| 1. |
- DeFronzo, Ralph A., et al.
(författare)
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Type 2 diabetes mellitus
- 2015
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Ingår i: Nature Reviews Disease Primers. - : Springer Science and Business Media LLC. - 2056-676X. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN.
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| 2. |
- Groome, Michelle J., et al.
(författare)
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Effectiveness of monovalent human rotavirus vaccine against admission to hospital for acute rotavirus diarrhoea in South African children : a case-control study
- 2014
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Ingår i: The Lancet - Infectious diseases. - : Elsevier. - 1473-3099 .- 1474-4457. ; 14:11, s. 1096-1104
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Tidskriftsartikel (refereegranskat)abstract
- Background The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme. Methods This case-control study was done at seven hospitals in South Africa between April 19,2010, and Oct 31,2012. The hospitals were located in a range of urban, pen-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14,2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 adjusted odds ratio x100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247. Findings Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40-68) for two doses and 40% (16-57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks-11 months (54%, 95% CI 32-68) and 12-23 months (61%, 35-77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34-80) and HIV-unexposed-uninfected children (54%, 31-69). Interpretation Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries.
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| 3. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 4. |
- Rosenfeld, Daniel, et al.
(författare)
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Global observations of aerosol-cloud-precipitation-climate interactions
- 2014
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Ingår i: Reviews of Geophysics. - 8755-1209. ; 52:4, s. 750-808
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Forskningsöversikt (refereegranskat)abstract
- Cloud drop condensation nuclei (CCN) and ice nuclei (IN) particles determine to a large extent cloud microstructure and, consequently, cloud albedo and the dynamic response of clouds to aerosol-induced changes to precipitation. This can modify the reflected solar radiation and the thermal radiation emitted to space. Measurements of tropospheric CCN and IN over large areas have not been possible and can be only roughly approximated from satellite-sensor-based estimates of optical properties of aerosols. Our lack of ability to measure both CCN and cloud updrafts precludes disentangling the effects of meteorology from those of aerosols and represents the largest component in our uncertainty in anthropogenic climate forcing. Ways to improve the retrieval accuracy include multiangle and multipolarimetric passive measurements of the optical signal and multispectral lidar polarimetric measurements. Indirect methods include proxies of trace gases, as retrieved by hyperspectral sensors. Perhaps the most promising emerging direction is retrieving the CCN properties by simultaneously retrieving convective cloud drop number concentrations and updraft speeds, which amounts to using clouds as natural CCN chambers. These satellite observations have to be constrained by in situ observations of aerosol-cloud-precipitation-climate (ACPC) interactions, which in turn constrain a hierarchy of model simulations of ACPC. Since the essence of a general circulation model is an accurate quantification of the energy and mass fluxes in all forms between the surface, atmosphere and outer space, a route to progress is proposed here in the form of a series of box flux closure experiments in the various climate regimes. A roadmap is provided for quantifying the ACPC interactions and thereby reducing the uncertainty in anthropogenic climate forcing.
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| 5. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 6. |
- Schwartz, Stephen E., et al.
(författare)
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Earth's Climate Sensitivity : Apparent Inconsistencies in Recent Assessments
- 2014
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Ingår i: Earths Future. - 2328-4277. ; 2:12, s. 601-605
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Tidskriftsartikel (refereegranskat)abstract
- Earth's equilibrium climate sensitivity (ECS) and forcing of Earth's climate system over the industrial era have been re-examined in two new assessments: the Fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change (IPCC), and a study by Otto et al. (2013). The ranges of these quantities given in these assessments and also in the Fourth (2007) IPCC Assessment are analyzed here within the framework of a planetary energy balance model, taking into account the observed increase in global mean surface temperature over the instrumental record together with best estimates of the rate of increase of planetary heat content. This analysis shows systematic differences among the several assessments and apparent inconsistencies within individual assessments. Importantly, the likely range of ECS to doubled CO2 given in AR5, 1.5-4.5 K/(3.7 W m(-2)) exceeds the range inferred from the assessed likely range of forcing, 1.2-2.9 K/(3.7 W m(-2)), where 3.7 W m(-2) denotes the forcing for doubled CO2. Such differences underscore the need to identify their causes and reduce the underlying uncertainties. Explanations might involve underestimated negative aerosol forcing, overestimated total forcing, overestimated climate sensitivity, poorly constrained ocean heating, limitations of the energy balance model, or a combination of effects.
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| 7. |
- Schwartz, Stephen E., et al.
(författare)
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Why Hasn't Earth Warmed as Much as Expected?
- 2010
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Ingår i: Journal of Climate. - 0894-8755 .- 1520-0442. ; 23:10, s. 2453-2464
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Tidskriftsartikel (refereegranskat)abstract
- The observed increase in global mean surface temperature (GMST) over the industrial era is less than 40% of that expected from observed increases in long-lived greenhouse gases together with the best-estimate equilibrium climate sensitivity given by the 2007 Assessment Report of the Intergovernmental Panel on Climate Change (IPCC). Possible reasons for this warming discrepancy are systematically examined here. The warming discrepancy is found to be due mainly to some combination of two factors: the IPCC best estimate of climate sensitivity being too high and/or the greenhouse gas forcing being partially offset by forcing by increased concentrations of atmospheric aerosols; the increase in global heat content due to thermal disequilibrium accounts for less than 25% of the discrepancy, and cooling by natural temperature variation can account for only about 15%. Current uncertainty in climate sensitivity is shown to preclude determining the amount of future fossil fuel CO2 emissions that would be compatible with any chosen maximum allowable increase in GMST; even the sign of such allowable future emissions is unconstrained. Resolving this situation, by empirical determination of the earth's climate sensitivity from the historical record over the industrial period or through use of climate models whose accuracy is evaluated by their performance over this period, is shown to require substantial reduction in the uncertainty of aerosol forcing over this period.
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| 8. |
- Stephens, Lucas, et al.
(författare)
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Archaeological assessment reveals Earth’s early transformation through land use
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 365:6456, s. 897-902
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Tidskriftsartikel (refereegranskat)abstract
- Humans began to leave lasting impacts on Earth’s surface starting 10,000 to 8000 years ago. Through a synthetic collaboration with archaeologists around the globe, Stephens et al. compiled a comprehensive picture of the trajectory of human land use worldwide during the Holocene (see the Perspective by Roberts). Hunter-gatherers, farmers, and pastoralists transformed the face of Earth earlier and to a greater extent than has been widely appreciated, a transformation that was essentially global by 3000 years before the present.Science, this issue p. 897; see also p. 865Environmentally transformative human use of land accelerated with the emergence of agriculture, but the extent, trajectory, and implications of these early changes are not well understood. An empirical global assessment of land use from 10,000 years before the present (yr B.P.) to 1850 CE reveals a planet largely transformed by hunter-gatherers, farmers, and pastoralists by 3000 years ago, considerably earlier than the dates in the land-use reconstructions commonly used by Earth scientists. Synthesis of knowledge contributed by more than 250 archaeologists highlighted gaps in archaeological expertise and data quality, which peaked for 2000 yr B.P. and in traditionally studied and wealthier regions. Archaeological reconstruction of global land-use history illuminates the deep roots of Earth’s transformation and challenges the emerging Anthropocene paradigm that large-scale anthropogenic global environmental change is mostly a recent phenomenon.
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| 9. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 10. |
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