Cystic fibrosis–related diabetes (CFRD) is a common comorbidity in cystic fibrosis with pancreatic insufficiency occurring early in the disease process. Current treatment is exogenous insulin therapy as CFRD is due to impaired insulin secretion. Recent small studies have shown improvement in endogenous insulin secretion with a short period of ivacaftor therapy in primarily pediatric patients with cystic fibrosis transmembrane conductance regulator mutations amenable to potentiation. In this article, we present the case of an adult patient with long-standing CFRD who developed sustained improvement in glycemic control after initiation of ivacaftor.
BackgroundTwo congenital bleeding diatheses have been identified in Thoroughbred horses: Glanzmann thrombasthenia (GT) and a second, novel diathesis associated with abnormal platelet function in response to collagen and thrombin stimulation.Hypothesis/ObjectivesPlatelet dysfunction in horses with this second thrombasthenia results from a secretory defect.AnimalsTwo affected and 6 clinically normal horses.MethodsEx vivo study. Washed platelets were examined for (1) expression of the αIIb‐β3 integrin; (2) fibrinogen binding capacity in response to ADP and thrombin; (3) secretion of dense and α‐granules; (4) activation of the mammalian target of rapamycin (mTOR)‐protein kinase B (AKT) signaling pathway; and (5) cellular distribution of phosphatidylinositol‐4‐phosphate‐3‐kinase, class 2B (PIK3C2B) and SH2 containing inositol‐5′‐phosphatase 1 (SHIP1).ResultsPlatelets from affected horses expressed normal amounts of αIIb‐β3 integrin and bound fibrinogen normally in response to ADP, but bound 80% less fibrinogen in response to thrombin. α‐granules only released 50% as much Factor V as control platelets, but dense granules released their contents normally. Protein kinase B (AKT) phosphorylation was reduced after thrombin activation, but mTOR Complex 2 (mTORC2) and phosphoinositide‐dependent kinase 1 (PDK1) signaling were normal. SH2‐containing inositol‐5'‐phosphatase 1 (SHIP1) did not localize to the cytoskeleton of affected platelets and was decreased overall consistent with reduced AKT phosphorylation.Conclusions and clinical significanceDefects in fibrinogen binding, granule secretion, and signal transduction are unique to this thrombasthenia, which we designate as atypical equine thrombasthenia.
The Bauer Field was discovered in August 2011 on the Western Flank of the Cooper-Eromanga Basin. Bauer 1 discovered an 11 m oil column in the Namur Sandstone, directly overlain by a 4 m oil column in the McKinlay Member. The Bauer Field has been developed by vertical wells targeting the high deliverability Namur Sandstone with the McKinlay Member as a secondary target. In 2017 the decision was made to specifically target the McKinlay Member with a horizontal well, requiring a multi-disciplinary approach to combine geological, geophysical and engineering datasets.
The McKinlay Member is 3–5 m in thickness and below seismic resolution with the wavelet being dominated by the larger acoustic impedance contrast produced from the Namur Sandstone. The McKinlay Member depth structure was mapped using various depth conversion methods to investigate the uncertainty in the depth structure expected for the landing of the well and along the lateral section. An average depth surface generated from the different techniques was useful for providing the general form of the structure and was used to predict dip changes along the lateral section. Understanding the uncertainty led to successful well placement of the first horizontal well in the McKinlay Member on the Western Flank.
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