An Update on Statistical Boosting in Biomedicine.
Ontology highlight
ABSTRACT:
SUBMITTER: Mayr A
PROVIDER: S-EPMC5558647 | biostudies-other | 2017
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Genome-wide association studies (GWAS) have identified a large number of gene variants associated with schizophrenia, but these variants explain only a small portion of the heritability. It is becoming increasingly clear that schizophrenia is influenced by many genes, most of which have effects too small to be identified using traditional GWAS statistical methods. By applying recently developed Empirical Bayes statistical approaches, we have demonstrated that functional genic elements show differential contribution to phenotypic variance, with some elements (regulatory regions and exons) showing strong enrichment for association with schizophrenia. Applying related methods, we also showed abundant genetic overlap (pleiotropy) between schizophrenia and other phenotypes, including bipolar disorder, cardiovascular disease risk factors, and multiple sclerosis. We estimated the number of gene variants with effects in schizophrenia and bipolar disorder to be approximately 1.2%. By applying our novel statistical framework, we dramatically improved gene discovery and detected a large number of new gene loci associated with schizophrenia that have not yet been identified with standard GWAS methods. Utilizing independent schizophrenia substudies, we showed that these new loci have high replication rates in de novo samples, indicating that they likely represent true schizophrenia risk genes. The new statistical tools provide a powerful approach for uncovering more of the missing heritability of schizophrenia and other complex disorders. In conclusion, the highly polygenic architecture of schizophrenia strongly suggests the utility of research approaches that recognize schizophrenia neuropathology as a complex dynamic system, with many small gene effects integrated in functional networks.
| S-EPMC3885310 | biostudies-literature
Project description:The value of a statistical life (VSL) estimates individuals' willingness to trade wealth for mortality risk reduction. This economic parameter is often a major component of the quantified benefits estimated in the evaluation of government policies related to health and safety. This study reviewed the literature to update the VSL recommended for Australian policy appraisals. A systematic literature review was conducted to capture Australian primary studies and international review papers reporting VSL estimates published from 2007 to January 2019. International estimates were adjusted for income differences and the median VSL estimate was extracted from each review study. VSL estimates were used to calculate the value of a statistical life year. Of the 18 studies that met the inclusion criteria, two studies were primary Australian studies with a weighted mean VSL of A$7.0 million in 2017 values. The median VSL in the review studies was A$7.3 million. For Australian public policy appraisals, we recommend the consideration of a base case VSL for people of all ages and across all risk contexts of A$7.0 million. Sensitivity analyses could use a high value of A$7.3 million and a low value that reflects the value (A$4.3 million) currently recommended by the Australian government.
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Project description:BACKGROUND:Immune system abnormalities have been repeatedly observed in several psychiatric disorders, including severe depression and anxiety. However, whether specific immune mediators play an early role in the etiopathogenesis of these disorders remains unknown. METHODS:In a longitudinal design, component-wise gradient boosting was used to build models of depression, assessed by the Mood-Feelings Questionnaire-Child (MFQC), and anxiety, assessed by the Screen for Child Anxiety Related Emotional Disorders (SCARED) in 254 adolescents from a large set of candidate predictors, including sex, race, 39 inflammatory proteins, and the interactions between those proteins and time. Each model was reduced via backward elimination to maximize parsimony and generalizability. RESULTS:Component-wise gradient boosting and model reduction found that female sex, growth- regulated oncogene (GRO), and transforming growth factor alpha (TGF-alpha) predicted depression, while female sex predicted anxiety. LIMITATIONS:Differential onset of puberty as well as a lack of control for menstrual cycle may also have been responsible for differences between males and females in the present study. In addition, investigation of all possible nonlinear relationships between the predictors and the outcomes was beyond the computational capacity and scope of the present research. CONCLUSIONS:This study highlights the need for novel statistical modeling to identify reliable biological predictors of aberrant psychological behavior.
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Project description:BackgroundRecurrent bleeding from an intracranial aneurysm after subarachnoid hemorrhage (SAH) is associated with unfavorable outcome. Recurrent bleeding before aneurysm occlusion can be performed occurs in up to one in five patients and most often happens within the first 6 h after the primary hemorrhage. Reducing the rate of recurrent bleeding could be a major factor in improving clinical outcome after SAH. Tranexamic acid (TXA) reduces the risk of recurrent bleeding but has thus far not been shown to improve functional outcome, probably because of a higher risk of delayed cerebral ischemia (DCI). To reduce the risk of ultraearly recurrent bleeding, TXA should be administered as soon as possible after diagnosis and before transportation to a tertiary care center. If TXA is administered for a short duration (i.e., < 24 h), it may not increase the risk of DCI. The aim of this paper is to present in detail the statistical analysis plan (SAP) of the ULTRA trial (ULtra-early TRranexamic Acid after Subarachnoid Hemorrhage), which is currently enrolling patients and investigating whether ultraearly and short-term TXA treatment in patients with aneurysmal SAH improves clinical outcome at 6 months.Methods/designThe ULTRA trial is a multicenter, prospective, randomized, open, blinded endpoint, parallel-group trial currently ongoing at 8 tertiary care centers and 16 of their referral centers in the Netherlands. Participants are randomized to standard care or to receive TXA at a loading dose of 1 g, immediately followed by 1 g every 8 h for a maximum of 24 h, in addition to standard care, as soon as SAH is diagnosed. In the TXA group, TXA administration is stopped immediately prior to treatment (coil or clip) of the causative aneurysm. Primary outcome is the modified Rankin Scale (mRS) score at 6 months after SAH, dichotomized into good (mRS 0-3) and poor (mRS 4-6) outcomes, assessed blind to treatment allocation. Secondary outcomes include case fatalities at 30 days and at 6 months and causes of poor clinical outcome. Safety outcomes are recurrent bleeding, DCI, hydrocephalus, per-procedural complications, and other complications such as infections occurring during hospitalization. Data analyses will be according to this prespecified SAP.Trial registrationNetherlands Trial Register, NTR3272. Registered on 25 January 2012. ClinicalTrials.gov, NCT02684812. Registered on 17 February 2016.
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Project description:SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multicenter pragmatic mega-trial to examine the optimum treatment strategy for the first- and second-line treatments for unipolar major depressive episodes. The trial has three steps and two randomizations. Step I randomization compares the minimum and the maximum dosing strategy for the first-line antidepressant. Step II randomization compares the continuation, augmentation or switching strategy for the second-line antidepressant treatment. Step III is a naturalistic continuation phase. The original protocol was published in 2011, and we hereby report its updated protocol including the statistical analysis plan.We implemented two important changes to the original protocol. One is about the required sample size, reflecting the smaller number of dropouts than had been expected. Another is in the organization of the primary and secondary outcomes in order to make the report of the main trial results as pertinent and interpretable as possible for clinical practices. Due to the complexity of the trial, we plan to report the main results in two separate reports, and this updated protocol and the statistical analysis plan have laid out respective primary and secondary outcomes and their analyses. We will convene the blind interpretation committee before the randomization code is broken.This paper presents the updated protocol and the detailed statistical analysis plan for the SUN(^_^)D trial in order to avoid reporting bias and data-driven results.ClinicalTrials.gov: NCT01109693 (registered on 21 April 2010).
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Project description:First expansion of the public Tomato brown rugose fruit virus (ToBRFV) Nextstrain build inclusion of new genomic and epidemiological data
| PRJEB42296 | ENA
Project description:The objective of this assay was to determine the effect of ZIKV on host cellular pathways
2017-07-01 | GSE94494 | GEO
Project description:Thermoelectric efficiency is defined as the ratio of power delivered to the load of a device to the rate of heat flow from the source. Till date, it has been studied in presence of thermodynamic constraints set by the Onsager reciprocal relation and the second law of thermodynamics that severely bottleneck the thermoelectric efficiency. In this study, we propose a pathway to bypass these constraints using a time-dependent control and present a theoretical framework to study dynamic thermoelectric transport in the far from equilibrium regime. The presence of a control yields the sought after substantial efficiency enhancement and importantly a significant amount of power supplied by the control is utilised to convert the wasted-heat energy into useful-electric energy. Our findings are robust against nonlinear interactions and suggest that external time-dependent forcing, which can be incorporated with existing devices, provides a beneficial scheme to boost thermoelectric efficiency.
| S-EPMC4604463 | biostudies-other
Project description:http://www.nature.com/ng/journal/v33/n2/abs/ng1086.html. Little is known about broad patterns of variation and evolution of gene expression during any developmental process. Here we investigate variation in genome-wide gene expression among Drosophila simulans, Drosophila yakuba and four strains of Drosophila melanogaster during a major developmental transition?the start of metamorphosis. Differences in gene activity between these lineages follow a phylogenetic pattern, and 27% of all of the genes in these genomes differ in their developmental gene expression between at least two strains or species. We identify, on a gene-by-gene basis, the evolutionary forces that shape this variation and show that, both within the transcriptional network that controls metamorphosis and across the whole genome, the expression changes of transcription factor genes are relatively stable, whereas those of their downstream targets are more likely to have evolved. Our results demonstrate extensive evolution of developmental gene expression among closely related species. Extended from the original publication by updating annotation to release 4.0 and using 8 arrays for each strain/species. All Drosophila yakuba arrays are new. see also: PMID: 15122255. http://www.nature.com/ng/journal/v36/n6/abs/ng1355.html Gu Z, Rifkin SA, White KP, Li WH Duplicate genes increase gene expression diversity within and between species.
2010-06-10 | E-GEOD-2642 | biostudies-arrayexpress