31 research outputs found

    Creation of Laryngeal Grafts from Primary Human Cells and Decellularized Laryngeal Scaffolds

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    Current reconstruction methods of the laryngotracheal segment fail to replace the complex functions of the human larynx. Bioengineering approaches to reconstruction have been limited by the complex tissue compartmentation of the larynx. We attempted to overcome this limitation by bio-engineering laryngeal grafts from decellularized canine laryngeal scaffolds recellularized with human primary cells under one uniform culture medium condition. First, we generated laryngeal scaffolds with preserved glycosaminoglycan content and biomechanical properties by detergent perfusion-decellularization over nine days. We proofed biocompatibility by absence of a CD3 lymphocyte response to subcutaneously implanted scaffolds in immune-competent rats. We then developed a uniform culture medium that strengthened the endothelial barrier over 5 days after an initial growth phase. Simultaneously, this culture medium supported airway epithelial cell and skeletal myoblast growth while maintaining their full differentiation and maturation potential. We then applied the uniform culture medium composition to whole laryngeal scaffolds seeded with endothelial cells from both carotid arteries and external jugular veins and generated re-endothelialized arterial and venous vascular beds. Under the same culture medium condition, we bio-engineered epithelial monolayers onto laryngeal mucosa and repopulated intrinsic laryngeal muscle. We were then able to demonstrate early muscle formation in heterotopic transplantations in immuno-deficient mice. The model supported the formation of three humanized laryngeal tissue compartments under one uniform culture condition, possibly a key factor in developing, complex, multicellular, ready-to-transplant tissue grafts

    Pre-hospital ECG for acute coronary syndrome in urban India: A cost-effectiveness analysis

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    <p>Abstract</p> <p>Background</p> <p>Patients with acute coronary syndrome (ACS) in India have increased pre-hospital delay and low rates of thrombolytic reperfusion. Use of ECG could reduce pre-hospital delay among patients who first present to a general practitioner (GP). We assessed whether performing ECG on patients with acute chest pain would improve long-term outcomes and be cost-effective.</p> <p>Methods</p> <p>We created a Markov model of urban Indian patients presenting to a GP with acute chest pain to compare a GP's performing an ECG versus not performing one. Variables describing the accuracy of a GP's referral decision in chest pain and ACS, ACS treatment patterns, the effectiveness of thrombolytic reperfusion, and costs were derived from Indian data where available and other developed world studies. The model was used to estimate the incremental cost-effectiveness ratio (ICER) of the intervention in 2007 US dollars per quality adjusted life years (QALY) gained.</p> <p>Results</p> <p>Under baseline assumptions, the ECG strategy cost an additional 12.65perQALYgainedcomparedtonoECG.SensitivityanalysesaroundthecostoftheECG,costofthrombolytic,andreferralaccuracyoftheGPyieldedICERsfortheECGstrategyrangingbetweencostsavingand12.65 per QALY gained compared to no ECG. Sensitivity analyses around the cost of the ECG, cost of thrombolytic, and referral accuracy of the GP yielded ICERs for the ECG strategy ranging between cost-saving and 1124/QALY. All results indicated the intervention is cost-effective under current World Health Organization recommendations.</p> <p>Conclusions</p> <p>While direct presentation to the hospital with acute chest pain is preferable, in urban Indian patients presenting first to a GP, an ECG performed by the GP is a cost-effective strategy to reduce disability and mortality. This strategy should be clinically studied and considered until improved emergency transport services are available.</p

    Characterization of the Sedimentation Associated with the \u3cem\u3eDeepwater Horizon\u3c/em\u3e Blowout: Depositional Pulse, Initial Response, and Stabilization

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    The Deepwater Horizon (DWH) blowout led to a depositional pulse in the northeast Gulf of Mexico in the Fall of 2010 associated with an observed Marine Oil Snow Sedimentation and Flocculent Accumulation (MOSSFA) event. A time series (2010–2016) of annually collected sediment cores at four sites characterize the sedimentary response to the event, post-event, and stabilization/recovery. The depositional pulse (2010–2011) was characterized by high sedimentation rates with little to no bioturbation and large excursions in % silt. The lack of changes in sediment composition indicate that the same sediment sources dominated during the event, but the rates of sedimentation increased. In the years following the event (2011–2012), sedimentation rates were lower, and bioturbation was absent, and the initial excursions in % silt began to become undetectable in the sedimentary record. Between 2013 and 2016, a spatially and temporally variable return of bioturbation was detected at most sites. Sedimentation rates at all sites remained low, but increases in 234Thxs apparent mass accumulation rates indicated a return of bioturbation and potential stabilization and/or recovery of the sedimentary system. The deepest site (~1500 m) did not have any indication of bioturbation as of the 2016 collections, which may reflect a lack of recovery or that bioturbation was never present. In 2012, 210Pbxs age dating began to resolve the depositional pulse suggesting it may be applied to determine changes in the pulse deposit over time, and/or its preservation in the sedimentary record. Factors that may influence preservation include burial, bioturbation, degradation of the pulse signature, and remobilization of pulse sediments
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