Statistical downscaling with spatial misalignment: Application to wildland fire PM2.5_{2.5} concentration forecasting

Fine particulate matter, PM$_{2.5}$, has been documented to have adverse health effects and wildland fires are a major contributor to PM$_{2.5}$ air pollution in the US. Forecasters use numerical models to predict PM$_{2.5}$ concentrations to warn the public of impending health risk. Statistical methods are needed to calibrate the numerical model forecast using monitor data to reduce bias and quantify uncertainty. Typical model calibration techniques do not allow for errors due to misalignment of geographic locations. We propose a spatiotemporal downscaling methodology that uses image registration techniques to identify the spatial misalignment and accounts for and corrects the bias produced by such warping. Our model is fitted in a Bayesian framework to provide uncertainty quantification of the misalignment and other sources of error. We apply this method to different simulated data sets and show enhanced performance of the method in the presence of spatial misalignment. Finally, we apply the method to a large fire in Washington state and show that the proposed method provides more realistic uncertainty quantification than standard methods

Duplex ultrasound in aneurysm surveillance following endovascular aneurysm repair: a comparison with computed tomography aortography

ObjectivesCumulative radiation dose, cost, and increased demand for computed tomography aortography (CTA) suggest that duplex ultrasonography (DU) may be an alternative to CTA-based surveillance. We compared CTA with DU during endovascular aneurysm repair (EVAR) follow-up.MethodsPatients undergoing EVAR had clinical and radiological follow-up data entered in a prospectively maintained database. For the purpose of this study, the gold standard test for endoleak detection was CTA, and an endoleak detected on DU alone was assumed to be a false positive result. DU interpretation was performed independently of CTA and vice versa.ResultsOne hundred thirty-two patients underwent EVAR, of whom 117 attended for follow-up ranging from six months to nine years (mean, 32 months). Adequate aneurysm sac visualisation on DU was not possible in 1.7% of patients, predominantly due to obesity. Twenty-eight endoleaks were detected in 28 patients during follow-up. Of these, 24 were initially identified on DU (four false negative DU examinations), and eight had at least one negative CTA with a positive DU prior to diagnosis. Twenty-three endoleaks were type II in nature and three of these patients had increased sac size. There was one type I and four type III endoleaks. Two of these (both type III) had an increased sac size. Of 12 patients with increased aneurysm size of 5 mm or more at follow-up, five had an endoleak visible on DU, yet negative CTA and a further five had endoleak visualisation on both DU and CTA. Of six endoleaks which underwent re-intervention, all were initially picked up on DU. One of these endoleaks was never demonstrated on CTA and a further two had at least one negative CTA prior to endoleak confirmation. Positive predictive value for DU was 45% and negative predictive value 94%. Specificity of DU for endoleak detection was 67% when compared with CTA, because of the large number of false positive DU results. Sensitivity for DU was 86%, with all clinically significant endoleaks demonstrated on CTA also detected on DU.ConclusionDespite its low positive predictive value, we found DU to be a sensitive test for the detection of clinically significant endoleaks. Given concerns about cumulative radiation exposure and cost, and the surprisingly low sensitivity of CTA for endoleak detection in this series, selective CTA based on DU surveillance may be a more appropriate long-term strategy

Metrics for aggregating the climate effect of different emissions: A unifying framework

Multi-gas approaches to climate change policies require a metric establishing equivalences among emissions of various species. Climate scientists and economists have proposed four classes of such metrics and debated their relative merits. We present a unifying framework that clarifies the relationships among them. We show that the Global Warming Potential, used in international law to compare greenhouse gases, is a special case of the Global Damage Potential, assuming (1) a finite time horizon, (2) a zero discount rate, (3) constant atmospheric concentrations, and (4) impacts that are proportional to radiative forcing. We show that the Global Temperature change Potential is a special case of the Global Cost Potential, assuming (1) no induced technological change, and (2) a short-lived capital stock. We also show that the Global Cost Potential is a special case of the Global Damage Potential, assuming (1) zero damages below a threshold and (2) infinite damage after a threshold. The UN Framework Convention on Climate Change uses the Global Warming Potential, a simplified cost-benefit concept, even though the UNFCCC frames climate policy as a cost-effectiveness problem and should therefore use the Global Cost Potential or its simplification, the Global Temperature Potential

New-Onset Atrial Fibrillation After Aortic Valve Replacement Comparison of Transfemoral, Transapical, Transaortic, and Surgical Approaches

ObjectivesThis study sought to determine the incidence of new-onset atrial fibrillation (AF) associated with different methods of isolated aortic valve replacement (AVR)—transfemoral (TF), transapical (TA), and transaortic (TAo) catheter-based valve replacement and conventional surgical approaches.BackgroundThe relative incidences of AF associated with the various access routes for AVR have not been well characterized.MethodsIn this single-center, retrospective cohort study, we evaluated a total of 231 consecutive patients who underwent AVR for degenerative aortic stenosis (AS) between March 2010 and September 2012. Patients with a history of paroxysmal, persistent, or chronic AF, with bicuspid aortic valves, and patients who died within 48 h after AVR were excluded. A total of 123 patients (53% of total group) qualified for inclusion. Data on documented episodes of new-onset AF, along with all clinical, echocardiographic, procedural, and 30-day follow-up data, were collated.ResultsAF occurred in 52 patients (42.3%). AF incidence varied according to the procedural method. AF occurred in 60% of patients who underwent surgical AVR (SAVR), in 53% after TA-TAVR, in 33% after TAo-TAVR cases, and 14% after TF-TAVR. The episodes occurred at a median time interval of 53 (25th to 75th percentile, 41 to 87) h after completion of the procedure. Procedures without pericardiotomy had an 82% risk reduction of AF compared with those with pericardiotomy (adjusted odds ratio: 0.18; 95% confidence interval: 0.05 to 0.59).ConclusionsAF was a common complication of AVR with a cumulative incidence of >40% in elderly patients with degenerative AS who underwent either SAVR or TAVR. AF was most common with SAVR and least common with TF-TAVR. Procedures without pericardiotomy were associated with a lower incidence of AF

Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus

Aim: The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza. Results: We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay. A total of eight analogs showed IC50s in the range of 0.14–5.0 μM. Additionally a quantitative structure–property relationship study showed high correlation between experimental and predicted activity based on a molecular descriptor set. Conclusion: A range of thiazolides show useful activity against an H1N1 strain of IAV. Further evaluation of these molecules as potential new small molecule therapies is justified

Inhibition of Plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites

The malaria parasite Plasmodium falciparum exports several hundred proteins into the infected erythrocyte that are involved in cellular remodeling and severe virulence. The export mechanism involves the Plasmodium export element (PEXEL), which is a cleavage site for the parasite protease, Plasmepsin V (PMV). The PMV gene is refractory to deletion, suggesting it is essential, but definitive proof is lacking. Here, we generated a PEXEL-mimetic inhibitor that potently blocks the activity of PMV isolated from P. falciparum and Plasmodium vivax. Assessment of PMV activity in P. falciparum revealed PEXEL cleavage occurs cotranslationaly, similar to signal peptidase. Treatment of P. falciparum-infected erythrocytes with the inhibitor caused dose-dependent inhibition of PEXEL processing as well as protein export, including impaired display of the major virulence adhesin, PfEMP1, on the erythrocyte surface, and cytoadherence. The inhibitor killed parasites at the trophozoite stage and knockdown of PMV enhanced sensitivity to the inhibitor, while overexpression of PMV increased resistance. This provides the first direct evidence that PMV activity is essential for protein export in Plasmodium spp. and for parasite survival in human erythrocytes and validates PMV as an antimalarial drug target