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- Hillmer, AM, et al.
(författare)
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Comprehensive long-span paired-end-tag mapping reveals characteristic patterns of structural variations in epithelial cancer genomes
- 2011
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 21:5, s. 665-675
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Tidskriftsartikel (refereegranskat)abstract
- Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long-span paired-end-tag (PET) sequencing approach using 10-Kb genomic DNA inserts to study human genome structural variations (SVs). The use of a 10-Kb insert size allows the identification of breakpoints within repetitive or homology-containing regions of a few kilobases in size and results in a higher physical coverage compared with small insert libraries with the same sequencing effort. We have applied this approach to comprehensively characterize the SVs of 15 cancer and two noncancer genomes and used a filtering approach to strongly enrich for somatic SVs in the cancer genomes. Our analyses revealed that most inversions, deletions, and insertions are germ-line SVs, whereas tandem duplications, unpaired inversions, interchromosomal translocations, and complex rearrangements are over-represented among somatic rearrangements in cancer genomes. We demonstrate that the quantitative and connective nature of DNA–PET data is precise in delineating the genealogy of complex rearrangement events, we observe signatures that are compatible with breakage-fusion-bridge cycles, and we discover that large duplications are among the initial rearrangements that trigger genome instability for extensive amplification in epithelial cancers.
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- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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- Zhen, XM, et al.
(författare)
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Clinical and economic impact of methicillin-resistant Staphylococcus aureus: a multicentre study in China
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 3900-
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Tidskriftsartikel (refereegranskat)abstract
- Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious threat to global health. In China, the proportion of S. aureus isolates that were MRSA was 44.6% in 2014. The clinical and economic impact of MRSA in China remains largely uninvestigated. This study aims to compare the differences in hospital costs, length of hospital stay, and hospital mortality rate between MRSA and methicillin-susceptible S. aureus (MSSA) colonization or infection and between MRSA cases and those without an S. aureus infection. A retrospective and multicentre study was conducted in four tertiary hospitals in China between 2013 and 2015. Inpatient characteristics and hospital costs were collected from electronic medical records. We conducted propensity score matching (PSM) to eliminate selection bias by balancing the potential confounding variables between the two groups. The main indicators included hospital costs, length of hospital stay, and hospital mortality rate. A total of 1,335 inpatients with MRSA, 1,397 with MSSA, and 33,606 without an S. aureus infection were included. PSM obtained 954 and 1,313 pairs between the MRSA and MSSA groups and between the MRSA and S. aureus-free groups, respectively. After PSM, MRSA colonization or infection is associated with an increased total hospital cost ranging from $3,220 to $9,606, an excess length of hospital stay of 6 days–14 days, and an attributable hospital mortality rate of 0–3.58%. Between the MRSA and MSSA groups, MRSA colonization or infection was significantly associated with a higher total hospital cost and longer length of hospital stay among survivors but not among non-survivors; however, there were no differences in the hospital mortality rate between these two groups. Between the MRSA and the S. aureus-free groups, MRSA colonization or infection was significantly associated with an increased total hospital cost, a prolonged length of hospital stay and a higher hospital mortality rate among both survivors and non-survivors. It is critical to quantify the clinical and economic impact of MRSA to justify resource allocation for the development of strategies to improve clinical outcomes and to reduce the economic burden.
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