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Sökning: WFRF:(Turner Melanie)

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1.
  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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  • Dhanraj, Santhosh, et al. (författare)
  • Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN)
  • 2015
  • Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 52:11, s. 738-748
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Deadenylation regulates RNA function and fate. Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA. Little is known about the biological significance of germline mutations in PARN. Methods We identified mutations in PARN in patients with haematological and neurological manifestations. Genomic, biochemical and knockdown experiments in human marrow cells and in zebrafish have been performed to clarify the role of PARN in the human disease. Results We identified large monoallelic deletions in PARN in four patients with developmental delay or mental illness. One patient in particular had a severe neurological phenotype, central hypomyelination and bone marrow failure. This patient had an additional missense mutation on the non-deleted allele and severely reduced PARN protein and deadenylation activity. Cells from this patient had impaired oligoadenylation of specific H/ACA box small nucleolar RNAs. Importantly, PARN-deficient patient cells manifested short telomeres and an aberrant ribosome profile similar to those described in some variants of dyskeratosis congenita. Knocking down PARN in human marrow cells and zebrafish impaired haematopoiesis, providing further evidence for a causal link with the human disease. Conclusions Large monoallelic mutations of PARN can cause developmental/mental illness. Biallelic PARN mutations cause severe bone marrow failure and central hypomyelination.
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5.
  • Fathi, Kambiz, et al. (författare)
  • ALMA FOLLOWS STREAMING OF DENSE GAS DOWN TO 40 PC FROM THE SUPERMASSIVE BLACKHOLE IN NGC 1097
  • 2013
  • Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 770:2, s. L27-
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a kinematic analysis of the dense gas in the central 200 parsecs of thenearby galaxy NGC1097, based on Cycle 0 observations with the Atacama LargeMillimeter/sub-millimeter Array (ALMA). We use the HCN(4-3) line to trace the densest interstellar molecular gas (nH2 ~ 10^8 cm-3), and quantify its kinematics by means of Fourier decomposition. We find a striking similarity between the ALMA kinematic data and the analytic spiral in ow model that we have previously constructed based onionized gas velocity fields on larger scales. We are able to follow dense gas streamingdown to 40 pc distance from the supermassive black hole in this Seyfert 1 galaxy. In order to fulll marginal stability, we deduce that the dense gas is conned to a very thin disc, with 6.0+2.2-2.7 10^6 Msun dynamical mass inside a radius of 40 pc. Finally, we derive a dense gas in ow rate of 0.09Msun yr-1 at 40 pc radius. Combined with previous valuesfrom the H and CO gas, we calculate a combined molecular and ionized gas in ow rateof 0.2Msun yr-1 at 40 pc distance from the central supermassive black hole of NGC1097.
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  • Feitosa, Mary F., et al. (författare)
  • Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
  • 2018
  • Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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7.
  • Izumi, Takuma, et al. (författare)
  • ALMA OBSERVATIONS OF THE SUBMILLIMETER DENSE MOLECULAR GAS TRACERS IN THE LUMINOUS TYPE-1 ACTIVE NUCLEUS OF NGC 7469
  • 2015
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 811:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 1 observations of the central kiloparsec region of the luminous type. 1 Seyfert galaxy NGC 7469 with unprecedented high resolution (0.'' 5x0.'' 4 = 165 x 132 pc) at submillimeter wavelengths. Utilizing the wide. bandwidth of ALMA, we simultaneously obtained HCN(4-3), HCO+(4-3), CS(7-6), and partially CO(3-2) line maps, as well as the 860 mu m continuum. The region consists of the central similar to 1 '' component and the surrounding starburst ring with a radius of similar to 1.'' 5-2.'' 5. Several structures connect these components. Except for CO(3-2), these dense gas tracers are significantly concentrated toward the central similar to 1 '', suggesting their suitability to probe the nuclear regions of galaxies. Their spatial distribution resembles well those of centimeter and mid-infrared continuum emissions, but it is anticorrelated with the optical one, indicating the existence of dust-obscured star formation. The integrated intensity ratios of HCN(4-3)/HCO+(4-3) and HCN(4-3)/CS(7-6) are higher at the active galactic nucleus (AGN) position than at the starburst ring, which is consistent with our previous findings (submillimeter-HCN enhancement). However, the HCN(4-3)/HCO+(4-3) ratio at the AGN position of NGC 7469 (1.11 +/- 0.06) is almost half of the corresponding value of the low-luminosity type. 1 Seyfert galaxy NGC 1097 (2.0 +/- 0.2), despite the more than two orders of magnitude higher X-ray luminosity of NGC 7469. But the ratio is comparable to that of the close vicinity of the AGN of NGC 1068 (similar to 1.5). Based on these results, we speculate that some heating mechanisms other than X-ray (e.g., mechanical heating due to an AGN jet) can contribute significantly for shaping the chemical composition in NGC 1097.
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8.
  • Izumi, Takuma, et al. (författare)
  • Submillimeter ALMA Observations of the Dense Gas in the Low-Luminosity Type-1 Active Nucleus of NGC 1097
  • 2013
  • Ingår i: Publications of the Astronomical society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 65:5
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first 100 pc scale view of the dense molecular gas in the central similar to 1.3 kpc of the type-1 Seyfert NGC 1097, traced by HCN (J = 4-3) and HCO+ (J = 4-3) lines afforded with ALMA band 7. This galaxy shows significant HCN enhancement with respect to HCO+ and CO in the low-J transitions, which seems to be a common characteristic in AGN environments. Using the ALMA data, we consider the characteristics of the dense gas around this AGN, and search for the mechanism of HCN enhancement. We find a high HCN (J = 4-3) to HCO+ (J = 4-3) line ratio in the nucleus. The upper limit of the brightness temperature ratio of HCN (nu(2) = 1(1f), J = 4-3) to HCN (J = 4-3) is 0.08, which indicates that IR pumping does not significantly affect the pure rotational population in this nucleus. We also find a higher HCN (J = 4-3) to CS (J = 7-6) line ratio in NGC 1097 than in starburst galaxies, which is more than 12.7 on the brightness temperature scale. Combined with similar observations from other galaxies, we tentatively suggest that this ratio appears to be higher in AGN-host galaxies than in pure starburst ones, similar to the widely used HCN to HCO+ ratio. LTE and non-LTE modeling of the observed HCN and HCO+ lines using J = 4-3 and 1-0 data from ALMA, and J = 3-2 data from SMA, reveals a high HCN to HCO+ abundance ratio (5 <= [HCN]/[HCO+] <= 20: non-LTE analysis) in the nucleus, and that the high-J lines (J = 4-3 and 3-2) are emitted from dense (10(4.5) cm(-3) <= n(H2) <= 10(6) cm(-3)), hot (70 K <= T-kin <= 550 K) regions. Finally we propose that high-temperature chemistry is more plausible to explain the observed enhanced HCN emission in NGC 1097 than pure gas-phase PDR/XDR chemistry.
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9.
  • Izumi, Takuma, et al. (författare)
  • SUBMILLIMETER-HCN DIAGRAM FOR ENERGY DIAGNOSTICS IN THE CENTERS OF GALAXIES
  • 2016
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 818:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Compiling data from literature and the Atacama Large Millimeter/submillimeter Array archive, we show enhanced HCN(4-3)/HCO+(4-3) and/or HCN(4-3)/CS(7-6) integrated intensity ratios in circumnuclear molecular gas around active galactic nuclei (AGNs) compared to those in starburst (SB) galaxies (submillimeter HCN. enhancement). The number of sample galaxies is significantly increased from our previous work. We expect that this feature could potentially be an extinction-free energy diagnostic tool of nuclear regions of galaxies. Non-LTE radiative transfer modelings of the above molecular emission lines involving both collisional and radiative excitation, as well as a photon trapping effect, were conducted to investigate the cause of the high line ratios in AGNs. As a result, we found that enhanced abundance ratios of HCN to HCO+ and HCN to CS in AGNs as compared to SB galaxies by a factor of a few to even greater than or similar to 10 are a plausible explanation for the submillimeter HCN. enhancement. However, a counterargument of a systematically higher gas density in AGNs than in SB galaxies can also be a plausible scenario. Although we cannot fully distinguish. these two scenarios at this moment owing to an insufficient amount of multi-transition, multi-species data, the former scenario is indicative of abnormal chemical composition in AGNs. Regarding the actual mechanism to realize the composition, we suggest that it is difficult with conventional gas-phase X-ray-dominated region ionization models to reproduce the observed high line ratios. We might have to take into account other mechanisms such as neutral-neutral reactions that are efficiently activated in high-temperature environments and/or mechanically heated regions to further understand the high line ratios in AGNs.
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10.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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