| 51. |
- Backofen, Rolf, et al.
(författare)
-
Usage of bioinformatics tools and identification of information sources
- 2005
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Bioinformatics is an important application area for semantic web technologies as much of the data is online and accessible in XML format, as some sites already support web services, and as ontologies are widely used to annotate data. In this deliverable, we give a survey over 18 of the most important bioinformatics resources and discuss their availability and accessibility, which are two of the main criteria for these resources to act as bases for later demonstrators.
|
|
| 52. |
|
|
| 53. |
- Bastian, Patrick J., et al.
(författare)
-
Insignificant Prostate Cancer and Active Surveillance: From Definition to Clinical Implications
- 2009
-
Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 55:6, s. 1321-1332
-
Forskningsöversikt (refereegranskat)abstract
- Context: Due to early detection strategies, prostate cancer is diagnosed early in its natural history. It remains unclear whether all patients diagnosed with prostate cancer warrant radical treatment or may benefit from delayed intervention following active surveillance. Objective: A systematic review of active surveillance protocols to investigate the inclusion criteria for active surveillance and the outcome of treatment. Evidence acquisition: Medline was searched using the following terms: prostate cancer, active surveillance and expectant management for dates up to October 2008. Further studies were chosen on the basis of manual searches of reference lists and review papers. Evidence synthesis: Numerous studies on active surveillance were identified. The recent inclusion criteria of the studies are rather similar. Keeping the short follow-up of all studies in mind, the majority of men stay on active surveillance, and the percentage of patients receiving active treatment is as high as 35% of all patients. Once a patients requires active treatment, most patients still present with curable prostate cancer. Furthermore, only few deaths due to prostate cancer have occurred. Conclusions: Active surveillance is an alternative option to immediate treatment of men with presumed insignificant prostate cancer. It seems that criteria used to identify men with low-risk prostate cancer are rather similar, and immediate treatment of men meeting these criteria may result in an unnecessary number of treatments in these highly selected patients. Data from randomised trials comparing active surveillance and active treatment will provide additional insight into outcome and follow-up strategies. (C) 2009 Published by Elsevier B.V. on behalf of European Association of Urology.
|
|
| 54. |
- Bowman, Louise, et al.
(författare)
-
Understanding the use of observational and randomized data in cardiovascular medicine
- 2020
-
Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 41:27, s. 2571-2578
-
Tidskriftsartikel (refereegranskat)abstract
- The availability of large datasets from multiple sources [e.g. registries, biobanks, electronic health records (EHRs), claims or billing databases, implantable devices, wearable sensors, and mobile apps], coupled with advances in computing and analytic technologies, have provided new opportunities for conducting innovative health research. Equally, improved digital access to health information has facilitated the conduct of efficient randomized controlled trials (RCTs) upon which clinical management decisions can be based, for instance, by permitting the identification of eligible patients for recruitment and/or linkage for follow-up via their EHRs. Given these advances in cardiovascular data science and the complexities they behold, it is important that health professionals have clarity on the appropriate use and interpretation of observational, so-called 'real-world', and randomized data in cardiovascular medicine. The Cardiovascular Roundtable of the European Society of Cardiology (ESC) held a workshop to explore the future of RCTs and the current and emerging opportunities for gathering and exploiting complex observational datasets in cardiovascular research. The aim of this article is to provide a perspective on the appropriate use of randomized and observational data and to outline the ESC plans for supporting the collection and availability of clinical data to monitor and improve the quality of care of patients with cardiovascular disease in Europe and provide an infrastructure for undertaking pragmatic RCTs. Moreover, the ESC continues to campaign for greater engagement amongst regulators, industry, patients, and health professionals in the development and application of a more efficient regulatory framework that is able to take maximal advantage of new opportunities for improving the design and efficiency of observational studies and RCT in patients with cardiovascular disease.
|
|
| 55. |
- Claussnitzer, Melina, et al.
(författare)
-
Leveraging cross-species transcription factor binding site patterns: from diabetes risk Loci to disease mechanisms.
- 2014
-
Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 156:1-2, s. 343-358
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative computational analysis of phylogenetic conservation with a complexity assessment of co-occurring transcription factor binding sites (TFBS) can identify cis-regulatory variants and elucidate their mechanistic role in disease. Analysis of established type 2 diabetes risk loci revealed a striking clustering of distinct homeobox TFBS. We identified the PRRX1 homeobox factor as a repressor of PPARG2 expression in adipose cells and demonstrate its adverse effect on lipid metabolism and systemic insulin sensitivity, dependent on the rs4684847 risk allele that triggers PRRX1 binding. Thus, cross-species conservation analysis at the level of co-occurring TFBS provides a valuable contribution to the translation of genetic association signals to disease-related molecular mechanisms.
|
|
| 56. |
|
|
| 57. |
- de Villemereuil, Pierre, et al.
(författare)
-
Fluctuating optimum and temporally variable selection on breeding date in birds and mammals
- 2020
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 117:50, s. 31969-31978
-
Tidskriftsartikel (refereegranskat)abstract
- Temporal variation in natural selection is predicted to strongly impact the evolution and demography of natural populations, with consequences for the rate of adaptation, evolution of plasticity, and extinction risk. Most of the theory underlying these predictions assumes a moving optimum phenotype, with predictions expressed in terms of the temporal variance and auto-correlation of this optimum. However, empirical studies seldom estimate patterns of fluctuations of an optimum phenotype, precluding further progress in connecting theory with observations. To bridge this gap, we assess the evidence for temporal variation in selection on breeding date by modeling a fitness function with a fluctuating optimum, across 39 populations of 21 wild animals, one of the largest compilations of long-term datasets with individual measurements of trait and fitness components. We find compelling evidence for fluctuations in the fitness function, causing temporal variation in the magnitude, but not the direction of selection. However, fluctuations of the optimum phenotype need not directly translate into variation in selection gradients, because their impact can be buffered by partial tracking of the optimum by the mean phenotype. Analyzing individuals that reproduce in consecutive years, we find that plastic changes track movements of the optimum phenotype across years, especially in bird species, reducing temporal variation in directional selection. This suggests that phenological plasticity has evolved to cope with fluctuations in the optimum, despite their currently modest contribution to variation in selection.
|
|
| 58. |
- Doms, Andreas, et al.
(författare)
-
Ontologies and Text Mining as a Basis for a Semantic Web for the Life Sciences
- 2006
-
Ingår i: Reasoning Web, Second International Summer School. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783540384090 ; , s. 164-183
-
Bokkapitel (refereegranskat)abstract
- This book presents thoroughly arranged tutorial papers corresponding to lectures given by leading researchers at the Second International Summer School on Reasoning Web in Lisbon, Portugal, in September 2006. Building on the predessor school held in 2005 and published as LNCS 3564, the ten tutorial lectures presented provide competent coverage of current topics in semantic Web research and development.
|
|
| 59. |
- Fenstermacher, M.E., et al.
(författare)
-
DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
-
Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
|
|
| 60. |
- Gopalakrishnan, Shyam, et al.
(författare)
-
The population genomic legacy of the second plague pandemic
- 2022
-
Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 32:21, s. 4743-4751.e6
-
Tidskriftsartikel (refereegranskat)abstract
- Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%–40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th–19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.
|
|
