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- Mosley, Jonathan D., et al.
(författare)
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Probing the Virtual Proteome to Identify Novel Disease Biomarkers
- 2018
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Ingår i: Circulation. - 1524-4539. ; 138:22, s. 2469-2481
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Proteomic approaches allow measurement of thousands of proteins in a single specimen, which can accelerate biomarker discovery. However, applying these technologies to massive biobanks is not currently feasible because of the practical barriers and costs of implementing such assays at scale. To overcome these challenges, we used a "virtual proteomic" approach, linking genetically predicted protein levels to clinical diagnoses in >40 000 individuals. METHODS: We used genome-wide association data from the Framingham Heart Study (n=759) to construct genetic predictors for 1129 plasma protein levels. We validated the genetic predictors for 268 proteins and used them to compute predicted protein levels in 41 288 genotyped individuals in the Electronic Medical Records and Genomics (eMERGE) cohort. We tested associations for each predicted protein with 1128 clinical phenotypes. Lead associations were validated with directly measured protein levels and either low-density lipoprotein cholesterol or subclinical atherosclerosis in the MDCS (Malmö Diet and Cancer Study; n=651). RESULTS: In the virtual proteomic analysis in eMERGE, 55 proteins were associated with 89 distinct diagnoses at a false discovery rate q<0.1. Among these, 13 associations involved lipid (n=7) or atherosclerosis (n=6) phenotypes. We tested each association for validation in MDCS using directly measured protein levels. At Bonferroni-adjusted significance thresholds, levels of apolipoprotein E isoforms were associated with hyperlipidemia, and circulating C-type lectin domain family 1 member B and platelet-derived growth factor receptor-β predicted subclinical atherosclerosis. Odds ratios for carotid atherosclerosis were 1.31 (95% CI, 1.08-1.58; P=0.006) per 1-SD increment in C-type lectin domain family 1 member B and 0.79 (0.66-0.94; P=0.008) per 1-SD increment in platelet-derived growth factor receptor-β. CONCLUSIONS: We demonstrate a biomarker discovery paradigm to identify candidate biomarkers of cardiovascular and other diseases.
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- Rosa, Isabel M. D., et al.
(författare)
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Multiscale scenarios for nature futures
- 2017
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Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 1:10, s. 1416-1419
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Targets for human development are increasingly connected with targets for nature, however, existing scenarios do not explicitly address this relationship. Here, we outline a strategy to generate scenarios centred on our relationship with nature to inform decision-making at multiple scales.
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- Boyages, John, et al.
(författare)
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Liposuction for Advanced Lymphedema: A Multidisciplinary Approach for Complete Reduction of Arm and Leg Swelling
- 2015
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1534-4681 .- 1068-9265. ; 22, s. 1263-1270
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. This research describes and evaluates a liposuction surgery and multidisciplinary rehabilitation approach for advanced lymphedema of the upper and lower extremties. Methods. A prospective clinical study was conducted at an Advanced Lymphedema Assessment Clinic (ALAC) comprised of specialists in plastic surgery, rehabilitation, imaging, oncology, and allied health, at Macquarie University, Australia. Between May 2012 and 31 May 2014, a total of 104 patients attended the ALAC. Eligibility criteria for liposuction included (i) unilateral, non-pitting, International Society of Lymphology stage II/III lymphedema; (ii) limb volume difference greater than 25 %; and (iii) previously ineffective conservative therapies. Of 55 eligible patients, 21 underwent liposuction (15 arm, 6 leg) and had at least 3 months postsurgical follow-up (85.7 % cancer-related lymphedema). Liposuction was performed under general anesthesia using a published technique, and compression garments were applied intraoperatively and advised to be worn continuously thereafter. Limb volume differences, bioimpedance spectroscopy (L-Dex), and symptom and functional measurements (using the Patient-Specific Functional Scale) were taken presurgery and 4 weeks postsurgery, and then at 3, 6, 9, and 12 months postsurgery. Results. Mean presurgical limb volume difference was 45.1 % (arm 44.2 %; leg 47.3 %). This difference reduced to 3.8 % (arm 3.6 %; leg 4.3 %) by 6 months postsurgery, a mean percentage volume reduction of 89.6 % (arm 90.2 %; leg 88.2 %) [p < 0.001]. All patients had improved symptoms and function. Bioimpedance spectroscopy showed reduced but ongoing extracellular fluid, consistent with the underlying lymphatic pathology. Conclusions. Liposuction is a safe and effective option for carefully selected patients with advanced lymphedema. Assessment, treatment, and follow-up by a multidisciplinary team is essential.
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- Egerstedt, Anna, et al.
(författare)
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Profiling of the plasma proteome across different stages of human heart failure
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5830-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a major public health problem characterized by inability of the heart to maintain sufficient output of blood. The systematic characterization of circulating proteins across different stages of HF may provide pathophysiological insights and identify therapeutic targets. Here we report application of aptamer-based proteomics to identify proteins associated with prospective HF incidence in a population-based cohort, implicating modulation of immunological, complement, coagulation, natriuretic and matrix remodeling pathways up to two decades prior to overt disease onset. We observe further divergence of these proteins from the general population in advanced HF, and regression after heart transplantation. By leveraging coronary sinus samples and transcriptomic tools, we describe likely cardiac and specific cellular origins for several of the proteins, including Nt-proBNP, thrombospondin-2, interleukin-18 receptor, gelsolin, and activated C5. Our findings provide a broad perspective on both cardiac and systemic factors associated with HF development.
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- Interdonato, Giovanni, 1986-
(författare)
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Signal Processing Aspects of Cell-Free Massive MIMO
- 2018
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The fifth generation of mobile communication systems (5G) promises unprecedented levels of connectivity and quality of service (QoS) to satisfy the incessant growth in the number of mobile smart devices and the huge increase in data demand. One of the primary ways 5G network technology will be accomplished is through network densification, namely increasing the number of antennas per site and deploying smaller and smaller cells.Massive MIMO, where MIMO stands for multiple-input multiple-output, is widely expected to be a key enabler of 5G. This technology leverages an aggressive spatial multiplexing, from using a large number of transmitting/receiving antennas, to multiply the capacity of a wireless channel. A massive MIMO base station (BS) is equipped with a large number of antennas, much larger than the number of active users. The users are coherently served by all the antennas, in the same time-frequency resources but separated in the spatial domain by receiving very directive signals. By supporting such a highly spatially-focused transmission (precoding), massive MIMO provides higher spectral and energy efficiency, and reduces the inter-cell interference compared to existing mobile systems. The inter-cell interference is however becoming the major bottleneck as we densify the networks. It cannot be removed as long as we rely on a network-centric implementation, since the inter-cell interference concept is inherent to the cellular paradigm.Cell-free massive MIMO refers to a massive MIMO system where the BS antennas, herein referred to as access points (APs), are geographically spread out. The APs are connected, through a fronthaul network, to a central processing unit (CPU) which is responsible for coordinating the coherent joint transmission. Such a distributed architecture provides additional macro-diversity, and the co-processing at multiple APs entirely suppresses the inter-cell interference. Each user is surrounded by serving APs and experiences no cell boundaries. This user-centric approach, combined with the system scalability that characterizes the massive MIMO design, constitutes a paradigm shift compared to the conventional centralized and distributed wireless communication systems. On the other hand, such a distributed system requires higher capacity of back/front-haul connections, and the signal co-processing increases the signaling overhead.In this thesis, we focus on some signal processing aspects of cell-free massive MIMO. More specifically, we firstly investigate if the downlink channel estimation, via downlink pilots, brings gains to cell-free massive MIMO or the statistical channel state information (CSI) knowledge at the users is enough to reliably perform data decoding, as in conventional co-located massive MIMO. Allocating downlink pilots is costly resource-wise, thus we also propose resource saving-oriented strategies for downlink pilot assignment. Secondly, we study further fully distributed and scalable precoding schemes in order to outperform cell-free massive MIMO in its canonical form, which consists in single-antenna APs implementing conjugate beamforming (also known as maximum ratio transmission).
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