| 1. |
- Burstein, R., et al.
(author)
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Mapping 123 million neonatal, infant and child deaths between 2000 and 2017
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7778, s. 353-358
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Journal article (peer-reviewed)abstract
- Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations. © 2019, The Author(s).
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| 2. |
- Fitzmauric, C., et al.
(author)
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Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017 : A Systematic Analysis for the Global Burden of Disease Study
- 2019
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In: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 5:12, s. 1749-1768
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Journal article (peer-reviewed)abstract
- Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs).Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
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| 3. |
- Klingstrom, J., et al.
(author)
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Innate and adaptive immune responses against human Puumala virus infection : immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus-associated syndromes
- 2019
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In: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 285:5, s. 510-523
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Journal article (peer-reviewed)abstract
- Two related hyperinflammatory syndromes are distinguished following infection of humans with hantaviruses: haemorrhagic fever with renal syndrome (HFRS) seen in Eurasia and hantavirus pulmonary syndrome (HPS) seen in the Americas. Fatality rates are high, up to 10% for HFRS and around 35%-40% for HPS. Puumala virus (PUUV) is the most common HFRS-causing hantavirus in Europe. Here, we describe recent insights into the generation of innate and adaptive cell-mediated immune responses following clinical infection with PUUV. First described are studies demonstrating a marked redistribution of peripheral blood mononuclear phagocytes (MNP) to the airways, a process that may underlie local immune activation at the site of primary infection. We then describe observations of an excessive natural killer (NK) cell activation and the persistence of highly elevated numbers of NK cells in peripheral blood following PUUV infection. A similar vigorous CD8 Tcell response is also described, though Tcell responses decline with viraemia. Like MNPs, many NK cells and CD8 T cells also localize to the lung upon acute PUUV infection. Following this, findings demonstrating the ability of hantaviruses, including PUUV, to cause apoptosis resistance in infected target cells, are described. These observations, and associated inflammatory cytokine responses, may provide new insights into HFRS and HPS disease pathogenesis. Based on similarities between inflammatory responses in severe hantavirus infections and other hyperinflammatory disease syndromes, we speculate whether some therapeutic interventions that have been successful in the latter conditions may also be applicable in severe hantavirus infections.
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| 4. |
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| 5. |
- Bjorck, HM, et al.
(author)
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Altered DNA methylation indicates an oscillatory flow mediated epithelial-to-mesenchymal transition signature in ascending aorta of patients with bicuspid aortic valve
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 2777-
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Journal article (peer-reviewed)abstract
- Disturbed flow has been suggested to contribute to aneurysm susceptibility in bicuspid aortic valve (BAV) patients. Lately, flow has emerged as an important modulator of DNA methylation. Hear we combined global methylation analysis with in vitro studies of flow-sensitive methylation to identify biological processes associated with BAV-aortopathy and the potential contribution of flow. Biopsies from non-dilated and dilated ascending aortas were collected from BAV (n = 21) and tricuspid aortic valve (TAV) patients (n = 23). DNA methylation and gene expression was measured in aortic intima-media tissue samples, and in EA.hy926 and primary aortic endothelial cells (ECs) isolated from BAV and TAV exposed to oscillatory (±12 dynes/cm2) or laminar (12 dynes/cm2) flow. We show methylation changes related to epithelial-mesenchymal-transition (EMT) in the non-dilated BAV aorta, associated with oscillatory flow related to endocytosis. The results indicate that the flow-response in BAV ECs involves hypomethylation and increased expression of WNT/β-catenin genes, as opposed to an angiogenic profile in TAV ECs. The EMT-signature was exasperated in dilated BAV aortas. Aberrant EMT in BAV aortic walls could contribute to increased aneurysm susceptibility, and may be due to disturbed flow-exposure. Perturbations during the spatiotemporally related embryonic development of ascending aorta and semilunar valves can however not be excluded.
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| 6. |
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| 7. |
- Fakih, M., et al.
(author)
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SAFEPOWER project : Architecture for safe and power-efficient mixed-criticality systems
- 2017
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In: Microprocessors and microsystems. - : Elsevier. - 0141-9331 .- 1872-9436. ; 52, s. 89-105
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Journal article (peer-reviewed)abstract
- With the ever increasing industrial demand for bigger, faster and more efficient systems, a growing number of cores is integrated on a single chip. Additionally, their performance is further maximized by simultaneously executing as many processes as possible without regarding their criticality. Even safety critical domains like railway and avionics apply these paradigms under strict certification regulations. As the number of cores is continuously expanding, the importance of cost-effectiveness grows. One way to increase the cost-efficiency of such System on Chip (SoC) is to enhance the way the SoC handles its power resources. By increasing the power efficiency, the reliability of the SoC is raised because the lifetime of the battery lengthens. Secondly, by having less energy consumed, the emitted heat is reduced in the SoC which translates into fewer cooling devices. Though energy efficiency has been thoroughly researched, there is no application of those power saving methods in safety critical domains yet. The EU project SAFEPOWER1.
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| 8. |
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| 9. |
- Lagunas, E., et al.
(author)
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Resource Allocation for Cognitive Satellite Communications With Incumbent Terrestrial Networks
- 2015
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In: IEEE Transactions on Cognitive Communications and Networking. - : Institute of Electrical and Electronics Engineers (IEEE). - 2332-7731. ; 1:3, s. 305-317
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Journal article (peer-reviewed)abstract
- The lack of available unlicensed spectrum together with the increasing spectrum demand by multimedia applications has resulted in a spectrum scarcity problem, which affects satellite communications (SatCom) as well as terrestrial systems. The goal of this paper is to propose resource allocation (RA) techniques, i.e., carrier, power, and bandwidth allocation, for a cognitive spectrum utilization scenario where the satellite system aims at exploiting the spectrum allocated to terrestrial networks as the incumbent users without imposing harmful interference to them. In particular, we focus on the microwave frequency bands 17.7-19.7 GHz for the cognitive satellite downlink and 27.5-29.5 GHz for the cognitive satellite uplink, although the proposed techniques can be easily extended to other bands. In the first case, assuming that the satellite terminals are equipped with multiple low block noise converters (LNB), we propose a joint beamforming and carrier allocation scheme to enable cognitive space-to-Earth communications in the shared spectrum where fixed service (FS) microwave links have priority of operation. In the second case, however, the cognitive satellite uplink should not cause harmful interference to the incumbent FS system. For the latter, we propose a joint power and carrier allocation (JPCA) strategy followed by a bandwidth allocation scheme, which guarantees protection of the terrestrial FS system while maximizing the satellite total throughput. The proposed cognitive satellite exploitation techniques are validated with numerical simulations considering realistic system parameters. It is shown that the proposed cognitive exploitation framework represents a promising approach for enhancing the throughput of conventional satellite systems.
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| 10. |
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| 11. |
- Maleki, S, et al.
(author)
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Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves
- 2016
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 35712-
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Journal article (peer-reviewed)abstract
- Individuals with a bicuspid aortic valve (BAV) are at significantly higher risk of developing aortic complications than individuals with tricuspid aortic valves (TAV) and defective signaling during the embryonic development and/or life time exposure to abnormal hemodynamic have been proposed as underlying factors. However, an explanation for the molecular mechanisms of aortopathy in BAV has not yet been provided. We combined proteomics, RNA analyses, immunohistochemistry, and electron microscopy to identify molecular differences in samples of non-dilated ascending aortas from BAV (N = 62) and TAV (N = 54) patients. Proteomic analysis was also performed for dilated aortas (N = 6 BAV and N = 5 TAV) to gain further insight into the aortopathy of BAV. Our results collectively showed the molecular signature of an endothelial/epithelial-mesenchymal (EndMT/EMT) transition-like process, associated with instability of intimal cell junctions and activation of RHOA pathway in the intima and media layers of ascending aorta in BAV patients. We propose that an improper regulation of EndMT/EMT during the spatiotemporally related embryogenesis of semilunar valves and ascending aorta in BAV individuals may result in aortic immaturity and instability prior to dilation. Exasperation of EndMT/EMT state in post embryonic life and/or exposure to non-physiological hemodynamic could lead to the aneurysm of ascending aorta in BAV individuals.
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| 12. |
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| 13. |
- Politis, C., et al.
(author)
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Simultaneous Sensing and Transmission for Cognitive Radios With Imperfect Signal Cancellation
- 2017
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In: IEEE Transactions on Wireless Communications. - : Institute of Electrical and Electronics Engineers (IEEE). - 1536-1276 .- 1558-2248. ; 16:9, s. 5599-5615
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Journal article (peer-reviewed)abstract
- In conventional cognitive radio systems, the secondary user employs a “listen-before-talk” paradigm, where it senses if the primary user is active or idle, before it decides to access the licensed spectrum. However, this method faces challenges, with the most important one being the reduction of the secondary user's throughput, as no data transmission takes place during the sensing period. In this context, the idea of simultaneous spectrum sensing and data transmission is proposed. This paper studies a system model where this concept is obtained through the collaboration of the secondary transmitter with the secondary receiver. First, the secondary receiver decodes the signal from the secondary transmitter, removes it from the total received signal, and then carries out spectrum sensing in the remaining signal in order to determine the presence/absence of the primary user. Different from the existing literature, this paper considers the imperfect signal cancellation, evaluating how the decoding errors affect the sensing reliability, and derives the analytical expressions for the probability of false alarm. Finally, numerical results are presented illustrating the accuracy of the proposed analysis.
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| 14. |
- Scholz, Saskia, et al.
(author)
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Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways
- 2017
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In: PLoS Pathogens. - : Public library science. - 1553-7366 .- 1553-7374. ; 13:6
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Journal article (peer-reviewed)abstract
- Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs), including monocytes and dendritic cells (DCs), orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis. Here, we studied 17 patients infected with Puumala virus that causes a mild form of hemorrhagic fever with renal syndrome (HFRS). Bronchial biopsies as well as longitudinal blood draws were obtained from the patients. During the acute stage of disease, a significant influx of MNPs expressing HLA-DR, CD11c or CD123 was detected in the patients' bronchial tissue. In parallel, absolute numbers of MNPs were dramatically reduced in peripheral blood, coinciding with viremia. Expression of CCR7 on the remaining MNPs in blood suggested migration to peripheral and/or lymphoid tissues. Numbers of MNPs in blood subsequently normalized during the convalescent phase of the disease when viral RNA was no longer detectable in plasma. Finally, we exposed blood MNPs in vitro to Puumala virus, and demonstrated an induction of CCR7 expression on MNPs. In conclusion, the present study shows a marked redistribution of blood MNPs to the airways during acute hantavirus disease, a process that may underlie the local immune activation and contribute to immunopathogenesis in hantavirus-infected patients.
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| 15. |
- Sola-Riera, Caries, et al.
(author)
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Hantavirus Inhibits TRAIL-Mediated Killing of Infected Cells by Downregulating Death Receptor 5
- 2019
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In: Cell Reports. - : Cell Press. - 2211-1247. ; 28:8, s. 2124-2139
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Journal article (peer-reviewed)abstract
- Cytotoxic lymphocytes normally kill virus-infected cells by apoptosis induction. Cytotoxic granule-dependent apoptosis induction engages the intrinsic apoptosis pathway, whereas death receptor (DR)-dependent apoptosis triggers the extrinsic apoptosis pathway. Hantaviruses, single-stranded RNA viruses of the order Bunyavirales, induce strong cytotoxic lymphocyte responses in infected humans. Cytotoxic lymphocytes, however, are largely incapable of eradicating hantavirus-infected cells. Here, we show that the prototypic hantavirus, Hantaan virus (HTNV), induces TRAIL production but strongly inhibits TRAIL-mediated extrinsic apoptosis induction in infected cells by downregulating DR5 cell surface expression. Mechanistic analyses revealed that HTNV triggers both 26S proteasome-dependent degradation of DR5 through direct ubiquitination of DR5 and hampers DR5 transport to the cell surface. These results corroborate earlier findings, demonstrating that hantavirus also inhibits cytotoxic cell granule-dependent apoptosis induction. Together, these findings show that HTNV counteracts intrinsic and extrinsic apoptosis induction pathways, providing a defense mechanism utilized by hantaviruses to inhibit cytotoxic cell-mediated eradication of infected cells.
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