Browsing by Subject "CAUSALITY"

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  • Witjes, Julia J.; Smits, Loek P.; Pekmez, Ceyda T.; Prodan, Andrei; Meijnikman, Abraham S.; Troelstra, Marian A.; Bouter, Kristien E. C.; Herrema, Hilde; Levin, Evgeni; Holleboom, Adriaan G.; Winkelmeijer, Maaike; Beuers, Ulrich H.; van Lienden, Krijn; Aron-Wisnewky, Judith; Mannisto, Ville; Bergman, Jacques J.; Runge, Jurgen H.; Nederveen, Aart J.; Dragsted, Lars O.; Konstanti, Prokopis; Zoetendal, Erwin G.; de Vos, Willem; Verheij, Joanne; Groen, Albert K.; Nieuwdorp, Max (2020)
    The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of .Conclusion:Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.
  • Suotsalo, Kimmo; Xu, Yingying; Corander, Jukka; Pensar, Johan (2021)
    Learning vector autoregressive models from multivariate time series is conventionally approached through least squares or maximum likelihood estimation. These methods typically assume a fully connected model which provides no direct insight to the model structure and may lead to highly noisy estimates of the parameters. Because of these limitations, there has been an increasing interest towards methods that produce sparse estimates through penalized regression. However, such methods are computationally intensive and may become prohibitively time-consuming when the number of variables in the model increases. In this paper we adopt an approximate Bayesian approach to the learning problem by combining fractional marginal likelihood and pseudo-likelihood. We propose a novel method, PLVAR, that is both faster and produces more accurate estimates than the state-of-the-art methods based on penalized regression. We prove the consistency of the PLVAR estimator and demonstrate the attractive performance of the method on both simulated and real-world data.
  • DiNunno, Brandon S.; Grozdanov, Saso; Pedraza, Juan F.; Young, Steve (2017)
    In large-N-c conformal field theories with classical holographic duals, inverse coupling constant corrections are obtained by considering higher-derivative terms in the corresponding gravity theory. In this work, we use type IIB supergravity and bottom-up Gauss-Bonnet gravity to study the dynamics of boost-invariant Bjorken hydrodynamics at finite coupling. We analyze the time-dependent decay properties of non-local observables (scalar two-point functions and Wilson loops) probing the different models of Bjorken flow and show that they can be expressed generically in terms of a few field theory parameters. In addition, our computations provide an analytically quanti fiable probe of the coupling-dependent validity of hydrodynamics at early times in a simple model of heavyion collisions, which is an observable closely analogous to the hydrodynamization time of a quark-gluon plasma. We find that to third order in the hydrodynamic expansion, the convergence of hydrodynamics is improved and that generically, as expected from field theory considerations and recent holographic results, the applicability of hydrodynamics is delayed as the field theory coupling decreases.
  • Latvala, Antti; Ollikainen, Miina (2016)
    A study examining blood lipid traits takes epigenomics approaches to the next level by using carefully performed Mendelian randomization to assess causality rather than simply reporting associations.
  • Kaseva, Kaisa; Dobewall, Henrik; Yang, Xiaolin; Pulkki-Råback, Laura; Lipsanen, Jari; Hintsa, Taina; Hintsanen, Mirka; Puttonen, Sampsa; Hirvensalo, Mirja; Elovainio, Marko; Raitakari, Olli; Tammelin, Tuija (2019)
    Purpose: Physical activity, sleep problems, and symptoms of depression contribute to overall well-being. The factors are reciprocally associated, but the nature of these associations remains unclear. The present study examined whether sleep problems mediated the association between physical activity and depressive symptoms. Methods: The eligible population (n = 3596) consisted of adults from the ongoing, population-based Cardiovascular Risk in Young Finns Study started in 1980. Participants' leisure-time physical activity was assessed with physical activity index (2007) and sleep problems with Jenkins' Sleep Questionnaire in 2007 and 2011. Depressive symptoms were measured using modified Beck Depression Inventory in 2007 and 2012, from which the items reflecting sleep problems were excluded. Mediation analyses, through which the associations between the variables were examined, were adjusted for sex and a set of health-related covariates assessed in 2007 and 2011. Results: Physical activity was associated with decreased levels of sleep problems and depressive symptoms (P <0.05). The association between physical activity and depressive symptoms (b = -0.10, P <0.01) was partly mediated by sleep problems (proportion mediated = 0.36, P <0.01). The adjustment for depressive symptoms at baseline attenuated the mediation effect (proportion mediated = 0.30, P > 0.05). Conclusions: Physical activity's favorable contribution to depressive symptoms was mediated partly by sleep, but the mediation effect disappeared after adjusting for the previous depressive symptoms in adulthood.