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THE INNOVATION A great contributor to primary care physician (PCP) burnout is the inability to 'unplug' from the electronic health record (EHR) for fear that urgent patient messages may be [...]

The Mt Samalas eruption, thought to have occurred in summer 1257, ranks as one of the most explosive sulfur-rich eruptions of the Common Era. Despite recent convergence, several dates have been proposed for the eruption ranging between 1256–1258, with, as of yet, no single combination of evidence that has been able to robustly distinguish between and exclude the other dates proposed for the Mt Samalas eruption. Widespread surface cooling and hydroclimate perturbations following the eruption have been invoked as contributing to a host of 13th century social and economic crises, although regional-scale variability in the post-eruption climate response remains uncertain. In this study we run ensemble simulations using the UK Earth System Model (UKESM1) with a range of eruption scenarios and initial conditions in order to compare our simulations with the most complete globally resolved multi-proxy database for the Mt Samalas eruption to date, incorporating tree rings, ice cores, and historical records. This allows more precise constraints to be placed on the year and season of the Mt Samalas eruption, as well as an investigation into the regionally heterogeneous post-eruption climate response. Using a multi-proxy to model comparison, we are able to robustly distinguish between July 1257 and January 1258 eruption scenarios, where the July 1257 ensemble simulation achieves considerably better agreement with spatially averaged and regionally resolved proxy surface temperature reconstructions. These reconstructions suggest the onset of significant cooling across Asia and Europe in 1258 and thus support the plausibility of previously inferred historical connections. Model-simulated temperature anomalies also point to severe surface cooling across the Southern Hemisphere with as of yet unexplored historical implications for impacted civilisations. Model simulations of polar sulfate deposition also reveal distinct differences in the timing of ice sheet deposition between the two simulated eruption dates, although comparison of the magnitude or asymmetric deposition of sulfate aerosol remains limited by large inter-model differences and complex intra-model dependencies. Overall, the multi-proxy to model comparison employed in this study has strong potential in constraining similar uncertainties in eruption source parameters for other historical eruptions for which sufficient coincident proxy records are available, although care is needed to avoid the pitfalls of model–multi-proxy comparison. [ABSTRACT FROM AUTHOR]

Abstract Background Global developmental delay and mental retardation are associated with X-linked disorders including Hunter syndrome (mucopolysaccharidosis type II) and Fragile X syndrome (FXS). Single nucleotide mutations in the iduronate 2-sulfatase (IDS) gene at Xq28 most commonly cause Hunter syndrome while a CGG expansion in the FMR1 gene at Xq27.3 is associated with Fragile X syndrome. Gene deletions of the Xq27-28 region are less frequently found in either condition with rare reports in females. Additionally, an association between Xq27-28 deletions and skewed X-inactivation of the normal X chromosome observed in previous studies suggested a primary role of the Xq27-28 region in X-inactivation. Case presentation We describe the clinical, molecular and biochemical evaluations of a four year-old female patient with global developmental delay and a hemizygous deletion of Xq27.3q28 (144,270,614-154,845,961 bp), a 10.6 Mb region that contains >100 genes including IDS and FMR1. A literature review revealed rare cases with similar deletions that included IDS and FMR1 in females with developmental delay, variable features of Hunter syndrome, and skewed X-inactivation of the normal X chromosome. In contrast, our patient exhibited skewed X-inactivation of the deleted X chromosome and tested negative for Hunter syndrome. Conclusions This is a report of a female with a 10.6 Mb Xq27-28 deletion with skewed inactivation of the deleted X chromosome. Contrary to previous reports, our observations do not support a primary role of the Xq27-28 region in X-inactivation. A review of the genes in the deletion region revealed several potential genes that may contribute to the patient’s developmental delays, and sequencing of the active X chromosome may provide insight into the etiology of this clinical presentation.

Open in new tab Download slide OBJECTIVES Thick-patch pulmonary homograft, autologous pericardium and CardioCel Neo are common patch materials for aortic arch reconstruction. Insufficient data exist on sutured patch strength and limits of use. We evaluated failure strength of these materials to develop a failure prediction model for clinical guidance. METHODS Patch failure strength was evaluated via sutured uniaxial and burst pressure testing. In sutured uniaxial testing, patches were sutured to aortic or Dacron tabs and pulled to failure. In burst pressure testing, patches were sewn into porcine aortas or Dacron grafts and pressurized to failure. Failure membrane tension was calculated. A prediction model of membrane tension versus vessel diameter was generated to guide clinical patch selection. RESULTS Combining sutured uniaxial and burst pressure test data, pulmonary homograft failure strength {0.61 [interquartile range (IQR): 0.44, 0.78] N/mm, n  = 21} was less than half that of autologous pericardium [2.22 (IQR: 1.65, 2.78) N/mm, n  = 15] and CardioCel Neo [1.31 (IQR: 1.20, 1.42) N/mm, n  = 20]. Pulmonary homograft burst pressure [245 (IQR: 202, 343) mmHg, n  = 7] was significantly lower than autologous pericardium [863 (IQR: 802, 919) mmHg, n  = 6] and CardioCel Neo [766 (IQR: 721, 833) mmHg, n  = 6]. Our model predicts failure limits for each patch material and outlines safety margins for combinations of aortic diameter and pressure. CONCLUSIONS Sutured failure strength of thick-patch pulmonary homograft was significantly lower than autologous pericardium and CardioCel Neo. Patient selection (predicted postoperative arch diameter and haemodynamics) and blood pressure management must be considered when choosing patch material for arch reconstruction. In older children and adolescents, autologous or bovine pericardium may be more suitable materials for aortic patch augmentation to minimize the risk of postoperative patch failure. [ABSTRACT FROM AUTHOR]

Volcanic eruptions that inject sulphur dioxide into the stratosphere have the potential to alter large-scale circulation patterns, such as the quasi-biennial oscillation (QBO), which can affect weather and transport of chemical species. Here, we conduct simulations of tropical volcanic eruptions using the UM-UKCA aerosol-climate model with an explicit representation of the QBO. Eruptions emitting 60 Tg of SO2 (i.e., 1815 Mt. Tambora-magnitude) and 15 Tg of SO2 (i.e., 1991 Mt. Pinatubo-magnitude) were simulated at the equator initiated during two different QBO states. We show that tropical eruptions delay the progression of the QBO phases, with the magnitude of the delay dependent on the initial wind shear in the lower stratosphere and a much longer delay when the shear is easterly than when it is westerly. The QBO response in our model is driven by vertical advection of momentum by the stronger tropical upwelling caused by heating due to the increased volcanic sulfate aerosol loading. Direct aerosol-induced warming with subsequent thermal wind adjustment, as proposed by previous studies, is found to only play a secondary role. This interpretation of the response is supported by comparison with a simple dynamical model. The dependence of the magnitude of the response on the initial QBO state results from differences in the QBO secondary circulation. In the easterly shear zone of the QBO, the vertical component of the secondary circulation is upward and reinforces the anomalous upwelling driven by volcanic aerosol heating, whereas in the westerly shear zone the vertical component is downward and opposes the aerosol-induced upwelling. We also find a change to the latitudinal structure of the QBO, with the westerly phase of the QBO strengthening in the hemisphere with the lowest sulfate aerosol burden. Overall, our study suggests that tropical eruptions of Pinatubo-magnitude or larger could force changes to the progression of the QBO, with particularly disruptive outcomes for the QBO if the eruption occurs during the easterly QBO shear. [ABSTRACT FROM AUTHOR]

Here we investigate how uncertainties in the solar and volcanic forcing records of the past millennium affect the large-scale temperature response of a 2-box impulse response model. We use different published solar forcing records and present a new volcanic forcing ensemble which accounts for random uncertainties in eruption dating and sulfur injection amount. The simulations are compared to proxy reconstructions from PAGES 2k and Northern hemispheric tree-ring data. We find that low solar forcing is most consistent with all the proxy reconstructions, even when accounting for volcanic uncertainty and that the residuals are well in line with CMIP6 control variability at centennial timescales. Volcanic forcing uncertainty induces a significant spread in the temperature response, especially at periods of peak forcing. For individual eruptions and superposed epoch analyses volcanic uncertainty can strongly affect the agreement with proxy reconstructions, and may explain previous proxy-model discrepancies. [ABSTRACT FROM AUTHOR]