Cost-effectiveness of early detection of breast cancer in Catalonia (Spain)

Background: Breast cancer (BC) causes more deaths than any other cancer among women in Catalonia. Early detection has contributed to the observed decline in BC mortality. However, there is debate on the optimal screening strategy. We performed an economic evaluation of 20 screening strategies taking into account the cost over time of screening and subsequent medical costs, including diagnostic confirmation, initial treatment, follow-up and advanced care. Methods: We used a probabilistic model to estimate the effect and costs over time of each scenario. The effect was measured as years of life (YL), quality-adjusted life years (QALY), and lives extended (LE). Costs of screening and treatment were obtained from the Early Detection Program and hospital databases of the IMAS-Hospital del Mar in Barcelona. The incremental cost-effectiveness ratio (ICER) was used to compare the relative costs and outcomes of different scenarios. Results: Strategies that start at ages 40 or 45 and end at 69 predominate when the effect is measured as YL or QALYs. Biennial strategies 50-69, 45-69 or annual 45-69, 40-69 and 40-74 were selected as cost-effective for both effect measures (YL or QALYs). The ICER increases considerably when moving from biennial to annual scenarios. Moving from no screening to biennial 50-69 years represented an ICER of 4,469€ per QALY. Conclusions: A reduced number of screening strategies have been selected for consideration by researchers, decision makers and policy planners. Mathematical models are useful to assess the impact and costs of BC screening in a specific geographical area.

Two component systems: physiological effect of a third component

Signal transduction systems mediate the response and adaptation of organisms to environmental changes. In prokaryotes, this signal transduction is often done through Two Component Systems (TCS). These TCS are phosphotransfer protein cascades, and in their prototypical form they are composed by a kinase that senses the environmental signals (SK) and by a response regulator (RR) that regulates the cellular response. This basic motif can be modified by the addition of a third protein that interacts either with the SK or the RR in a way that could change the dynamic response of the TCS module. In this work we aim at understanding the effect of such an additional protein (which we call ‘‘third component’’) on the functional properties of a prototypical TCS. To do so we build mathematical models of TCS with alternative designs for their interaction with that third component. These mathematical models are analyzed in order to identify the differences in dynamic behavior inherent to each design, with respect to functionally relevant properties such as sensitivity to changes in either the parameter values or the molecular concentrations, temporal responsiveness, possibility of multiple steady states, or stochastic fluctuations in the system. The differences are then correlated to the physiological requirements that impinge on the functioning of the TCS. This analysis sheds light on both, the dynamic behavior of synthetically designed TCS, and the conditions under which natural selection might favor each of the designs. We find that a third component that modulates SK activity increases the parameter space where a bistable response of the TCS module to signals is possible, if SK is monofunctional, but decreases it when the SK is bifunctional. The presence of a third component that modulates RR activity decreases the parameter space where a bistable response of the TCS module to signals is possible.

Contribution of early detection and adjuvant treatments to breast cancer mortality reduction in Catalonia, Spain

Background: Reductions in breast cancer (BC) mortality in Western countries have been attributed to the use of screening mammography and adjuvant treatments. The goal of this work was to analyze the contributions of both interventions to the decrease in BC mortality between 1975 and 2008 in Catalonia. Methodology/Principal Findings: A stochastic model was used to quantify the contribution of each intervention. Age standardized BC mortality rates for calendar years 1975-2008 were estimated in four hypothetical scenarios: 1) Only screening, 2) Only adjuvant treatment, 3) Both interventions, and 4) No intervention. For the 30-69 age group, observed Catalan BC mortality rates per 100,000 women-year rose from 29.4 in 1975 to 38.3 in 1993, and afterwards continuously decreased to 23.2 in 2008. If neither of the two interventions had been used, in 2008 the estimated BC mortality would have been 43.5, which, compared to the observed BC mortality rate, indicates a 46.7% reduction. In 2008 the reduction attributable to screening was 20.4%, to adjuvant treatments was 15.8% and to both interventions 34.1%. Conclusions/Significance: Screening and adjuvant treatments similarly contributed to reducing BC mortality in Catalonia. Mathematical models have been useful to assess the impact of interventions addressed to reduce BC mortality that occurred over nearly the same periods.

Mittausjärjestelmä IGBT:n lämpötilan määrittämiseen

Tässä diplomityössä tutustutaan IGBT:n ja tehodiodin rakenteisiin, lämmön muodostumiseen kyseisissä komponenteissa sekä menetelmiin, joilla komponenttien lämpötilat voidaan määrittää. Työssä suunnitellaan ja rakennetaan mittausjärjestelmä, jolla IGBT:n ja tehodiodin lämpötilat voidaan määrittää suoraan mittaamalla sekä matemaattisten mallien avulla. Mittausjärjestelmä koostuu DC-chopper -kytkennästä, kuormavirran, välipiirin jännitteen sekä lämpötilan mittauksista. Lämpötilan mittauksissa käytettiin komponenttien pintoihin liitettyjä termopareja. Matemaattisia malleja varten mittausjärjestelmään lisättiin välipiirin jännitteen sekä kuormavirran mittaus. Laitteiston ohjaus sekä mittaustulosten tallentaminen toteutettiin dSPACE -laitteistolla. Mittausjärjestelmän toimivuus testattiin Lappeenrannan teknillisen yliopiston Säätötekniikan laboratoriossa tehdyillä mittauksilla.

Jätevesilaitosten mallinnus

TäTässä työssä tarkastellaan jäteveden biologiseen puhdistukseen käytettävän aktiiviliete-prosessin kuvaamista matemaattisen mallintamisen avulla. Jäteveden puhdistus on jo vanha keksintö ja aktiivilieteprosessikin on otettu ensimmäisen kerran pilot- käyttöön vuonna 1914. Myös jätevesilaitosten matemaattinen mallintaminen on ollut pitkään tunnettu tekniikka ja ensimmäiset dynaamiset mallit kehitettiin 1950–luvulla. Työn alkuosassa on tarkasteltu jätevesilaitosten matemaattista mallintamista kirjallisuus-lähteiden pohjalta. Tarkastelun painopiste on suunnattu erilaisiin matemaattisiin malleihin ja mallintamisen kehitykseen. Mallintamisen ohessa on kiinnitetty huomiota aktiiviliete-prosessiin ja siihen vaikuttaviin tekijöihin. Mallintamiseen vaikuttavista tekijöistä erityistä huomiota on kiinnitetty ilmastukseen, bakteerien kasvuun ja selkeytykseen sekä niiden vaikutuksiin prosessin kannalta. Matemaattisen mallintamisen tarkastelun jälkeen työssä on pohdittu CFD–mallintamisen hyödyntämismahdollisuuksia aktiivilieteprosessien kuvaamisessa. Mallintamisosiossa on tarkasteltu Activated Sludge Model No. 3 (ASM 3) mallin rakennetta ja sisältöä sekä sen eri tekijöiden vaikutuksia malliin. Työn tässä osassa on tarkasteltu myös hapensiirtoa ilmastuksessa ilmakuplista veteen ja selkeytystä osana aktiivilieteprosessia. Tässä osiossa on käyty läpi myös kaikki prosessin kannalta oleelliset yhtälöt, esimerkiksi reaktionopeus- ja massataseyhtälöt.

Is the matching function Cobb-Douglas?

[cat] Estudiem les propietats teòriques que una funció d.emparellament ha de satisfer per tal de representar un mercat laboral amb friccions dins d'un model d'equilibri general amb emparellament aleatori. Analitzem el cas Cobb-Douglas, CES i altres formes funcionals per a la funció d.emparellament. Els nostres resultats estableixen restriccions sobre els paràmetres d'aquests formes funcionals per assegurar que l.equilibri és interior. Aquestes restriccions aporten raons teòriques per escollir entre diverses formes funcionals i permeten dissenyar tests d'error d'especificació de model en els treballs empírics.

Is the matching function Cobb-Douglas?

[cat] Estudiem les propietats teòriques que una funció d.emparellament ha de satisfer per tal de representar un mercat laboral amb friccions dins d'un model d'equilibri general amb emparellament aleatori. Analitzem el cas Cobb-Douglas, CES i altres formes funcionals per a la funció d.emparellament. Els nostres resultats estableixen restriccions sobre els paràmetres d'aquests formes funcionals per assegurar que l.equilibri és interior. Aquestes restriccions aporten raons teòriques per escollir entre diverses formes funcionals i permeten dissenyar tests d'error d'especificació de model en els treballs empírics.

Modelling the Evolution and Spread of HIV Immune Escape Mutants.

During infection with human immunodeficiency virus (HIV), immune pressure from cytotoxic T-lymphocytes (CTLs) selects for viral mutants that confer escape from CTL recognition. These escape variants can be transmitted between individuals where, depending upon their cost to viral fitness and the CTL responses made by the recipient, they may revert. The rates of within-host evolution and their concordant impact upon the rate of spread of escape mutants at the population level are uncertain. Here we present a mathematical model of within-host evolution of escape mutants, transmission of these variants between hosts and subsequent reversion in new hosts. The model is an extension of the well-known SI model of disease transmission and includes three further parameters that describe host immunogenetic heterogeneity and rates of within host viral evolution. We use the model to explain why some escape mutants appear to have stable prevalence whilst others are spreading through the population. Further, we use it to compare diverse datasets on CTL escape, highlighting where different sources agree or disagree on within-host evolutionary rates. The several dozen CTL epitopes we survey from HIV-1 gag, RT and nef reveal a relatively sedate rate of evolution with average rates of escape measured in years and reversion in decades. For many epitopes in HIV, occasional rapid within-host evolution is not reflected in fast evolution at the population level.

How to introduce connectance in a frame of an expression for diversity

Systems made of parts that are totally connected do not work, neither ecosys- tems nor artifacts. Relative connectance is inversely related to diversity, and both magnitudes can find a common frame of expression, in which some constant expressing the constraints of any organization might be embodied. If S is Simp- son's index, the expression (1 - S)IS as a measure of diversity offers some advantages or, at least, helps further reasoning. Such expression is the ratio between total interspecific possible interactions and possible intraspecific inter- actions.

Variación regional del coeficiente de atenuación de las ondas Rayleigh en el escudo europeo

A partir del análisis del modo fundamental de las ondas Rayleigh generadas por tres terremotos situados en las Azores, Sicilia y el Mar Negro se obtiene la variación regional del coeficiente de atenuación en el escudo europeo para un intervalo de periodos de 15-80 s. El método de análisis ha consistido en comparar los espectros de amplitudes observados con los calculados teóricamente. Para el calculo de estos últimos se ha utilizado un nuevo método consistente en calcular la función global de la fuente a partir de un proceso de mínimos cuadrados. Los resultados son los siguientes.

Lajittumisen dynamiikka epäpuhtauksien ja kuitujen painelajittelussa

Viimevuosina kuvantamistekniikat ovat kehittyneet huomattavasti. Näiden uusien tekniikoiden avulla voidaan tarkastella erilaisia prosesseja aiempaa tarkemmin. Painelajittelun teoriat perustuvat pääasiassa makrotason mittauksien pohjalta tehtyihin matemaattisiin malleihin, ja itse lajittumistapahtumaa ei ole aiemmin päästy kovinkaan tarkasti havainnoimaan. Tämän työn tavoitteena olikin selvittää lajittumistapahtumaa uuden kuvantamistekniikan avulla. Työn kirjallisuusosassa esiteltiin lyhyesti painelajitin ja sen toiminta. Myös painelajittelun perusteoriat käytiin lyhyesti läpi. Teoriaosan pääpaino oli lajittumistapahtumassa ja siihen vaikuttavissa tekijöissä. Lisäksi teoriaosassa esiteltiin teollisen painelajittelun nykytilannetta, työtä varten tehdyn esiselvityksen pohjalta. Lajitinsimulaattorikoeajoissa selvitettiin kuitujen ja roskapartikkelien käyttäyty-mistä painelajittimessa kuvantamisen avulla. Kuvauksissa keskityttiin rakosihdin raon tapahtumiin, sekä sihtipinnan tapahtumiin. Kuvamateriaalista laskettiin kuitujen ja roskien liikenopeuksia lankasihtiprofiilin raossa, sekä sihdin pinnalla. Lisäksi tutkittiin kehänopeuden, tuotannon ja sakeuden vaikutusta liike-nopeuksiin. Kuvamateriaalista pyrittiin myös havainnoimaan mahdollista kuitujen takaisinvirtausta. Kuvantamisella saatiin uutta tietoa kuitujen ja roskapartikkelien liikkeestä painelajittimessa. Tuloksista kävi muun muassa ilmi, että roottorin elementin pienimmän välyksen kohdalla akseptoituu huomattava määrä massaa. Tämä selittyy sillä, että pienimmän välyksen kohta tuottaa huomattavan positiivisen painepulssin. Kuitujen ja roskapartikkelien nopeudet raossa noudattelivat muutenkin hyvin selkeästi elementin tuottamaa painepulssia. Lisäksi kuvamateriaalista havaittiin, että sihdin raon suulle kertyy profiilin korkuinen kuituflokki. Koko sihdin peittävää kuitumattoa ei havaittu.

Anàlisis del modelo de la telaraña en contexto de incertidumbre

In the present work the behavior of a model acquaintance of market is analyzed with an only one, in that is considered that the parameters that tie the variables that it incorporates the pattern come expressed through uncertain magnitudes. The objective of the study consists on the analysis of the balance from the hypotheses of established uncertainties

Movilidad intergeneracional y emparejamiento selectivo en España

This paper examines the role of assortative mating in the intergenerational economic mobility in Spain. Sons and daughters usually marry individuals with similar characteristics, which may lower mobility. Our empirical strategy employs the Two-sample two-stage least squares estimator to estimate the intergenerational income elasticity in absence of data for two generations not residing in the same household. Our findings suggest that assortative mating plays an important role in the intergenerational transmission process. On average about 50 per 100 of the covariance between parents’ income and child family’s incomecan be accounted for by the person the child is married to

Progress in front propagation research

We review the progress in the field of front propagation in recent years. We survey many physical, biophysical and cross-disciplinary applications, including reduced-variable models of combustion flames, Reid's paradox of rapid forest range expansions, the European colonization of North America during the 19th century, the Neolithic transition in Europe from 13 000 to 5000 years ago, the description of subsistence boundaries, the formation of cultural boundaries, the spread of genetic mutations, theory and experiments on virus infections, models of cancer tumors, etc. Recent theoretical advances are unified in a single framework, encompassing very diverse systems such as those with biased random walks, distributed delays, sequential reaction and dispersion, cohabitation models, age structure and systems with several interacting species. Directions for future progress are outlined

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