| 2741. |
- Hieronymus, Fredrik, et al.
(författare)
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Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression.
- 2016
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 21:4, s. 523-30
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Tidskriftsartikel (refereegranskat)abstract
- The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo. Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter. In this study, we examined whether the negative outcomes of many SSRI trials may be partly caused by the use of this frequently questioned measure of response. We undertook patient-level post-hoc analyses of 18 industry-sponsored placebo-controlled trials regarding paroxetine, citalopram, sertraline or fluoxetine, and including in total 6669 adults with major depression, the aim being to assess what the outcome would have been if the single item depressed mood (rated 0-4) had been used as a measure of efficacy. In total, 32 drug-placebo comparisons were reassessed. While 18 out of 32 comparisons (56%) failed to separate active drug from placebo at week 6 with respect to reduction in HDRS-17-sum, only 3 out of 32 comparisons (9%) were negative when depressed mood was used as an effect parameter (P<0.001). The observation that 29 out of 32 comparisons detected an antidepressant signal from the tested SSRI suggests the effect of these drugs to be more consistent across trials than previously assumed. Further, the frequent use of the HDRS-17-sum as an effect parameter may have distorted the current view on the usefulness of SSRIs and hampered the development of novel antidepressants.Molecular Psychiatry advance online publication, 28 April 2015; doi:10.1038/mp.2015.53.
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| 2742. |
- Hieronymus, Fredrik, et al.
(författare)
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Efficacy of selective serotonin reuptake inhibitors in the absence of side effects: a mega-analysis of citalopram and paroxetine in adult depression
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 23:8, s. 1731-1736
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that the superiority of antidepressants over placebo in controlled trials is merely a consequence of side effects enhancing the expectation of improvement by making the patient realize that he/she is not on placebo. We explored this hypothesis in a patient-level post hoc-analysis including all industry-sponsored, Food and Drug Administration-registered placebo-controlled trials of citalopram or paroxetine in adult major depression that used the Hamilton Depression Rating Scale (HDRS) and included a week 6 symptom assessment (n=15). The primary analyses, which compared completers on active treatment without early adverse events to completers on placebo (with or without adverse events) with respect to reduction in the HDRS depressed mood item showed larger symptom reduction in patients given active treatment, the effect sizes being 0.48 for citalopram and 0.33 for paroxetine. In actively treated subjects reporting early adverse events, who also outperformed those given placebo, the severity of the adverse events did not predict response. Several sensitivity analyses, for example, including (i) those using change of the sum of all HDRS-17 items as effect parameter, (ii) those excluding all subjects with adverse events (that is, also those on placebo) and (iii) those based on the intention-to-treat population, were all in line with the primary analyses. The finding that both paroxetine and citalopram are clearly superior to placebo also when not producing adverse events, as well as the lack of association between adverse event severity and response, argue against the theory that antidepressants outperform placebo solely or largely because of their side effects.
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| 2743. |
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| 2744. |
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| 2745. |
- Hietala, Linnea, 1988
(författare)
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Exact results for the six-vertex model with domain wall boundary conditions and a partially reflecting end
- 2022
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Ingår i: Letters in Mathematical Physics. - : Springer Science and Business Media LLC. - 0377-9017 .- 1573-0530. ; 112:2
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Tidskriftsartikel (refereegranskat)abstract
- The trigonometric six-vertex model with domain wall boundary conditions and one partially reflecting end on a lattice of size 2n x m, m <= n, is considered. The partition function is computed using the Izergin-Korepin method, generalizing the result of Foda and Zarembo from the rational to the trigonometric case. Thereafter, we specify the parameters in Kuperberg's way to get a formula for the number of states as a determinant of Wilson polynomials. We relate this to a new type of alternating sign matrices, similar to how the six-vertex model with domain wall boundary conditions is related to normal alternating sign matrices. In an appendix, we compute the partition function again, showing that it is also possible to find it with the method of Foda and Wheeler.
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| 2746. |
- Hildeman, Anders, 1984, et al.
(författare)
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Deformed SPDE models with an application to spatial modeling of significant wave height
- 2021
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Ingår i: Spatial Statistics. - : Elsevier BV. - 2211-6753. ; 42
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Tidskriftsartikel (refereegranskat)abstract
- A non-stationary Gaussian random field model is developed based on a combination of the stochastic partial differential equation (SPDE) approach and the classical deformation method. With the deformation method, a stationary field is defined on a domain which is deformed so that the field becomes non-stationary. We show that if the stationary field is a Matérn field defined as a solution to a fractional SPDE, the resulting non-stationary model can be represented as the solution to another fractional SPDE on the deformed domain. By defining the model in this way, the computational advantages of the SPDE approach can be combined with the deformation method's more intuitive parameterization of non-stationarity. In particular it allows for independent control over the non-stationary practical correlation range and the variance, which has not been possible with previously proposed non-stationary SPDE models. The model is tested on spatial data of significant wave height, a characteristic of ocean surface conditions which is important when estimating the wear and risks associated with a planned journey of a ship. The model parameters are estimated to data from the north Atlantic using a maximum likelihood approach. The fitted model is used to compute wave height exceedance probabilities and the distribution of accumulated fatigue damage for ships traveling a popular shipping route. The model results agree well with the data, indicating that the model could be used for route optimization in naval logistics.
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| 2747. |
- Hildeman, Anders, 1984, et al.
(författare)
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Joint spatial modeling of significant wave height and wave period using the SPDE approach
- 2022
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Ingår i: Probabilistic Engineering Mechanics. - : Elsevier BV. - 0266-8920 .- 1878-4275. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- The ocean wave distribution in a specific region of space and time is described by its sea state. Knowledge about the sea states a ship encounters on a journey can be used to assess various parameters of risk and wear associated with this journey. Two important characteristics of the sea state are significant wave height and mean wave period. We propose a joint spatial model of these two quantities on the north Atlantic ocean. The model describes the distribution of the logarithm of the two quantities as a bivariate Gaussian random field, modeled as a solution to a system of coupled fractional stochastic partial differential equations. The bivariate random field is non-stationary and allows for arbitrary, and different, smoothness for the two marginal fields. The parameters of the model are estimated from data using a stepwise maximum likelihood method. The fitted model is used to derive the distribution of accumulated fatigue damage for a ship sailing a transatlantic route. Also, a method for estimating the risk of capsizing due to broaching-to based on the joint distribution of the two sea state characteristics is investigated. The risks are calculated for a transatlantic route between America and Europe using both data and the fitted model. The results show that the model compares well with observed data. It further shows that the bivariate model is needed and cannot simply be approximated by a model of significant wave height alone. © 2022 Elsevier Ltd
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| 2748. |
- Hildeman, Anders, 1984, et al.
(författare)
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Level set Cox processes
- 2018
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Ingår i: Spatial Statistics. - : Elsevier BV. - 2211-6753. ; 28, s. 169-193
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Tidskriftsartikel (refereegranskat)abstract
- An extension of the popular log-Gaussian Cox process (LGCP) model for spatial point patterns is proposed for data exhibiting fundamentally different behaviors in different subregions of the spatial domain. The aim of the analyst might be either to identify and classify these regions, to perform kriging, or to derive some properties of the parameters driving the random field in one or several of the subregions. The extension is based on replacing the latent Gaussian random field in the LGCP by a latent spatial mixture model specified using a categorically valued random field. This classification is defined through level set operations on a Gaussian random field and allows for standard stationary covariance structures, such as the Matern family, to be used to model random fields with some degree of general smoothness but also occasional and structured sharp discontinuities. A computationally efficient MCMC method is proposed for Bayesian inference and we show consistency of finite dimensional approximations of the model. Finally, the model is fitted to point pattern data derived from a tropical rainforest on Barro Colorado island, Panama. We show that the proposed model is able to capture behavior for which inference based on the standard LGCP is biased. (C) 2018 Elsevier B.V. All rights reserved.
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| 2749. |
- Hildner, Florian, et al.
(författare)
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Human adipose-derived stem cells contribute to chondrogenesis in coculture with human articular chondrocytes.
- 2009
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Ingår i: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-335X .- 1937-3341. ; 15:12, s. 3961-9
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Tidskriftsartikel (refereegranskat)abstract
- Adipose tissue is easily available and contains high numbers of stem cells that are capable for chondrogenic differentiation. We hypothesize that a partial substitution of chondrocytes with autologous adipose-derived stem cells (ASC) might be a possible strategy to reduce the number of chondrocytes needed in matrix-associated autologous chondrocyte transplantation. To lay the ground, in vitro coculture experiments were performed using human chondrocytes and human ASC. Chondrocytes were obtained from donors undergoing matrix-associated autologous chondrocyte transplantation. ASC were isolated from liposuction material. Chondrocytes and ASC were seeded either in fibrin (Tisseel; Baxter, Vienna, Austria) or collagen matrix (Tissue Fleece; Baxter, Unterschleissheim, Germany). RNA for quantitative reverse transcriptase (RT)-polymerase chain reaction was isolated after 2 weeks of culture in chondrogenic medium, and after 4 weeks samples were processed for histology. Related to the number of chondrocytes used, coculture with ASC led to strong increase in collagen type IX mRNA expression, which is an indicator for long-term stability of cartilage. Moderate upregulation was shown for SOX9, aggrecan, melanoma inhibitory activity, cartilage link protein 1, and cartilage oligomeric matrix protein mRNA. However, expression of collagen I and collagen II indicates the synthesis of fibrous tissue, which might be due to the use of dedifferentiated chondrocytes. Tisseel provided slightly better chondrogenic conditions than Tissue Fleece. These data support the possibility to take advantage of ASC in cartilage regeneration in conjunction with autologous chondrocytes.
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| 2750. |
- Hilgert, J., et al.
(författare)
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Segal–Bargmann and Weyl transforms on compact Lie groups. (With Joachim Hilgert)
- 2009
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Ingår i: Monatshefte für Mathematik. - : Springer Science and Business Media LLC. - 1436-5081 .- 0026-9255. ; 158:3, s. 285-305
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Tidskriftsartikel (refereegranskat)abstract
- We present an elementary derivation of the reproducing kernel for invariant Fock spaces associated with compact Lie groups which, as Ólafsson and Ørsted showed in (Lie Theory and its Applicaitons in Physics. World Scientific, 1996), yields a simple proof of the unitarity of Hall's Segal-Bargmann transform for compact Lie groups K. Further, we prove certain Hermite and character expansions for the heat and reproducing kernels on K and Kℂ. Finally, we introduce a Toeplitz (or Wick) calculus as an attempt to have a quantization of the functions on Kℂ as operators on the Hilbert space L2(K).
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