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Background We assessed the cost-effectiveness of boceprevir-based triple therapy compared to peginterferon alpha and ribavirin dual therapy in untreated patients with genotype 1 chronic hepatitis C; patients were discriminated according to the combination of baseline plus on-treatment predictors of boceprevir-based triple therapy. Methods Cost-effectiveness analysis performed according to data from the available published literature. The target population was composed of untreated Caucasian patients, aged 50 years, with genotype 1 chronic hepatitis C, and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euro, at 2013 value), life-years gained, quality-adjusted life year, and incremental cost-effectiveness ratio. The robustness of the results was evaluated by multivariable probabilistic sensitivity analyses. Results According to the baseline predictors of sustained virological response (genotype 1b, low viral load, fibrosis F0-F3, and body mass index) and the 1 Log drop of HCV-RNA after the dual therapy lead-in period, boceprevir was cost-effective in different patient profiles. Conclusions In untreated genotype 1b chronic hepatitis C patients, the cost-effectiveness of boceprevir-based triple therapy widely ranges according to different profiles of sustained virological response predictors, allowing optimization and personalization of triple therapy. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, starting from a multivariate spatio-temporal array, containing air pollution data collected for the main pollutants at different monitoring sites over a 1-year period, a new approach is proposed to get a Multipollutant-Multisite Air Quality Index (AQI) time series. A two steps aggregation, related to space and to pollutants, is considered. For the first aggregation (spatial synthesis) a PCA is performed on data array opportunely rearranged, while the index I 2, proposed in Ruggieri and Plaia (2011), is used for the second aggregation (pollutant synthesis), obtaining the new index . Daily data of four air pollutants from the city of Palermo (Italy) are analyzed to test the performance of the new index. The index overcomes the main issues presented by other indices, many of which based on AQI computed by US EPA, considering the highest pollutant concentration adequately standardized. The comparison carried out shows that the index here proposed has a better performance than the synthesis by median-maximum (Bruno and Cocchi, 2002) and the synthesis by PCA along both space and pollutant dimensions, if the conjoint effect on air quality of the different pollutants has to be taken into account. [Copyright &y& Elsevier]

Background: The benefit of sublingual immunotherapy (SLIT) with grass allergens for seasonal allergic rhinitis has been extensively studied, but data on efficacy are still equivocal. Objective: To assess the effectiveness of SLIT with grass allergens in the reduction of symptoms and medication in patients with seasonal allergic rhinitis to grass pollen. Methods: Computerized bibliographic searches of MEDLINE (1995-2010) were supplemented by hand searches of reference lists. Studies were included if they were double-blind randomized controlled trials (RCTs) comparing SLIT to placebo and if they included patients with history of allergy to grass pollen treated with natural grass pollen extracts. Nineteen RCTs with 2971 patients were analyzed. The outcomes assessed were symptom and medication scores. Results: Using a random-effects model, SLIT with grass allergens significantly reduces both symptoms (standardized mean difference, –0.32; 95% CI, –0.44 to –0.21) and medication use (standardized mean difference, –0.33; 95% CI, –0.50 to –0.16) compared with placebo. The treatment is more efficacious in adults than in children. Prolonging duration of preseasonal treatment for more than 12 weeks improves the treatment efficacy. Conclusion: This meta-analysis found that SLIT with grass allergens is effective in patients with seasonal allergic rhinitis compared with placebo. The benefit is clinically modest, and criteria are needed to identify patients most likely to benefit from SLIT. [Copyright &y& Elsevier]

Abstract: Missing data represent a general problem in many scientific fields above all in environmental research. Several methods have been proposed in literature for handling missing data and the choice of an appropriate method depends, among others, on the missing data pattern and on the missing-data mechanism. One approach to the problem is to impute them to yield a complete data set. The goal of this paper is to propose a new single imputation method and to compare its performance to other single and multiple imputation methods known in literature. Considering a data set of concentration measured every by eight monitoring stations distributed over the metropolitan area of Palermo, Sicily, during 2003, simulated incomplete data have been generated, and the performance of the imputation methods have been compared on the correlation coefficient , the index of agreement (d), the root mean square deviation (RMSD) and the mean absolute deviation (MAD). All the performance indicators agree to evaluate the proposed method as the best among the ones compared, independently on the gap length and on the number of stations with missing data. [Copyright &y& Elsevier]

To date, no stem cell therapy has been directed to specific recipients—and, conversely, withheld from others—based on a clinical or molecular profile congruent with that cell's therapeutic mechanism-of-action (MOA) for that condition. We address this challenge preclinically with a prototypical scenario: human neural stem cells (hNSCs) against perinatal/neonatal cerebral hypoxic-ischemic injury (HII). We demonstrate that a clinically translatable magnetic resonance imaging (MRI) algorithm, hierarchical region splitting, provides a rigorous, expeditious, prospective, noninvasive "biomarker" for identifying subjects with lesions bearing a molecular profile indicative of responsiveness to hNSCs' neuroprotective MOA. Implanted hNSCs improve lesional, motor, and/or cognitive outcomes only when there is an MRI-measurable penumbra that can be forestalled from evolving into necrotic core; the core never improves. Unlike the core, a penumbra is characterized by a molecular profile associated with salvageability. Hence, only lesions characterized by penumbral > core volumes should be treated with cells, making such measurements arguably a regenerative medicine selection biomarker. • Biomarkers are needed to predict responders versus non-responders to cell therapy • Stem cells rescue the penumbra of a cerebral infarct, but not the necrotic core • MRI, by quantifying the penumbra, identifies niches molecularly receptive to cells • Only lesions with a penumbra > core are amenable to this neuroprotective mechanism Regenerative medicine awaits a biomarker for predicting patients responsive to a stem cell's therapeutic mechanism-of-action. Hartman et al. show that MRI, in quantifying the penumbra within a cerebral infarct, identifies the niche molecularly receptive to cell-mediated neuroprotection, suggesting that, for cases with a low penumbra-to-core ratio, cell therapy is not indicated. [ABSTRACT FROM AUTHOR]

Objective Neural stem cell transplantation is now being evaluated for treatment of neonatal cerebral hypoxic-ischemic injury (HII), as there is compelling evidence in animal models that it contributes to the repair of multiple delayed/secondary injuries. We sought to determine in a model of rat pup HII model whether delayed stem cell transplantation improved structural and functional recoveries and whether this was due primarily to rescue of penumbral tissue. Methods We transplanted human NSCs (hNSCs) into the contralateral ventricle of a 10 day-old rat pup 3 days post-unilateral HII, exploiting the cell's intrinsic pathotropism to direct them to the lesioned area which would not be hospitable to direct implantation. Using high field magnetic resonance imaging at 2d and 90d post-HII, we examined total lesion, core, and penumbral volumes. Behavior was evaluated at 90d post-HII followed by histological and immunohistochemical examination of brain tissue. Results At both time points, total lesion and penumbral volumes were smaller in animals treated with hNSCs; the necrotic core, as expected, remained unchanged. Activity levels were increased and working memory was improved in animals treated with hNSCs. Conclusion Our data demonstrate that, at least 3 days after injury, there is potentially salvageable cerebral tissue in the penumbra following HII and that hNSC-mediated rescue of that tissue is associated with improved long-term motor and cognitive outcomes. These findings reinforce the speculation that NSCs may be uniquely beneficial for neurorepair in later stages of neonatal HII. Specifically, such intervention should be able to be instituted after 3 days of hypothermia treatment, presently the immediate standard-of-care for HII, allowing for the possibility of synergistic neuroprotective therapies. [Supported by grants from the NIHNINDS–1RO1NS059770-01A2) and the Department of Pediatrics, Loma Linda University School of Medicine]. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous (SCIT) and sublingual (SLIT) immunotherapy are the 2 most prescribed routes for administering allergen-specific immunotherapy. They were shown to be effective in control of symptoms and in reducing rescue medication use in patients with allergic diseases, but their effectiveness has to be balanced against side effects. In recent years, SLIT has been increasingly prescribed, instead of SCIT, because of improved safety and easy administration. Objective: We assessed which route is the most effective in the treatment of patients with seasonal allergic rhinitis to grass pollen. Methods: An indirect meta-analysis–based comparison between SCIT and SLIT was performed. Treatment efficacy was determined as the standardized mean difference (SMD) in symptom and medication scores obtained with active treatment, SCIT or SLIT, compared with placebo. Studies were included if they were double-blind randomized controlled trials comparing SCIT or SLIT with placebo. Thirty-six randomized controlled trials (3014 patients; 2768 controls) were analyzed. Results: The overall effect size of SCIT for symptom score (SMD, −0.92; 95%CI, −1.26 to −0.58) was significantly higher than SLIT, both administered via drops (SMD, −0.25; 95% CI, −0.45 to −0.05) and tablets (SMD, −0.40; 95%CI, −0.54 to −0.27). Similar results were reported for medication score (SCIT: SMD, −0.58; 95% CI, −0.86 to −0.30. SLIT drops: SMD, −0.37; 95% CI, −0.74 to −0.00. SLIT tablets SMD, −0.30; 95% CI, −0.44 to −0.16). Conclusions: Our results provide indirect but solid evidence that SCIT is more effective than SLIT in controlling symptoms and in reducing the use of antiallergic medications in seasonal allergic rhinoconjuntivitis to grass pollen. [ABSTRACT FROM AUTHOR]

A combined experimental and numerical investigation on the effects of H2 addition to lean-premixed CH4 flames in highly strained counterflow fields (with strain rates up to 8000 s−1) using preheated flows indicate significant enhancement of lean flammability limits and extinction strain rates for relatively small amounts of H2 addition. Numerical modeling of the counterflow opposed jet configuration used in this study indicated extinction strain rates which were within 5% of experimentally measured values for equivalence ratios ranging from 0.75 to less than 0.4. Both experimental and numerical results indicate that increasing H2 in the fuel significantly increases flame speeds and thus extinction strain rates. Furthermore, increasing H2 decreases the dependency of extinction equivalence ratio on the strain rate of the flow. For all of the mixtures investigated, extinction temperatures depend primarily on equivalence ratio and not fuel composition for the range of H2 content studied, which suggests that extinction can be correlated to flame temperature and O2 concentration. Nonetheless, H2 addition greatly increases the maximum allowable strain rate before extinction temperatures are reached. Inspection of the model-predicted species profiles suggest that the enhancement of CH4 burning rates with H2 addition is driven by early H2 breakdown increasing radical production rates early in the flame zone to enhance CH4 ignition under conditions where otherwise CH4 combustion might be prone to undergo extinction. [Copyright &y& Elsevier]

This 2-year study, performed in a typical Mediterranean environment on three soil types (two Inceptisols and one Vertisol), aimed to improve understanding of the factors that play a major role in determining crop response when soil management shifts from conventional tillage (CT) to no-tillage (NT). The effects of NT on the soil nitrogen (N) availability, N uptake, 15 N fertilizer recovery, and grain yield of durum wheat were evaluated in comparison to CT under five different N fertilization rates (0, 40, 80, 120, and 160 kg N ha −1 ). Compared to CT, NT negatively affected grain yield in one of the two years but only in the two Inceptisols. On average, a considerable grain yield advantage of CT over NT (approximately +0.6 Mg ha −1 of grain) was observed with no N fertilization. This benefit decreased progressively when N fertilizer rate increased to the point that at 120 kg ha −1 of N applied differences between CT and NT were negligible. The differences between the two tillage systems in both grain yield and N uptake were attributable more to differences in the native soil mineral N (that materialized already during the vegetative phase of the crop cycle) than to differences between CT plants and NT plants in efficiency in taking up N from fertilizer. The differences between CT and NT for many of the traits observed in durum wheat plants increased with decreasing soil fertility and in particular with decreasing soil total N. In conclusion, the shift from CT to NT, which should be accompanied in any case by an increase in the N fertilization rate to take into account the reduction in soil N available for the crop, was less problematic in the Vertisol, which is more fertile and better structured than the two Inceptisols. [ABSTRACT FROM AUTHOR]

As part of the Ocean Margins Program (OMP), organic carbon 14C measurements have been made on benthic fauna and kasten core sediments from the North Carolina continental slope. These analyses are used to evaluate the nature and burial flux of organic matter in the OMP study area off Cape Hatteras. Despite the fact that surface sediment 14C contents ranged from −41 to −215 per mil, the benthic fauna (primarily polychaetes) all contained significant amounts of bomb-14C (body tissue 14C contents ranging from +20 to +82 per mil). Bomb-14C clearly is reaching the seabed on the North Carolina slope, and the labile planktonic material carrying this signal is a primary source of nutrition to the benthic ecosystem. The enrichment of 14C in benthic faunal tissue relative to the 14C content of bulk surface-sediment organic matter (a difference of ∼150 per mil) is attributed to a combination of particle selection and selective digestive processes. Organic carbon burial rates from 12 stations on the North Carolina slope varied from 0.02 to 1.7 mol of C m−2 yr−1, with a mean value of 0.7 mol of C m−2 yr−1. The accumulation of organic matter on the upper slope accounts for <1% of the primary production in the entire continental margin system. The North Carolina margin was deliberately selected because of its potential for offshore transport and high sediment deposition rates, and even in this environment, burial of organic carbon accounts for a very small fraction of the primary production occurring in surface waters. [Copyright &y& Elsevier]