Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic (n = 39), sham-septic (n = 16), and healthy (n = 24) animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy

Estimation of forest structure and canopy fuel parameters from small-footprint full-waveform LiDAR data

Precise knowledge of fuel conditions is important for predicting fire hazards and simulating fire growth and intensity across the landscape. We present a methodology to retrieve and map forest canopy fuel and other forest structural parameters using small-footprint full-waveform airborne light detection and ranging (LiDAR) data. Full-waveform LiDAR sensors register the complete returned backscattered signal through time and can describe physical properties of the intercepted objects. This study was undertaken in a mixed forest dominated by Douglas-fir, occasionally mixed with other conifers, in north-west Oregon (United States). We extracted two sets of LiDAR metrics using pulse detection and waveform modelling and then constructed several predictive models using forward stepwise multiple linear regression. The resulting models explained ~80% of the variability for many of the canopy fuel and forest structure parameters: aboveground biomass (R2 = 0.84), quadratic mean diameter (R2 = 0.82), canopy height (R2 = 0.79), canopy base height (R2 = 0.78) and canopy fuel load (R2 = 0.79). The lowest performing models included basal area (R2 = 0.76), stand volume (R2 = 0.73), canopy bulk density (R2 = 0.67) and stand density index (R2 = 0.66). Our results indicate that full-waveform LiDAR systems show promise in systematically characterising the structure and canopy fuel loads of forests, which may enable accurate fire behaviour forecasting that in turn supports the development of prevention and planning policies.This paper was developed as a result of two mobility grants funded by the Erasmus Mundus Programme of the European Commission under the Transatlantic Partnership for Excellence in Engineering (TEE Project) and the Generalitat Valenciana (BEST/2012/235). The authors appreciate the financial support provided by the Spanish Ministry of Science and Innovation in the framework of the project CGL2010-19591/BTE. In addition, the authors thank the Panther Creek Remote Sensing and Research cooperative program for the data provided for this research, Jim Flewelling (Seattle Biometrics) and George McFadden (Bureau of Land Management) for their help in data availability and preparation.Hermosilla Gómez, T.; Ruiz Fernández, LÁ.; Kazakova, AN.; Coops, N.; Moskal, LM. (2014). Estimation of forest structure and canopy fuel parameters from small-footprint full-waveform LiDAR data. International Journal of Wildland Fire. 23(2):224-233. https://doi.org/10.1071/WF13086S224233232Akaike, H. (1974). A new look at the statistical model identification. IEEE Transactions on Automatic Control, 19(6), 716-723. doi:10.1109/tac.1974.1100705Andersen, H.-E., McGaughey, R. J., & Reutebuch, S. E. (2005). Estimating forest canopy fuel parameters using LIDAR data. 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Assessing canopy fuel stratum characteristics in crown fire prone fuel types of western North America. International Journal of Wildland Fire, 12(1), 39. doi:10.1071/wf02024Drake, J. B., Dubayah, R. O., Clark, D. B., Knox, R. G., Blair, J. B., Hofton, M. A., … Prince, S. (2002). Estimation of tropical forest structural characteristics using large-footprint lidar. Remote Sensing of Environment, 79(2-3), 305-319. doi:10.1016/s0034-4257(01)00281-4Erdody, T. L., & Moskal, L. M. (2010). Fusion of LiDAR and imagery for estimating forest canopy fuels. Remote Sensing of Environment, 114(4), 725-737. doi:10.1016/j.rse.2009.11.002Falkowski, M. J., Gessler, P. E., Morgan, P., Hudak, A. T., & Smith, A. M. S. (2005). Characterizing and mapping forest fire fuels using ASTER imagery and gradient modeling. Forest Ecology and Management, 217(2-3), 129-146. doi:10.1016/j.foreco.2005.06.013Flannigan, M. ., Stocks, B. ., & Wotton, B. . (2000). Climate change and forest fires. 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Geophysical Research Letters, 32(21). doi:10.1029/2005gl023471Heinzel, J., & Koch, B. (2011). Exploring full-waveform LiDAR parameters for tree species classification. International Journal of Applied Earth Observation and Geoinformation, 13(1), 152-160. doi:10.1016/j.jag.2010.09.010Höfle, B., Hollaus, M., & Hagenauer, J. (2012). Urban vegetation detection using radiometrically calibrated small-footprint full-waveform airborne LiDAR data. ISPRS Journal of Photogrammetry and Remote Sensing, 67, 134-147. doi:10.1016/j.isprsjprs.2011.12.003HYDE, P., DUBAYAH, R., PETERSON, B., BLAIR, J., HOFTON, M., HUNSAKER, C., … WALKER, W. (2005). Mapping forest structure for wildlife habitat analysis using waveform lidar: Validation of montane ecosystems. Remote Sensing of Environment, 96(3-4), 427-437. doi:10.1016/j.rse.2005.03.005Keane, R. E., Burgan, R., & van Wagtendonk, J. (2001). Mapping wildland fuels for fire management across multiple scales: Integrating remote sensing, GIS, and biophysical modeling. International Journal of Wildland Fire, 10(4), 301. doi:10.1071/wf01028Kim, Y., Yang, Z., Cohen, W. B., Pflugmacher, D., Lauver, C. L., & Vankat, J. L. (2009). Distinguishing between live and dead standing tree biomass on the North Rim of Grand Canyon National Park, USA using small-footprint lidar data. Remote Sensing of Environment, 113(11), 2499-2510. doi:10.1016/j.rse.2009.07.010Koetz, B., Morsdorf, F., Sun, G., Ranson, K. J., Itten, K., & Allgower, B. (2006). Inversion of a Lidar Waveform Model for Forest Biophysical Parameter Estimation. IEEE Geoscience and Remote Sensing Letters, 3(1), 49-53. doi:10.1109/lgrs.2005.856706Lefsky, M. A., Cohen, W. B., Acker, S. A., Parker, G. G., Spies, T. A., & Harding, D. (1999). Lidar Remote Sensing of the Canopy Structure and Biophysical Properties of Douglas-Fir Western Hemlock Forests. 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Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Estimating Exposome Score for Schizophrenia Using Predictive Modeling Approach in Two Independent Samples: The Results From the EUGEI Study

Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic "risk" and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke's R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P < .001), patients from siblings (OR = 1.58, P < .001), and siblings from controls (OR = 1.21, P = .001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome

White Noise Speech Illusions: A Trait-Dependent Risk Marker for Psychotic Disorder?

Introduction: White noise speech illusions index liability for psychotic disorder in case-control comparisons. In the current study, we examined i) the rate of white noise speech illusions in siblings of patients with psychotic disorder and ii) to what degree this rate would be contingent on exposure to known environmental risk factors (childhood adversity and recent life events) and level of known endophenotypic dimensions of psychotic disorder [psychotic experiences assessed with the Community Assessment of Psychic Experiences (CAPE) scale and cognitive ability]. Methods: The white noise task was used as an experimental paradigm to elicit and measure speech illusions in 1,014 patients with psychotic disorders, 1,157 siblings, and 1,507 healthy participants. We examined associations between speech illusions and increasing familial risk (control -> sibling -> patient), modeled as both a linear and a categorical effect, and associations between speech illusions and level of childhood adversities and life events as well as with CAPE scores and cognitive ability scores. Results: While a positive association was found between white noise speech illusions across hypothesized increasing levels of familial risk (controls -> siblings -> patients) [odds ratio (OR) linear 1.11, 95% confidence interval (CI) 1.02-1.21, p = 0.019], there was no evidence for a categorical association with sibling status (OR 0.93, 95% CI 0.79-1.09, p = 0.360). The association between speech illusions and linear familial risk was greater if scores on the CAPE positive scale were higher (p interaction = 0.003; ORlow CAPE positive scale 0.96, 95% CI 0.85-1.07; ORhigh CAPE positive scale 1.26, 95% CI 1.09-1.46); cognitive ability was lower (p interaction < 0.001; ORhigh cognitive ability 0.94, 95% CI 0.84-1.05; ORlow cognitive ability 1.43, 95% CI 1.23-1.68); and exposure to childhood adversity was higher (p interaction < 0.001; ORlow adversity 0.92, 95% CI 0.82-1.04; ORhigh adversity 1.31, 95% CI 1.13-1.52). A similar, although less marked, pattern was seen for categorical patient-control and sibling-control comparisons. Exposure to recent life events did not modify the association between white noise and familial risk (p interaction = 0.232). Conclusion: The association between white noise speech illusions and familial risk is contingent on additional evidence of endophenotypic expression and of exposure to childhood adversity. Therefore, speech illusions may represent a trait-dependent risk marker

Wage inequality, segregation by skill and the price of capital in an assignment model

Some pieces of empirical evidence suggest that in the U.S., over the last few decades, (i) wage inequality between-plants has risen much more than wage inequality within-plants and (ii) there has been an increase in the segregation of workers by skill into separate plants. This paper presents a frictionless assignment model in which these two features can be explained simultaneously as the result of the decline in the relative price of capital. Additional implications of the model regarding the skill premium and the dispersion in labor productivity across plants are also consistent with the empirical evidence. [resumen de autor