuutta. Sidoksien rikkoutuminen ilmenee selvästi valonsironnan kasvamisena, mutta myös palstautumislujuuden huonontumisena, joka kertoo sidosten vähentymisestä. Selluosuuden kasvattaminen vaikuttaa useimpien arkin ominaisuuksia huonontaen ja siis synergiaa huonontaen. Puhtaita massoja vertaillessa puhtailla selluilla on useimpien ominaisuuksien kohdalla huonoimmat suhteellisesti saavutetut lujuudet, joten selluista ei saada kaikkea lujuuspotentiaalia, mikä taas näkyy selvästi selluosuuden kasvaessa suurempana poikkeamina additiivisesti lasketuista lujuuksista. Mekaanisilla massoilla, joilla on pienempi kuivumiskutistuma, ei vaikutus ole niin voimakas kuin selluilla ja puhtaat mekaaniset massat säilyttävätkin ominaisuutensa paremmin kuin sellut.

Implementation of bayesian therapeutic drug monitoring in modern patient care

The variability observed in drug exposure has a direct impact on the overall response to drug. The largest part of variability between dose and drug response resides in the pharmacokinetic phase, i.e. in the dose-concentration relationship. Among possibilities offered to clinicians, Therapeutic Drug Monitoring (TDM; Monitoring of drug concentration measurements) is one of the useful tool to guide pharmacotherapy. TDM aims at optimizing treatments by individualizing dosage regimens based on blood drug concentration measurement. Bayesian calculations, relying on population pharmacokinetic approach, currently represent the gold standard TDM strategy. However, it requires expertise and computational assistance, thus limiting its large implementation in routine patient care. The overall objective of this thesis was to implement robust tools to provide Bayesian TDM to clinician in modern routine patient care. To that endeavour, aims were (i) to elaborate an efficient and ergonomic computer tool for Bayesian TDM: EzeCHieL (ii) to provide algorithms for drug concentration Bayesian forecasting and software validation, relying on population pharmacokinetics (iii) to address some relevant issues encountered in clinical practice with a focus on neonates and drug adherence. First, the current stage of the existing software was reviewed and allows establishing specifications for the development of EzeCHieL. Then, in close collaboration with software engineers a fully integrated software, EzeCHieL, has been elaborated. EzeCHieL provides population-based predictions and Bayesian forecasting and an easy-to-use interface. It enables to assess the expectedness of an observed concentration in a patient compared to the whole population (via percentiles), to assess the suitability of the predicted concentration relative to the targeted concentration and to provide dosing adjustment. It allows thus a priori and a posteriori Bayesian drug dosing individualization. Implementation of Bayesian methods requires drug disposition characterisation and variability quantification trough population approach. Population pharmacokinetic analyses have been performed and Bayesian estimators have been provided for candidate drugs in population of interest: anti-infectious drugs administered to neonates (gentamicin and imipenem). Developed models were implemented in EzeCHieL and also served as validation tool in comparing EzeCHieL concentration predictions against predictions from the reference software (NONMEM®). Models used need to be adequate and reliable. For instance, extrapolation is not possible from adults or children to neonates. Therefore, this work proposes models for neonates based on the developmental pharmacokinetics concept. Patients' adherence is also an important concern for drug models development and for a successful outcome of the pharmacotherapy. A last study attempts to assess impact of routine patient adherence measurement on models definition and TDM interpretation. In conclusion, our results offer solutions to assist clinicians in interpreting blood drug concentrations and to improve the appropriateness of drug dosing in routine clinical practice.

Laminaatin toiminnallisten ominaisuuksien hallinta

Lattialaminaatti on kerrosrakenteinen levymateriaali. Tässä työssä tutkittiin laminaatin epäsymmetrisen kerrosrakenteen aiheuttamaa taipumusta käyristymiseen. Työn tavoitteena oli kehittää lattialaminaatin käyristymän hallintaan käytettävää taustapaperia niin, että käyristymää ei tapahtuisi tai käyristymä olisi lievästi alapintaa kohden heti puristuksen jälkeen ja säilyisi samanlaisena varastoinnissa. Kehityksessä huomioitiin taustan ulkonäkö. Taustapapereita valmistettiin sekä pilot- että tuotantomittakaavassa. Lisäksi työssä tutkittiin laminointiolosuhteiden vaikutusta lattialaminaatin käyristymään. Työn kirjallisuusosassa käsitellään lattialaminaatin valmistusta huomioiden ulkonäköön vaikuttavat tekijät sekä lattialaminaatin käyristymiseen vaikuttavia tekijöitä.Lattialaminaatin käyristymään vaikuttavat laminointiolosuhteet. Puulevyä vasten puristettavat kalvot kutistuvat laminoinnissa, erityisesti puristuslämpötilan kasvaessa. Laminaatin puristuksen jälkeinen käyristymä määräytyy lähinnä ylä- ja alapinnan kalvojen kutistuman erolla.Lattialaminaatin käyristymään varastoinnissa vaikuttaa ylä- ja alapinnan kalvojen dimensiostabiliteettikerroin. Yläpinnan kalvon dimensiostabiliteetti on huonompi kuin alapinnan, jolloin yläpinnan kalvo kutistuu enemmän kuivissa olosuhteissa käyristäen samalla laminaattia positiiviseen suuntaan.Taustapaperin ominaisuuksista merkittävimmin laminaatin käyristymään vaikuttaa kuituraaka-aine. Lattialaminaatin ulkonäköön vaikuttavat pinnassa olevat kuopat. Laminaatin taustan ulkonäköä voidaan parantaa lisäämällä taustapaperiin pehmitintä. Vääräntyyppisellä pehmittimellä menetetään taustan vastavetovoimaa.

Tuoreen sahatavaran mittavaihtelujen vaikutus sahauksen kannattavuuteen

Työn tavoitteena oli esittää tuoreen sahatavaran mittahajonnan merkitys sahaukselle. Lisäksi tutkittiin eri vuodenaikojen vaikutusta märkämitan hajontaan. Tutkimuksessa selvitettiin myös sahatavaran kuivauksen aikaisen kutistuman suuruutta ja hajontaa eri tilanteissa. Tutkimuksessa suoritettiin mittauksia kolmella eri sahalla n. 12 kk:n ajan. Näin saatiin tietoa eri vuodenaikojen vaikutuksesta märkämittojen hajontaan, ja sitä kautta sahauksen kannattavuuteen. Kuivauksen vaikutusta tuoremittojen ohjaukseen tutkittiin mittaamalla useita eri koe-eriä ennen ja jälkeen kuivauksen. Mittaustietojen avulla pystytään määrittämään todellinen tarvittava märkämitta, ja vältetään turhaa ylimittaa sahauksessa Tutkimus osoitti vuodenaikojen selvän merkityksen sahaushajontaan. Kuivauksen vaikutuksesta kappaleiden hajontaan saatiin tutkimuspohjaista, tarkkaa tietoa. Myös todellisesta kuivauskutistuman suuruudesta saatiin selkeä käsitys, joka helpottaa märkämitan, ja siten myös asiakkaalle menevän, todellisen sahatavaramitan määrittelyä.

Development of novel immunotherapies against bladder cancer

Le cancer de la vessie est le deuxième cancer urologique le plus fréquent dans le monde. La plupart des patients (75%) sont initialement diagnostiqués avec un cancer non musculo- invasif. Après résection trans-urétrale, ie traitement standard pour ce type de lésion chez les patients présentant un risque important de récidive/progression consiste en une série d'instillations intravésicales du Bacille de Calmette-Guerin (i.e. le vaccin BCG). Cependant cette "BCG thérapie" est associée à des effets secondaires non négligeables et s'avère inefficace dans 30% des cas, des limitations donc importantes qui soulignent la nécessité de développer des stratégies thérapeutiques alternatives. L'utilisation d'antigènes associés aux tumeurs (TAA) comme vaccin, combinée à une application locale d'immunostimulants sur le site tumoral, est une approche prometteuse en vue de maximiser les réponses immunitaires anti-tumorales localement. Nous montrons que la bactérie vivante atténuée Ty21a, issue du vaccin Vivotif® contre la fièvre typhoïde, peut être utilisée comme immunostimulant intravésical (IVES), mais ce uniquement dans le cas où la bactérie est en phase exponentielle de croissance (Vivotif exp). En effet, l'instillation IVES de Vivotif exp à la suite d'une vaccination par un TAA, un antigène mineur d'histocompatibilité mâle H-Y (Uty), permet d'augmenter de 15 fois le nombre de cellules T CD8 totales et spécifiques de l'antigène dans la vessie. Le recrutement des cellules T est TLR4-dépendent, ce qui suggère un rôle des lipopolysaccharides du Vivotif exp. Par ailleurs, en comparaison avec le contenu bactérien de la capsule de Vivotif, les bactéries en phase exponentielle de croissance permettent également une augmentation préférentielle des chemokines C5/C5a, CXCL1, CXCL2 et CXCL5 dans la vessie, mais pas du nombre de cellules T exprimant les récepteurs apparentés (C5aR et CXCR2). De plus, combiner la vaccination Uty avec le Vivotif exp en IVES permet d'améliorer la survie des souris présentant une tumeur orthotopique de la vessie exprimant l'antigène Uty (lignée tumorale murine MB49). Puisque pour certains cancers, aucun TAA - du moins exprimé à tous les stades tumoraux - n'est identifié, il est nécessaire de développer d'autres approches non vaccinales. Dans une deuxième partie de ce travail de thèse, nous avons donc investigué deux stratégies permettant d'induire une destruction des cellules tumorales, la thérapie génique par gène de suicide, d'une part, et la thérapie photodynamique dans le proche infrarouge (NIR-PDT), d'autre part. Pour appliquer ces thérapies, nous avons utilisé comme vecteur sûr et non toxique une forme non réplicative du virus du « Human Papillomavirus » (HPV) capable de "pseudo-infecter" préférentiellement les souris présentant des tumeurs vésicales (MB49). L'utilisation de pseudovirions (PsV) HPV portant comme gène suicide la thymidine kinase, une enzyme du virus de l'herpès simplex, suivi d'un traitement par la prodrogue Ganciclovir, permet de tuer 90% des cellules MB49 in-vitro ainsi que de ralentir significativement le développement des tumeurs vésicales in-vivo. Par ailleurs, l'emploi de particules pseudo- virales HPV couplées à la phtalocyanine IR700, un pigment photosensible présentant un pouvoir cytotoxique une fois activé, permet de tuer, après application d'une lumière dans le proche infrarouge, quasi 100% des cellules MB49 in-vitro et, plus important, de régresser des tumeurs in-vivo. De façon générale, ce travail de thèse présente des approches thérapeutiques innovantes et prometteuses pour le traitement des patients avec un cancer non musculo-invasif de la vessie. -- Bladder cancer is the second most common urological malignancy in the world. At initial diagnosis, non-muscle invasive bladder cancer (NMIBC) accounts for 75% of bladder cancer. The standard of care of NMIBC consists of intravesical (IVES) treatments with Bacillus- Calmette-Guerin (BCG) following transurethral resections of the lesions. However, repeated BCG treatments are associated with significant side effects and treatment failure may occur in 30% of the cases, underlying the necessity of alternative therapeutic strategies. The use of tumor-associated antigens (TAA) as vaccines followed by the local application of immunostimulants where the tumor resides is a promising approach to increase anti-tumor immune responses locally. We show that live attenuated Ty21a bacteria used from the vivotif® vaccine against typhoid fever can efficiently be used as IVES immunostimulant, only if bacteria are grown to exponential phase (Vivotif exp). In this condition, IVES immunostimulation after TAA vaccination with a minor histocompatibility male antigen HY (Uty) resulted in more than 15-fold increase of both vaccine-specific and total CD8-T cells in the bladder. T cell recruitment was mediated by TLR-4 suggesting that it was mainly mediated by lipopolysaccharides of Vivotif exp. In addition, these bacteria, as compared to the bacterial content of the vivotif capsule preferentially increased C5/C5a, CXCL1, CXCL2 and CXCL5 chemokines, but not the numbers of T cells expressing the cognate receptors (C5aR and CXCR2). Combination of IVES Vivotif exp with Uty vaccination improved survival of mice with pre-established orthotopic Uty-expressing MB49 murine bladder tumors, as compared to vaccination alone. As known TAA are not identified in all cancers, or not expressed in all stages of the tumor, we further investigated two potent approaches able of initiating tumor-cell destruction, suicide-gene therapy and near-infrared (NIR) photodynamic therapy (PDT). Towards a safe and non-toxic application of these therapies, we used Human Papillomavirus (HPV) replication-defective vectors that were able to preferentially pseudo-infect MB49-tumor bearing mice. HPV pseudovirions (PsV) carrying the Herpex-Simplex virus thymidine kinase suicide-gene followed by treatment with the prodrug Ganciclovir resulted in 90% of MB49 cell-death in-vitro and was able to significantly reduce bladder tumor growth in-vivo. Furthermore, HPV virus-like particles coupled to a NIR phtalocyanine dye, IR700 in combination with specific NIR light led to almost 100% of MB49 cell-death in-vitro and more interestingly, to bladder tumors shrinkage in-vivo. Overall, in this thesis, we offer promising therapeutic approaches for application in NMIBC patients.

Robust Estimates of the Negative Binomial Model

We consider robust parametric procedures for univariate discrete distributions, focusing on the negative binomial model. The procedures are based on three steps: ?First, a very robust, but possibly inefficient, estimate of the model parameters is computed. ?Second, this initial model is used to identify outliers, which are then removed from the sample. ?Third, a corrected maximum likelihood estimator is computed with the remaining observations. The final estimate inherits the breakdown point (bdp) of the initial one and its efficiency can be significantly higher. Analogous procedures were proposed in [1], [2], [5] for the continuous case. A comparison of the asymptotic bias of various estimates under point contamination points out the minimum Neyman's chi-squared disparity estimate as a good choice for the initial step. Various minimum disparity estimators were explored by Lindsay [4], who showed that the minimum Neyman's chi-squared estimate has a 50% bdp under point contamination; in addition, it is asymptotically fully efficient at the model. However, the finite sample efficiency of this estimate under the uncontaminated negative binomial model is usually much lower than 100% and the bias can be strong. We show that its performance can then be greatly improved using the three step procedure outlined above. In addition, we compare the final estimate with the procedure described in

Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis

Introduction: Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk. Material and Methods: We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998–2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously. Results: Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value#0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value$0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95%CI 1.05–1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation. Discussion: We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies.

Microwave spectrometry for the Evaluation of the structural integrity of metallic stents

Purpose: To assess the feasibility of a method based on microwave spectrometry to detect structural distortions of metallic stents in open air conditions and envisage the prospects of this approach toward possible medical applicability for the evaluation of implanted stents. Methods: Microwave absorbance spectra between 2.0 and 18.0 GHz were acquired in open air for the characterization of a set of commercial stents using a specifically design setup. Rotating each sample over 360º, 2D absorbance diagrams were generated as a function of frequency and rotation angle. To check our approach for detecting changes in stent length (fracture) and diameter (recoil), two specific tests were performed in open air. Finally, with a few adjustments, this same system provides 2D absorbance diagrams of stents immersed in a water-based phantom, this time over a bandwidth ranging from 0.2 to 1.8 GHz. Results: The authors show that metallic stents exhibit characteristic resonant frequencies in their microwave absorbance spectra in open air which depend on their length and, as a result, may reflect the occurrence of structural distortions. These resonances can be understood considering that such devices behave like dipole antennas in terms of microwave scattering. From fracture tests, the authors infer that microwave spectrometry provides signs of presence of Type I to Type IV stent fractures and allows in particular a quantitative evaluation of Type III and Type IV fractures. Recoil tests show that microwave spectrometry seems able to provide some quantitative assessment of diametrical shrinkage, but only if it involves longitudinal shortening. Finally, the authors observe that the resonant frequencies of stents placed inside the phantom shift down with respect to the corresponding open air frequencies, as it should be expected considering the increase of dielectric permittivity from air to water. Conclusions: The evaluation of stent resonant frequencies provided by microwave spectrometry allows detection and some quantitative assessment of stent fracture and recoil in open air conditions. Resonances of stents immersed in water can be also detected and their characteristic frequencies are in good agreement with theoretical estimates. Although these are promising results, further verifica tion in a more relevant phantom is required in order to foresee the real potential of this approach.

Should Koos I Vestibular Schwannomas Be Treated Early with Gamma Knife Surgery? A Prospective Series of 42 Consecutive Cases

Background: Gamma Knife surgery (GKS) for vestibular schwannomas (VS) has a long-term clinical and scientific track record. After a period of de-escalation of dose prescription, results show a high rate of tumor control with improvement of clinical outcome (less than 1% facial palsy, 50-70% hearing preservation). Currently, there is controversial data about the active early treatment of intracanalicular (Koos I) VS. Methods: We prospectively analyzed 208 VS, focusing on 42 Koos I patients treated with GKS as first intention in Lausanne University Hospital, between July 2010 and February 2015. We concentrated on patient, tumor, and dosimetric characteristics. Special attention was given on the dose to the cochlea and its impact in maintaining serviceable hearing. Results: The mean follow-up period was 1.7 years (range 0.6-4.2). Twenty-six (61.9%) were females and 16 (38.1%) males. Preoperative serviceable hearing was present in 33 (78.57%) patients. The mean maximal diameter was 7.7 (5-10). The median target volume at the moment of GKS was 90 mm3 (range 17-317). The median prescription isodose volume was 118 mm3 (range 37-603). The median marginal dose administrated was 12 Gy (range 11-12). The median number of shots was 2 (range 1-9). The median isodose prescription was 50% (range 45-80%). The median maximal dose received by the cochlea in patients in GR class 1 and 2 was 4.2 Gy (mean 4.4 Gy, range 1.8-7.6). Our preliminary results showed 98% tumor control, with 30% shrinkage on MRI. The actuarial probability of keeping the same audition class for those with functional hearing at GKS was 80% at 3 years; the probability of keeping a functional hearing was more than 90%. A paraclinical evolution (on MRI and/or audiometry) at the time diagnosis, before GKS, was associated with a less good prognosis (p < 0.05). Conclusions: Our preliminary data suggest that Koos I patients should be treated early with GKS, before tumor growth, and/or hearing deterioration, as they have the highest probability of hearing preservation. The results in terms of functional outcome seemed comparable to, or even better than, the other Koos classes (i.e., larger lesions).

Language extinction and linguistic fronts

Language diversity has become greatly endangered in the past centuries owing to processes of language shift from indigenous languages to other languages that are seen as socially and economically more advantageous, resulting in the death or doom of minority languages. In this paper, we define a new language competition model that can describe the historical decline of minority languages in competition with more advantageous languages. We then implement this non-spatial model as an interaction term in a reactiondiffusion system to model the evolution of the two competing languages. We use the results to estimate the speed at which the more advantageous language spreads geographically, resulting in the shrinkage of the area of dominance of the minority language. We compare the results from our model with the observed retreat in the area of influence of the Welsh language in the UK, obtaining a good agreement between the model and the observed data

Research networks and inventors’ mobility as drivers of innovation evidence from Europe

We investigate the importance of the labour mobility of inventors, as well as the scale, extent and density of their collaborative research networks, for regional innovation outcomes. To do so, we apply a knowledge production function framework at the regional level and include inventors’ networks and their labour mobility as regressors. Our empirical approach takes full account of spatial interactions by estimating a spatial lag model together, where necessary, with a spatial error model. In addition, standard errors are calculated using spatial heteroskedasticity and autocorrelation consistent estimators to ensure their robustness in the presence of spatial error autocorrelation and heteroskedasticity of unknown form. Our results point to the existence of a robust positive correlation between intraregional labour mobility and regional innovation, whilst the relationship with networks is less clear. However, networking across regions positively correlates with a region’s innovation intensity.

Example of Monte Carlo uncertainty assessment in the field of radionuclide metrology

This chapter presents possible uses and examples of Monte Carlo methods for the evaluation of uncertainties in the field of radionuclide metrology. The method is already well documented in GUM supplement 1, but here we present a more restrictive approach, where the quantities of interest calculated by the Monte Carlo method are estimators of the expectation and standard deviation of the measurand, and the Monte Carlo method is used to propagate the uncertainties of the input parameters through the measurement model. This approach is illustrated by an example of the activity calibration of a 103Pd source by liquid scintillation counting and the calculation of a linear regression on experimental data points. An electronic supplement presents some algorithms which may be used to generate random numbers with various statistical distributions, for the implementation of this Monte Carlo calculation method.

Clinical and biochemical responses after Gamma Knife surgery for a dopamine-secreting paraganglioma: case report.

The efficacy of Gamma Knife surgery (GKS) in local tumor control of non-secreting paragangliomas (PGLs) has been fully described by previous studies. However, with regard to secreting PGL, only one previous case report exists advocating its efficacy at a biological level. The aims of this study were: 1) to evaluate the safety/efficacy of GKS in a dopamine-secreting PGL; 2) to investigate whether the biological concentrations of free methoxytyramine could be used as a marker of treatment efficacy during the follow-up. We describe the case of a 62-year-old man diagnosed with left PGL. He initially underwent complete surgical excision. Thirty months after, he developed recurrent biological and neuroradiological disease; the most sensitive biomarker for monitoring the disease, concentration of plasma free methoxytyramine, started to increase. GKS was performed at a maximal marginal dose of 16 Gy. During the following 30 months, concentration of free methoxytyramine gradually decreased from 0.14 nmol/l (2*URL) before GKS to 0.09 nmol/l, 6 months after GKS and 0.07 nmol/l at the last follow-up after GKS (1.1*URL), confirming the efficacy of the treatment. Additionally, at 30 months there was approximately 36.6% shrinkage from the initial target volume. The GKS treatment was safe and effective, this being confirmed clinically, neuroradiologically and biologically. The case illustrates the importance of laboratory tests taking into account methoxytyramine when analyzing biological samples to assess the biochemical activity of a PGL. In addition, the identification of methoxytyramine as a unique positive biomarker could designate it for the monitoring of tumor relapse after treatments, including Gamma Knife surgery.

Human Capital Composition and Economic Growth at a Regional Level

With this paper we build a two-region model where both innovation and imitation are performed. In particular imitation takes the form of technological spillovers that lagging regions may exploit given certain human capital conditions. We show how the high skill content of each region’s workforce (rather than the average human capital stock) is crucial to determine convergence towards the income level of the leader region and to exploit the technological spillovers coming from the frontier. The same applies to bureaucratic/institutional quality which are conductive to higher growth in the long run. We test successfully our theoretical result over Spanish regions for the period between 1960 and 1997. We exploit system GMM estimators which allow us to correctly deal with endogeneity problems and small sample bias.

Performance persistence of equity funds in the Russian stock market

This thesis investigates performance persistence among the equity funds investing in Russia during 2003-2007. Fund performance is measured using several methods including the Jensen alpha, the Fama-French 3- factor alpha, the Sharpe ratio and two of its variations. Moreover, we apply the Bayesian shrinkage estimation in performance measurement and evaluate its usefulness compared with the OLS 3-factor alphas. The pattern of performance persistence is analyzed using the Spearman rank correlation test, cross-sectional regression analysis and stacked return time series. Empirical results indicate that the Bayesian shrinkage estimates may provide better and more accurate estimates of fund performance compared with the OLS 3-factor alphas. Secondly, based on the results it seems that the degree of performance persistence is strongly related to length of the observation period. For the full sample period the results show strong signs of performance reversal whereas for the subperiod analysis the results indicate performance persistence during the most recent years.