| 221. |
- Ryan, Dermot, et al.
(författare)
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Use of electronic medical records and biomarkers to manage risk and resource efficiencies
- 2017
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Ingår i: EUROPEAN CLINICAL RESPIRATORY JOURNAL. - : TAYLOR & FRANCIS LTD. - 2001-8525. ; 4, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- The migration from paper to electronic medical records (EMRs) was motivated by the administrative need to record, retrieve and process increasing amounts of clinical data in the 1980s. In the intervening period, there has been growing recognition of the potential of such records for achieving care efficiencies, informing clinical decision making and real-life research. EMRs can be used to characterise patient groups, management approaches and differential outcomes. Characterisation can also help with identification of potential biomarkers for future risk determination and likely treatment response. The future heralds even greater opportunities through integration of clinical records and a range of technology-based solutions within a more complete electronic health record (EHR). Through application of algorithms based on identified risk predictors and disease determinants, clinical records could also be used to enable risk stratification of patients to optimise targeted interventions, conserving resources to achieve individual patient and system-wide benefit. In this review, we reflect on the evolution of the EMR and EHR and discuss current and emerging opportunities, particularly with respect to biomarkers and targeting of innovative biologic interventions. We also consider some of the critical issues associated with realising the potential of the EHR as a clinical aid and research tool in an age of emerging technologies.
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| 222. |
- Sailer, Anna, et al.
(författare)
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A genome-wide association study in multiple system atrophy
- 2016
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Ingår i: Neurology. - 0028-3878. ; 87:15, s. 1591-1598
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). Methods: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. Results: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10-6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. Conclusions: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps.
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| 223. |
- Sakabe, Noboru J, et al.
(författare)
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Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth.
- 2020
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:49
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Tidskriftsartikel (refereegranskat)abstract
- While a genetic component of preterm birth (PTB) has long been recognized and recently mapped by genome-wide association studies (GWASs), the molecular determinants underlying PTB remain elusive. This stems in part from an incomplete availability of functional genomic annotations in human cell types relevant to pregnancy and PTB. We generated transcriptome (RNA-seq), epigenome (ChIP-seq of H3K27ac, H3K4me1, and H3K4me3 histone modifications), open chromatin (ATAC-seq), and chromatin interaction (promoter capture Hi-C) annotations of cultured primary decidua-derived mesenchymal stromal/stem cells and in vitro differentiated decidual stromal cells and developed a computational framework to integrate these functional annotations with results from a GWAS of gestational duration in 56,384 women. Using these resources, we uncovered additional loci associated with gestational duration and target genes of associated loci. Our strategy illustrates how functional annotations in pregnancy-relevant cell types aid in the experimental follow-up of GWAS for PTB and, likely, other pregnancy-related conditions.
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| 224. |
- Santana, Felipe A., et al.
(författare)
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Final Targeting Strategy for the SDSS-IV APOGEE-2S Survey
- 2021
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 162:6
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Tidskriftsartikel (refereegranskat)abstract
- APOGEE is a high-resolution (R similar to 22,000), near-infrared, multi-epoch, spectroscopic survey of the Milky Way. The second generation of the APOGEE project, APOGEE-2, includes an expansion of the survey to the Southern Hemisphere called APOGEE-2S. This expansion enabled APOGEE to perform a fully panoramic mapping of all of the main regions of the Milky Way; in particular, by operating in the H band, APOGEE is uniquely able to probe the dust-hidden inner regions of the Milky Way that are best accessed from the Southern Hemisphere. In this paper we present the targeting strategy of APOGEE-2S, with special attention to documenting modifications to the original, previously published plan. The motivation for these changes is explained as well as an assessment of their effectiveness in achieving their intended scientific objective. In anticipation of this being the last paper detailing APOGEE targeting, we present an accounting of all such information complete through the end of the APOGEE-2S project; this includes several main survey programs dedicated to exploration of major stellar populations and regions of the Milky Way, as well as a full list of programs contributing to the APOGEE database through allocations of observing time by the Chilean National Time Allocation Committee and the Carnegie Institution for Science. This work was presented along with a companion article, Beaton et al. (2021), presenting the final target selection strategy adopted for APOGEE-2 in the Northern Hemisphere.
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| 225. |
- Sawalha, Amr H., et al.
(författare)
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Common variants within MECP2 confer risk of systemic lupus erythematosus
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:3, s. e1727-
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a predominantly female autoimmune disease that affects multiple organ systems. Herein, we report on an X-chromosome gene association with SLE. Methyl-CpG-binding protein 2 (MECP2) is located on chromosome Xq28 and encodes for a protein that plays a critical role in epigenetic transcriptional regulation of methylation-sensitive genes. Utilizing a candidate gene association approach, we genotyped 21 SNPs within and around MECP2 in SLE patients and controls. We identify and replicate association between SLE and the genomic element containing MECP2 in two independent SLE cohorts from two ethnically divergent populations. These findings are potentially related to the overexpression of methylation-sensitive genes in SLE.
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| 226. |
- Saxena, Richa, et al.
(författare)
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Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
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Tidskriftsartikel (refereegranskat)abstract
- New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
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| 227. |
- Schumacher, Fredrick R., et al.
(författare)
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Genome-wide association study identifies new prostate cancer susceptibility loci
- 2011
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Ingår i: Human Molecular Genetics. - London : IRL Press. - 0964-6906 .- 1460-2083. ; 20:19, s. 3867-3875
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade >= 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P = 4.3 x 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P = 8.6 x 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P = 0.72 and P = 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.
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| 228. |
- Segev, Gideon, et al.
(författare)
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The 2022 solar fuels roadmap
- 2022
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Ingår i: Journal of Physics D. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 55:32
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Tidskriftsartikel (refereegranskat)abstract
- Renewable fuel generation is essential for a low carbon footprint economy. Thus, over the last five decades, a significant effort has been dedicated towards increasing the performance of solar fuels generating devices. Specifically, the solar to hydrogen efficiency of photoelectrochemical cells has progressed steadily towards its fundamental limit, and the faradaic efficiency towards valuable products in CO2 reduction systems has increased dramatically. However, there are still numerous scientific and engineering challenges that must be overcame in order to turn solar fuels into a viable technology. At the electrode and device level, the conversion efficiency, stability and products selectivity must be increased significantly. Meanwhile, these performance metrics must be maintained when scaling up devices and systems while maintaining an acceptable cost and carbon footprint. This roadmap surveys different aspects of this endeavor: system benchmarking, device scaling, various approaches for photoelectrodes design, materials discovery, and catalysis. Each of the sections in the roadmap focuses on a single topic, discussing the state of the art, the key challenges and advancements required to meet them. The roadmap can be used as a guide for researchers and funding agencies highlighting the most pressing needs of the field.
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| 229. |
- Sharma, Hari Shanker, et al.
(författare)
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Chronic Treatment with Nanoparticles Exacerbate Hyperthermia Induced Blood-Brain Barrier Breakdown, Cognitive Dysfunction and Brain Pathology in the Rat : Neuroprotective Effects of Nanowired-Antioxidant Compound H-290/51
- 2009
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Ingår i: Journal of Nanoscience and Nanotechnology. - 1533-4880 .- 1533-4899. ; 9:8, s. 5073-5090
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Tidskriftsartikel (refereegranskat)abstract
- The possibility that chronic exposure of nanoparticles may alter stress reaction and brain pathology following hyperthermia was examined in a rat model. Engineered nanoparticles from Ag or M Cu (approximate to 50-60 nm) were administered (30 mg/kg, i.p.) once daily for 1 week in young male rats. M On the 8th day these animals were subjected to 4 h heat stress at 38 degrees C in a BOD incubator. In these animals stress symptoms, blood-brain barrier (BBB) permeability, cognitive and motor functions and brain pathology were examined. Subjection of nanoparticle treated rats to heat stress showed exacerbation of stress symptoms i.e., hyperthermia, salivation and prostration and exhibited greater BBB disruption, brain edema formation, impairment of cognitive and motor functions M and brain damage compared to normal animals. This enhanced brain pathology in heat stress was most marked in animals that received Ag nanoparticles compared to Cu treatment. Treatment with antioxidant compound H-290/51 either 30 min or 60 min after heat stress did not alter hyperthermia M induce brain pathology in nanoparticle treated rats. Whereas, administration of nanowired-H-290/51 after 30 min or 60 min heat stress markedly attenuated BBB disruption, sensory motor function and brain pathology. These results suggest that chronic nanoparticles treatment exacerbate hyperthermia induced brain pathology that is significantly attenuated by nanowired but not normal H-290/51 compound. Taken together, our observations suggest that nano-wired drug delivery of H-290/51 is a promising approach to induce neuroprotection in hyperthermia induced brain pathology, not reported earlier.
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| 230. |
- Sharma, Manu, et al.
(författare)
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Large-scale replication and heterogeneity in Parkinson disease genetic loci
- 2012
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Ingår i: Neurology. - 1526-632X. ; 79:7, s. 67-659
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown.METHODS: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry.RESULTS: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I(2) estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD.CONCLUSION: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.
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