Effects of particulate matters on inflammatory markers in the general adult population

Summary: Particulate air pollution is associated with increased cardiovascular risk. The induction of systemic inflammation following particle inhalation represents a plausible mechanistic pathway. The purpose of this study was to assess the associations of short-term exposure to ambient particulate matters of aerodynamic diameter less than 10 μm (PM10) with circulating inflammatory markers in 6183 adults in Lausanne, Switzerland. The results show that short-term exposure to PM10 was associated with higher levels of circulating IL-6 and TNF-α. The positive association of PM10 with markers of systemic inflammation materializes the link between air pollution and cardiovascular risk. Background: Variations in short-term exposure to particulate matters (PM) have been repeatedly associated with daily all-cause mortality. Particle-induced inflammation has been postulated to be one of the important mechanisms for increased cardiovascular risk. Experimental in-vitro, in-vivo and controlled human studies suggest that interleukin 6 (IL-6) and tumor-necrosis-factor alpha (TNF-α) could represent key mediators of the inflammatory response to PM. The associations of short-term exposure to ambient PM with circulating inflammatory markers have been inconsistent in studies including specific subgroups so far. The epidemiological evidence linking short-term exposure to ambient PM and systemic inflammation in the general population is scarce. So far, large-scale population-based studies have not explored important inflammatory markers such as IL-6, IL-1β or TNF-α. We therefore analyzed the associations between short-term exposure to ambient PM10 and circulating levels of high-sensitive CRP (hs-CRP), IL-6, IL-1β and TNF-α in the population-based CoLaus study. Objectives: To assess the associations of short-term exposure to ambient particulate matters of aerodynamic diameter less than 10 μm (PM10) with circulating inflammatory markers, including hs-CRP, IL-6, IL-1β and TNF-α, in adults aged 35 to 75 years from the general population. Methodology: All study subjects were participants to the CoLaus study (www.colaus.ch) and the baseline examination was carried out from 2003 to 2006. Overall, 6184 participants were included. For the present analysis, 6183 participants had data on at least one of the four measured circulating inflammatory markers. The monitoring data was obtained from the website of Swiss National Air Pollution Monitoring Network (NABEL). We analyzed data on PM10 as well as outside air temperature, pressure and humidity. Hourly concentrations of PM10 were collected from 1 January 2003 to 31 December 2006. Robust linear regression (PROC ROBUSTREG) was used to evaluate the relationship between cytokine inflammatory and PM10. We adjusted all analyses for age, sex, body mass index, smoking status, alcohol consumption, diabetes status, hypertension status, education levels, zip code, and statin intake. All data were adjusted for the effects of weather by including temperature, barometric pressure, and season as covariates in the adjusted models. We performed simple and multiple logistic regression analyses. Descriptive statistical analysis used the Wilcoxon rank sum test (for medians). All data analyses were performed using SAS software (version 9.2; SAS Institute Inc., Cary, NC, USA), and a two-sided significance level of 5% was used. Results: PM10 levels averaged over 24 hours were significantly and positively associated with continuous IL-6 and TNF-α levels, in the whole study population both in unadjusted and adjusted analyses. For each cytokine, there was a similar seasonal pattern, with wider confidence intervals in summer than during the other seasons, which might partly be due to the smaller number of participants examined in summer. The associations of PM10 with IL-6 and TNF-α were also found after having dichotomized these cytokines into high versus low levels, which suggests that the associations of PM10 with the continuous cytokine levels are very robust to any distributional assumption and to potential outlier values. In contrast with what we observed for continuous IL-1β levels, high PM10 levels were significantly associated with high IL-1β. PM10 was significantly associated with IL-6 and TNF-α in men, but with TNF-α only in women. However, there was no significant statistical interaction between PM10 and sex. For IL-6 and TNF-α, the associations tended to be stronger in younger people, with a significant interaction between PM10 and age groups for IL-6. PM10 was significantly associated with IL-6 and TNF-α in the healthy group and also in the "non-healthy" group, although the statistical interaction between healthy status and PM10 was not significant. Conclusion: In summary, we found significant independent positive associations of short-term exposure to PM10 with circulating levels of IL-6 and TNF-α in the adult population of Lausanne. Our findings strongly support the idea that short-term exposure to PM10 is sufficient to induce systemic inflammation on a broad scale in the general population. From a public health perspective, the reported association of elevated inflammatory cytokines with short-term exposure to PM10 in a city with relatively clean air such as Lausanne supports the importance of limiting urban air pollution levels.

Confirmation of persistent radio jets in the microquasar LS 5039

We present here new observations conducted with the EVN and MERLIN of the persistent microquasar LS 5039 discovered by Paredes et al. (2000) with the VLBA. The new observations confirm the presence of an asymmetric two-sided jet reaching up to 1000 AU on the longest jet arm. The results suggest a bending of the jets with increasing distance from the core and/or precession. The origin and location of the high-energy gamma-ray emission associated with the system is discussed and an estimate of the magnetic field at the base of the jet given. Our results suggest a well collimated radio jet. We also comment on new observing strategies to be used with satellites and forthcoming detectors, since this persistent source appears to be a rather good laboratory to explore the accretion/ejection processes taking place near compact objects.

EVN+MERLIN observations of microquasar candidates at low galactic latitudes

In an attempt to increase the number of known microquasars, Paredes et al. (2002) have presented a long-term project focused on the search for new objects of this type. They performed a cross-identification between X-ray and radio catalogs under very restrictive selection criteria for sources with |b|<5 degrees, and obtained a sample of 13 radio-emitting X-ray sources. Follow-up observations of 6 of these sources with the VLA provided accurate coordinates, which were used to discover optical counterparts for all of them. We have observed these six sources with the EVN and MERLIN at 5 GHz. Five of the six objects have been detected and imaged, presenting different morphologies: one source has a two-sided jet, three sources have one-sided jets, and one source is compact. With all the presently available information, we conclude that two of the sources are promising microquasar candidates in our Galaxy.

Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

BACKGROUND: Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. METHODS: In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. RESULTS: We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). CONCLUSIONS: After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders.

Platform pricing and consumer foresight: The case of airports

Airports have become platforms that derive revenues from both aeronautical and commercial activities. The demand for these services is characterized by a one-way complementarity in that only air travelers can purchase retail goods at the airport terminals. We analyze a model of optimal airport behavior in which this one-way complementarity is subject to consumer foresight, i.e., consumers may not anticipate in full the ex post retail surplus when purchasing a flight ticket. An airport sets landing fees, and, in addition, also chooses the retail market structure by selecting the number of retail concessions to be awarded. We find that, with perfectly myopic consumers, the airport chooses to attract more passengers via low landing fees, and also sets the minimum possible number of retailers in order to increase the concessions’ revenues, from which it obtains the largest share of profits. However, even a very small amount of anticipation of the consumer surplus from retail activities changes significantly the airport’s choices: the optimal airport policy is dependent on the degree of differentiation in the retail market. When consumers instead have perfect foresight, the airport establishes a very competitive retail market, where consumers enjoy a large surplus. This attracts passengers and it is exploited by the airport by charging higher landing fees, which then constitute the largest share of its profits. Overall, the airport’s profits are maximal when consumers have perfect foresight. Keywords: two-sided markets, platform pricing, one-way demand complementarity, consumer foresight. JEL classification: L1, L2, L93.

In Google we trust?

In a micro-founded model, we derive novel incentives for a monopoly search engine to distort its organic and its sponsored results on searches for online content and offline products. Distorting organic results towards content publishers with less effective display advertising and/or distorting sponsored results towards higher margin merchants (by underweighting consumer relevance in search auctions) increase per capita revenues but lower participation. The interplay of these incentives determines search bias and welfare. We also characterize how the welfare consequences of integration into display advertising, as intermediary or publisher, depend on asymmetries, monopolization and targeting.

Pienahitsin sijainnin vaikutus kuormaa kantamattoman T-liitoksen väsymiskestävyyteen

Hitsatuissa rakenteissa on paljon hitsien aiheuttamia epäjatkuvuuskohtia, jotka ovat alttiita vaurioitumaan väsyttävän kuormituksen alaisina. Standardit ja normit auttavat suunnittelua rakenneyksityiskohtien analysoinnissa, mutta ohjeiden arvot vaihtelevat paljon. Onkin tär-keää päättää, mitä standardia tai normia käytetään ja saada tutkimustuloksia tukemaan ohjeen käyttöä. Tämä työ on tehty Konecranes Finland Oy:lle. Työn tarkoituksena on etsiä käytössä olevi-en ohjeiden joukosta suunnittelun kannalta parhaiten todellista rakennetta kuvaava. Työssä esitellään käytössä olevia standardeja ja normeja sekä vertaillaan niiden välisiä eroja rakenneyksityiskohdan väsymiskestävyyden määrittämisessä. Työssä tarkastellaan myös hitsatun rakenteen väsymiseen vaikuttavia tekijöitä sekä väsymisanalyysissä käytet-täviä menetelmiä. Tutkittavaan liitokseen valittiin kolme erilaista hitsiä, yksi –ja kaksipuolinen pienahitsi sekä katkopienahitsi. Elementtimenetelmän avulla luotiin malleja koekappaleista ja laskettiin niille väsymiskestävyydet. Tämä lisäksi väsymistä tarkasteltiin väsytyskokeilla, jotka suoritti Lappeenrannan Teknillisen Yliopiston Teräsrakenteiden laboratorio. Lopputuloksena työstä saatiin tietoa hitsien väsymiskestävyyksistä. Liitosten väsymiskes-tävyydet olivat hyviä ja varsinkin katkopienahitsin tulokset olivat odotettua paremmat. Kat-kopienahitsin väsymiskestävyys vaatii tämän työn tulosten perusteella lisää tutkimista.

Epäsuoran kysyntätiedon hyödyntäminen verkkokaupan tuotevalikoima- ja hinnoittelupäätöksissä

Tässä diplomityössä tutkitaan, miten verkkokaupan kävijävirran käyttäytymistä analysoimalla voidaan tehdä perusteltuja, tarkoituksenmukaisiin nimikkeisiin ja niiden parametreihin kohdistuvia päätöksiä tilanteessa, jossa laajamittaisemmat historiatiedot toteutuneesta myynnistä puuttuvat. Teoriakatsauksen perusteella muodostettiin ratkaisumalli, joka perustuu potentiaalisten kysyntäajurien muodostamiseen ja testaamiseen. Testisarjan perusteella valittavaa ajuria käytetään estimoimaan nimikkeiden kysyntää, jolloin sitä voidaan käyttää toteutuneen myynnin sijasta esimerkiksi Pareto-analyysissä. Näin huomio on mahdollista keskittää rajattuun määrään merkitykseltään suuria nimikkeitä ja niiden yksityiskohtaisiin parametreihin, joilla on merkitystä asiakkaan ostopäätöstilanteissa. Lisäksi voidaan tunnistaa nimikkeitä, joiden ongelmana on joko huono verkkonäkyvyys tai yhteensopimattomuus asiakastarpeiden kanssa. Ajurien testaamisperiaatteena käytetään kertymäfunktioiden yhdenmukaisuustarkastelua, joka rakentuu kolmesta peräkkäisestä vaiheesta; visuaalisesta tarkastelusta, kahden otoksen 2-suuntaisesta Kolmogorov-Smirnov-yhteensopivuustestistä ja Pearsonin korrelaatiotestistä. Mallia ja sen avulla tuotettua kysynnän ajuria testattiin veneilyalan kuluttaja-asiakkaille suunnatussa verkkokaupassa, jossa sillä tunnistettiin Pareto-jakauman alkupäästä runsaasti nimikkeitä, joiden parametreissa oli myynnin kannalta epäedullisia tekijöitä. Jakauman toisessa päässä tunnistettiin satoja nimikkeitä, joiden ongelmana on ilmeisesti joko huono verkkonäkyvyys tai nimikkeiden yhteensopimattomuus asiakastarpeiden kanssa.

Letters from the War of Ecosystems – An Analysis of Independent Software Vendors in Mobile Application Marketplaces

The recent emergence of a new generation of mobile application marketplaces has changed the business in the mobile ecosystems. The marketplaces have gathered over a million applications by hundreds of thousands of application developers and publishers. Thus, software ecosystems—consisting of developers, consumers and the orchestrator—have emerged as a part of the mobile ecosystem. This dissertation addresses the new challenges faced by mobile application developers in the new ecosystems through empirical methods. By using the theories of two-sided markets and business ecosystems as the basis, the thesis assesses monetization and value creation in the market as well as the impact of electronic Word-of-Mouth (eWOM) and developer multihoming— i. e. contributing for more than one platform—in the ecosystems. The data for the study was collected with web crawling from the three biggest marketplaces: Apple App Store, Google Play and Windows Phone Store. The dissertation consists of six individual articles. The results of the studies show a gap in monetization among the studied applications, while a majority of applications are produced by small or micro-enterprises. The study finds only weak support for the impact of eWOM on the sales of an application in the studied ecosystem. Finally, the study reveals a clear difference in the multi-homing rates between the top application developers and the rest. This has, as discussed in the thesis, an impact on the future market analyses—it seems that the smart device market can sustain several parallel application marketplaces.

Congenital ventricular septal defects and prenatal exposure to cyclooxygenase inhibitors

Ventricular septal defects (VSDs) are common congenital abnormalities which have been reported to be associated with maternal fever and various environmental factors. The aim of the present study was to evaluate the effect of prenatal exposure to cyclooxygenase (COX) inhibitors on heart defects. A retrospective statistical analysis was performed using data collected in our laboratory during various teratological studies carried out on albino CRL:(WI)WUBR Wistar strain rats from 1997 to 2004. The observations were compared with concurrent and historic control data, as well as findings from other developmental toxicological studies with selective and nonselective COX-2 inhibitors. Despite the lack of significant differences in the frequency of VSDs between drug-exposed and control groups, statistical analysis by the two-sided Mantel-Haenszel test and historical control data showed a higher incidence of heart defects in offspring exposed to nonselective COX inhibitors (30.06/10,000). Unlike other specific inhibitors, aspirin (46.26/10,000) and ibuprofen (106.95/10,000) significantly increased the incidence of the VSD when compared with various control groups (5.38-19.72/10,000). No significant differences in length or weight were detected between fetuses exposed to COX inhibitors and born with VSD and non-malformed offsprings. However, a statistically significant increase of fetal body length and decrease of body mass index were found in fetuses exposed to COX inhibitors when compared with untreated control. We conclude that prenatal exposure to COX inhibitors, especially aspirin and ibuprofen, increased the incidence of VSDs in rat offspring but was not related to fetal growth retardation.

The effect of 677C>T and 1298A>C MTHFR polymorphisms on sulfasalazine treatment outcome in rheumatoid arthritis

Despite the availability of several new agents for the treatment of rheumatoid arthritis (RA), sulfasalazine remains the mainstay because of both cost and experience with its use. Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and several polymorphisms have been described in the MTHFR gene. Of these, the 677C>T and 1298A>C polymorphisms have been associated with altered enzyme activity. To examine the association between 677C>T and 1298A>C MTHFR polymorphisms and sulfasalazine efficacy for the treatment of RA, a total of 117 RA patients treated with sulfasalazine (1 g daily; duration of treatment 17 ± 5 months) were analyzed. The 677C>T and 1298 A>C polymorphisms were detected using a PCR-RFLP method. RA was diagnosed according to the criteria of the American College of Rheumatology (ACR). The remission of RA symptoms was evaluated according to the ACR 20% response criteria. Allele and genotype frequencies were compared by the two-sided Fisher exact test. The frequency of remission was 47.2% and 44.6% in carriers of 677T and 1298C alleles, compared to 40.7% and 42.0% in carriers of 677C and 1298A alleles, respectively. These differences were statistically non-significant. When the multivariate analysis was additionally adjusted for patients’ age, gender and RA duration, the association of the MTHFR 677T allele with increased frequency of remission was statistically significant. Although RA remission rate in carriers of the MTHFR 677T and 1298C alleles was more frequently observed, it does not seem that 677C>T and 1298A>C MTHFR polymorphisms have a major influence on treatment outcome in RA patients treated with sulfasalazine.

Kommunikaatio-operaattorin taloudellisesti kannattava liiketoimintamalli tasapuolisen pääsyn FTTH-verkkoihin

FTTH-liityntäverkkoja voivat rakennuttaa ja omistaa perinteisten teleoperaattoreiden lisäksi myös muut toimijat, kuten sähköyhtiöt, valtion- ja kuntien omistamat yhtiöt ja yksityiset osuuskunnat. Markkinatoimijoiden ja eri teknologioiden keskinäinen kilpailu johtaa kuitenkin helposti pieniin liityntätiheyksiin ja hajanaisiin pieniin verkkoihin. Tämä tekee verkkojen kannattavasta rakentamisesta vaikeaa ja palvelujen toteuttamisesta tehotonta. Tilannetta voidaan parantaa tasapuolisella pääsyllä, joka selkeyttää arvoketjun osapuolten rooleja. Diplomityön tavoitteena oli kuvata kommunikaatio-operaattorin rooli Suomen telemarkkinaan ja rakentaa sille taloudellisesti kannattava liiketoimintamalli toisen osapuolen toteuttamiin tasapuolisen pääsyn FTTH-verkkoihin. Työ toteutettiin hyödyntäen konstruktiivista tutkimusotetta ja sen lopputuloksena syntyi soveltuva liiketoimintamalli. Kommunikaatio-operaattorin kaksipuolisella alustalla yhdistetään valtakunnallisesti toisiinsa palveluntarjoajat ja alueellisiin liityntäverkkoihin liittyneet loppuasiakkaat. Kommunikaatio-operaattorin liiketoimintamalli mahdollistaa kapasiteetin, palvelunlaadun ja toimintavarmuuden suhteen erilaistetut virtuaaliset tukkutuotteet ja sitä kautta mahdollisuuden uuteen ansaintaan.

Coopetition as a lead generating mechanism: design, modelling and simulation

The aim of this research is to develop a tool that could allow to organize coopetitional relationships between organizations on the basis of two-sided Internet platform. The main result of current master thesis is a detailed description of the concept of the lead generating internet platform-based coopetition. With the tools of agent-based modelling and simulation, there were obtained results that could be used as a base for suggestion that the developed concept is able to cause a positive effect on some particular industries (e.g. web-design studios market) and potentially can bring some benefits and extra profitability for most companies that operate on this particular industry. Also on the basis of the results it can be assumed that the developed instrument is also able to increase the degree of transparency of the market to which it is applied.

On the Political Economy of Sequential Reforms

This paper proposes an explanation for why efficient reforms are not carried out when losers have the power to block their implementation, even though compensating them is feasible. We construct a signaling model with two-sided incomplete information in which a government faces the task of sequentially implementing two reforms by bargaining with interest groups. The organization of interest groups is endogenous. Compensations are distortionary and government types differ in the concern about distortions. We show that, when compensations are allowed to be informative about the government’s type, there is a bias against the payment of compensations and the implementation of reforms. This is because paying high compensations today provides incentives for some interest groups to organize and oppose subsequent reforms with the only purpose of receiving a transfer. By paying lower compensations, governments attempt to prevent such interest groups from organizing. However, this comes at the cost of reforms being blocked by interest groups with relatively high losses.

Contentious Contracts

This paper offers an explanation of rationally contracts where incompeteness refers to unforeseen contingencies. Agents enter a relationship with two-sided moral hazard in which a commitment to discard parts of the joint resources may be ex ante efficient.