Coarse-Grained Model for Phospholipid/Cholesterol Bilayer

We construct a coarse-grained (CG) model for dipalmitoylphosphatidylcholine (DPPC)/cholesterol bilayers and apply it to large-scale simulation studies of lipid membranes. Our CG model is a two-dimensional representation of the membrane, where the individual lipid and sterol molecules are described by point-like particles. The effective intermolecular interactions used in the model are systematically derived from detailed atomic-scale molecular dynamics simulations using the Inverse Monte Carlo technique, which guarantees that the radial distribution properties of the CG model are consistent with those given by the corresponding atomistic system. We find that the coarse-grained model for the DPPC/cholesterol bilayer is substantially more efficient than atomistic models, providing a speed-up of approximately eight orders of magnitude. The results are in favor of formation of cholesterol-rich and cholesterol-poor domains at intermediate cholesterol concentrations, in agreement with the experimental phase diagram of the system. We also explore the limits of the novel coarse-grained model, and discuss the general validity and applicability of the present approach

Quantifying the Impact of Chikungunya and Dengue on Tourism Revenues

<b>Background</b><br> Health economists have traditionally quantified the burden of vector-borne diseases (such as chikungunya and dengue) as the sum of the cost of illness and the cost of intervention programmes. The objective of this paper is to predict the order of magnitude of possible reduction in tourism revenues if a major epidemic of chikungunya or dengue were to discourage visits by international tourists, and to prove that even a conservative estimate can be comparable to or even greater than the cost of illness and intervention programmes combined, and therefore should not be ignored in the estimation of the overall burden. <b>Methods</b><br> We have chosen three Asian economies where the immediate costs of these diseases have been recently calculated: Gujarat (an economically important state of India), Malaysia, and Thailand. Only international tourists from non-endemic countries have been considered to be discouraged, and a 4% annual decline in their numbers has been assumed. Revenues from these tourists have been calculated assuming that tourists from non-endemic countries would spend, on average, the same amount as all international tourists. These assumptions are conservative and consistent with the recent experience of Mauritius and R�union islands. Non-Resident Indians (NRIs) have been considered half as likely to avoid travel to Gujarat compared to non-Indians. This paper reports inflation-adjusted expenditure figures as 2008 US$, assuming recent market exchange rates of 42.0 INR/US$, 3.22 MYR/US$, 0.68 EUR/US$, and 33.6 THB/US$. <b>Findings</b><br> A 4$ 8 million for Gujarat, US$65 million for Malaysia, and US$ 363 million for Thailand. The estimated immediate annual cost of chikungunya and dengue to these economies is US$90 million, US$ 133 million, and approximately US$127 million respectively, indicating that impact on tourism revenues should not be ignored when calculating the burden of infectious diseases. The impact on Gujarat is relatively less because its share of world tourism receipts is just 0.04$ 9.6 million loss in domestic tourism revenues to Gujarat. <b>Interpretation</b><br> This paper shows that potential loss of tourism revenues due to a severe epidemic outbreak could be substantial. In some cases, ignoring this component could seriously underestimate cost-benefit results, forestalling promising interventions that could benefit the society as a whole or leading to inadequate investment of resources in prevention and public-funded control programmes. This would be to the detriment of especially poorer sections of the society, who may not be able to afford treatment costs. At present data are insufficient for us to make more than a preliminary estimate of the magnitude of the potential loss of revenues from tourism due to a major outbreak of chikungunya or dengue.

The risk of inguinal hernia repair after radical prostatectomy - a population-based cohort study

Objectives A nationwide population-based register study will evaluate the risk of postoperative inguinal hernia repair after primary curative-intent treatment of prostate carcinoma (PCa). Background Several previous studies have suggested an increased risk of inguinal hernia repair after prostatectomy. Only a few studies have compared the risk by PCa treatment modalities. Methods Data were collected between the years 1998 and 2016 from the national hospital discharge database HILMO and between the years 1998 and 2015 from the Finnish cancer registry to identify all men with prostate cancer with data on primary treatment available and information on inguinal hernia diagnoses and procedures among them. The risk of inguinal hernia repair among men managed with prostatectomy was compared to those treated with radiation therapy. Participants treated with prostatectomy were analyzed as a whole and separately stratified into subgroups managed with mini-invasive or open surgery. Multivariate Cox regression with adjustment for age and comorbidities was used for analysis. Results A total of 7207 cases of PCa were included in the study. 4595 men were treated with radical prostatectomy and 2612 with radiation therapy. Overall, the risk of hernia repair was higher among men treated with prostatectomy compared to men who received radiation therapy as the primary PCa treatment (HR 1.42, 95% CI 1.14-1.77). The risk did not differ markedly by the prostatectomy method. Conclusion Prostate cancer treatment with prostatectomy is associated with an increased risk of inguinal hernia surgery than external beam radiation therapy treatment. This risk should be taken into account when planning PCa treatment.Peer reviewe

The risk of inguinal hernia repair after radical prostatectomy - a population-based cohort study

Objectives A nationwide population-based register study will evaluate the risk of postoperative inguinal hernia repair after primary curative-intent treatment of prostate carcinoma (PCa). Background Several previous studies have suggested an increased risk of inguinal hernia repair after prostatectomy. Only a few studies have compared the risk by PCa treatment modalities. Methods Data were collected between the years 1998 and 2016 from the national hospital discharge database HILMO and between the years 1998 and 2015 from the Finnish cancer registry to identify all men with prostate cancer with data on primary treatment available and information on inguinal hernia diagnoses and procedures among them. The risk of inguinal hernia repair among men managed with prostatectomy was compared to those treated with radiation therapy. Participants treated with prostatectomy were analyzed as a whole and separately stratified into subgroups managed with mini-invasive or open surgery. Multivariate Cox regression with adjustment for age and comorbidities was used for analysis. Results A total of 7207 cases of PCa were included in the study. 4595 men were treated with radical prostatectomy and 2612 with radiation therapy. Overall, the risk of hernia repair was higher among men treated with prostatectomy compared to men who received radiation therapy as the primary PCa treatment (HR 1.42, 95% CI 1.14-1.77). The risk did not differ markedly by the prostatectomy method. Conclusion Prostate cancer treatment with prostatectomy is associated with an increased risk of inguinal hernia surgery than external beam radiation therapy treatment. This risk should be taken into account when planning PCa treatment.Peer reviewe

Systematic coarse-graining using structural information : applications to lipid membranes

Within last 20 years, advances in computational power and methodology have made computer simulations an integral part of studies of biomolecular systems. Simulations on all-atom level are routinely used to study, e.g., microscopic details of lipid aggregates and proteins. However, many phenomena are still outside the reach of all-atom simulations, and coarser models are needed. Detailed information from all-atom models can provide input data for parameterizing coarse-grained (CG) models. Techniques for such parameterization are called systematic coarse-graining methods, and can be based, e.g., on matching forces or structural information between the two resolutions. The main part of this dissertation employs inverse Monte Carlo (IMC) for constructing CG models for a lipid membrane containing dipalmitoylphosphatidylcholine (DPPC) and cholesterol. Three 2D models are constructed at different levels of resolution, in each case matching the radial distribution functions (RDFs) of the CG model to those from atom-scale simulations. The main results are the presence of cholesterol-rich and cholesterol-poor domains at intermediate cholesterol concentrations and the presence of strong tail density fluctuations at low cholesterol concentrations. The former agrees with the experimental studies of the system, while the latter was confirmed through atom-scale simulations. Accurate quantitative studies were restricted by transferability problems in all the CG models; hence, focus is on comparing the different models and critical discussion of the RDF inversion as a basis for coarse-graining. The IMC method is also improved by increasing its tolerance to statistical noise, as well as through inclusion of a virial pressure constraint and generalization to models where particles have internal degrees of freedom. The dissertation also discusses the analysis of individual lipid conformations from atom-scale simulations using self-organizing maps (SOMs), as well as the use of SOMs in coarse-graining. Atomistic simulations provide a vast amount of data, and direct analysis may be difficult. SOM, an unsupervised machine learning method, is studied as an alternative to more traditional analysis. Focus is on determining good parameters for the method and on qualitative analysis based on the good visualization properties of SOM. The internal dynamics of the molecules are also analyzed using SOMs for visualization. A bilayer of palmitoyllinoleoyl-PC (PLPC) is used as a model system

Analysis of phonation onsets in vowel production, using information from glottal area and flow estimate

A multichannel dataset comprising high-speed videoendoscopy images, and electroglottography and free-field microphone signals, was used to investigate phonation onsets in vowel production. Use of the multichannel data enabled simultaneous analysis of the two main aspects of phonation, glottal area, extracted from the high-speed videoendoscopy images, and glottal flow, estimated from the microphone signal using glottal inverse filtering. Pulse-wise parameterization of the glottal area and glottal flow indicate that there is no single dominant way to initiate quasi-stable phonation. The trajectories of fundamental frequency and normalized amplitude quotient, extracted from glottal area and estimated flow, may differ markedly during onsets. The location and steepness of the amplitude envelopes of the two signals were observed to be closely related, and quantitative analysis supported the hypothesis that glottal area and flow do not carry essentially different amplitude information during vowel onsets. Linear models were used to predict the phonation onset times from the characteristics of the subsequent steady phonation. The phonation onset time of glottal area was found to have good predictability from a combination of the fundamental frequency and the normalized amplitude quotient of the glottal flow, as well as the gender of the speaker. For the phonation onset time of glottal flow, the best linear model was obtained using the fundamental frequency and the normalized amplitude quotient of the glottal flow as predictors.Peer reviewe

Pelastustoiminnan tuloksellisuuden ja sen mittaamisen monitulkintaisuus

Pelastustoiminta on julkinen palvelu, jota ylläpidetään onnettomuuteen joutuneiden auttamiseksi ja onnettomuuksista aiheutuvien vahinkojen vähentämiseksi. Julkisin varoin toteutettujen palveluiden, myös pelastustoiminnan, pitäisi pystyä osoittamaan olevansa tuloksellista ja tuottavansa vastinetta verovaroille. Anniina Autero on tutkinut väitöskirjassaan pelastustoimen aiempaa tulostavoitetta palokuolemien lukumäärän vähentämisestä ja todennut tavoitteessa olevan monitulkintaisuutta. Tämä tutkimus selvittää, onko monitulkintaisuutta pelastustoiminnassa ja sen tulosmittaamisessa laajemminkin. Tutkimuksen teoreettisena viitekehyksenä ovat monitulkintaisuutta käsittelevän kirjallisuuden lisäksi muut pelastustoimintaan ja sen tuloksiin liittyvät aikaisemmat tutkimukset ja julkaisut. Tutkimusmenetelmänä on teemahaastattelu. Haastateltavina ovat pelastustehtävien lähtötilanteet ja toiminnan vaikutukset parhaiten havaitsevat paloesimiehet. Heidän näkemyksensä on järjestetty sisällönanalyysin menetelmällä ja verrattu kirjallisuudesta koottuihin näkökulmiin pelastustoiminnan tuloksellisuuden ilmenemisestä ja sen mittaamismahdollisuuksista. Lisäksi tutkimuksessa on kartoitettu nykyisin käytössä olevat ja aiemmat pelastustoiminnan tulosmittarit. Tutkimus osoittaa, että monitulkintaisuutta on paitsi julkisissa palveluissa ja palokuolemien lukumäärä -mittarissa, myös pelastustoiminnan tuloksissa ja niiden mittaamisessa. Tuloksia ei ole mahdollista määrittää yksiselitteisesti, eikä pelastustoiminta perustu aina kausaalisuuteen tapahtumaketjujen monimutkaisuuden ja monien vaikuttavien ympäristötekijöiden vuoksi. Lyhyt toimintavalmiusaika ei tarkoita aina hyvää lopputulosta, ja pelastustoiminta on voinut onnistua hyvin, vaikka kaikki tuhoutui. Nykyiset toimintavalmiusaikojen ja vahinkojen mittarit ovat monitulkintaisia, sillä niiden validiteetti, relevanssi ja reliabiliteetti ovat kyseenalaisia monien heikkouksien vuoksi. Toimintavalmiustavoitteiksi ei tulisi nähdä lähtö- ja ajoaikojen mittaamista vaan se toimintavalmius, joka muodostuu henkilöstön osaamisesta, asenteesta, ripeydestä ja yhteistyökyvystä, ja joka mahdollistetaan hyvällä kalustolla. Tiedostamalla monitulkintaisuus voidaan tuloksellisuusmittareiden kehitystyötä suunnata tunnuslukujen laskemisen sijaan sellaisten tavoitteiden määrittelyyn, joiden tavoittelu ohjaisi kohti parhaita toimintamalleja

Parameterization of a computational physical model for glottal flow using inverse filtering and high-speed videoendoscopy

High-speed videoendoscopy, glottal inverse filtering, and physical modeling can be used to obtain complementary information about speech production. In this study, the three methodologies are combined to pursue a better understanding of the relationship between the glottal air flow and glottal area. Simultaneously acquired high-speed video and glottal inverse filtering data from three male and three female speakers were used. Significant correlations were found between the quasi-open and quasi-speed quotients of the glottal area (extracted from the high-speed videos) and glottal flow (estimated using glottal inverse filtering), but only the quasi-open quotient relationship could be represented as a linear model. A simple physical glottal flow model with three different glottal geometries was optimized to match the data. The results indicate that glottal flow skewing can be modeled using an inertial vocal/subglottal tract load and that estimated inertia within the glottis is sensitive to the quality of the data. Parameter optimisation also appears to favour combining the simplest glottal geometry with viscous losses and the more complex glottal geometries with entrance/exit effects in the glottis.Peer reviewe