Integration of Unmanned Aerial Systems in Class E Airspace: The Effect on Air Traffic Controller Workload

As technology rapidly advances and our imagination is no longer fantasy but instead reality, the aviation community needs to concentrate on the harsh truth of airspace safety. In the situation of integrating unmanned aerial systems (UASs) into the National airspace, UASs outside of terminal areas would generally be permitted to fly their preferred routes, and self-separate, with minimal intervention from air traffic control. From an air traffic control perspective, the integration could raise a number of human performance problems including workload extremes and passive-monitoring demands. One fundamental requirement for operation in the National Air Space is to preserve the safety of the general public. This paper describes an experimental evaluation of the effect different levels of UAS intent information has on air traffic controller workload. The simulation specifically manipulates intent sharing, that is, whether unmanned aerial vehicles provided advance notice of their intended maneuvers. The Effects on air traffic controller workload when control capability is altered were also explored

Modeling Viscosity and Density of Ethanol-Diesel-Biodiesel Ternary Blends for Sustainable Environment

Rapid depletion in fossil fuels, inflation in petroleum prices, and rising energy demand have forced towards alternative transport fuels. Among these alternative fuels, diesel-ethanol and diesel-biodiesel blends gain the most attention due to their quality characteristics and environmentally friendly nature. The viscosity and density of these biodiesel blends are slightly higher than diesel, which is a significant barrier to the commercialization of biodiesel. In this study, the density and viscosity of 30 different ternary biodiesel blends was investigated at 15 °С and 40 °С, respectively. Different density and viscosity models were developed and tested on biodiesel blends soured from different feedstock’s including palm, coconut, soybean, mustard, and calophyllum oils. The prognostic ability and precisions of these developed models was assessed statistically using Absolute Percentage Error (APE) and Mean Absolute Percentage Error (MAPE). The MAPE of 0.045% and 0.085% for density model and 1.85%, 1.41%, 3.48% and 2.27%, 1.85%, 3.50% for viscosity models were obtained on % volume and % mass basis. These developed correlations are useful for ternary biodiesel blends where alcohols are the part of biodiesel blends. The modeled values of densities and viscosities of ternary blends were significantly comparable with the measured densities and viscosities, which are feasible to avoid the harm of vehicles’ operability

Clinical Impact of Tumour DNA Repair Expression and T-cell Infiltration in Breast Cancers

Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand break repair (BRCA1, BLM, WRN, RECQL4, RECQL5, TOPO2A, DNA-PKcs, Ku70/Ku80), nucleotide excision repair (ERCC1), base excision repair (XRCC1, pol β, FEN1, PARP1), and immune responses (CD8, PD-1, PD-L1, FOXP3) in 1,269 breast cancers and validated our findings in an independent estrogen receptor–negative (ER−) cohort (n = 279). Patients with tumors that expressed low XRCC1, low ATM, and low BRCA1 were not only associated with high numbers of CD8+ tumor-infiltrating lymphocytes, but were also linked to higher grades, high proliferation indexes, presence of dedifferentiated cells, ER− cells, and poor survival (all P ≤ 0.01). PD-1+ or PD-L1+ breast cancers with low XRCC1 were also linked to an aggressive phenotype that was high grade, had high proliferation indexes, contained dedifferentiated cells and ER− (all with P values ≤ 0.01), and poor survival (P = 0.00021 and P = 0.00022, for PD-1+ and PD-L1+ cancers, respectively) including in an independent ER− validation cohort (P = 0.007 and P = 0.047, respectively). We conclude that the interplay between DNA repair, CD8, PD-L1, and PD-1 can promote aggressive tumor phenotypes. XRCC1-directed personalization of immune checkpoint inhibitor therapy may be feasible and warrants further investigation in breast cancer. Cancer Immunol Res; 5(4); 292–9. ©2017 AACR

Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy.

After allotransplantation, cytomegalovirus (CMV) may be transmitted from the donor organ, giving rise to primary infection in a CMV negative recipient or reinfection in one who is CMV positive. In addition, latent CMV may reactivate in a CMV positive recipient. In this study, serial blood samples from 689 kidney or liver transplant recipients were tested for CMV DNA by quantitative PCR. CMV was managed using preemptive antiviral therapy and no patient received antiviral prophylaxis. Dynamic and quantitative measures of viremia and treatment were assessed. Median peak viral load, duration of viremia and duration of treatment were highest during primary infection, followed by reinfection then reactivation. In patients who experienced a second episode of viremia, the viral replication rate was significantly slower than in the first episode. Our data provide a clear demonstration of the immune control of CMV in immunosuppressed patients and emphasize the effectiveness of the preemptive approach for prevention of CMV syndrome and end organ disease. Overall, our findings provide quantitative biomarkers which can be used in pharmacodynamic assessments of the ability of novel CMV vaccines or antiviral drugs to reduce or even interrupt such transmission

Cytomegalovirus viral load parameters associated with earlier initiation of pre-emptive therapy after solid organ transplantation

BACKGROUND: Human cytomegalovirus (HCMV) can be managed by monitoring HCMV DNA in the blood and giving valganciclovir when viral load exceeds a defined value. We hypothesised that such pre-emptive therapy should occur earlier than the standard 3000 genomes/ml (2520 IU/ml) when a seropositive donor transmitted virus to a seronegative recipient (D+R-) following solid organ transplantation (SOT). METHODS: Our local protocol was changed so that D+R- SOT patients commenced valganciclovir once the viral load exceeded 200 genomes/ml; 168 IU/ml (new protocol). The decision point remained at 3000 genomes/ml (old protocol) for the other two patient subgroups (D+R+, D-R+). Virological outcomes were assessed three years later, when 74 D+R- patients treated under the old protocol could be compared with 67 treated afterwards. The primary outcomes were changes in peak viral load, duration of viraemia and duration of treatment in the D+R- group. The secondary outcome was the proportion of D+R- patients who developed subsequent viraemia episodes. FINDINGS: In the D+R- patients, the median values of peak viral load (30,774 to 11,135 genomes/ml, p<0.0215) were significantly reduced on the new protocol compared to the old, but the duration of viraemia and duration of treatment were not. Early treatment increased subsequent episodes of viraemia from 33/58 (57%) to 36/49 (73%) of patients (p< 0.0743) with a significant increase (p = 0.0072) in those episodes that required treatment (16/58; 27% versus 26/49; 53%). Median peak viral load increased significantly (2,103 to 3,934 genomes/ml, p<0.0249) in the D+R+ but not in the D-R+ patient subgroups. There was no change in duration of viraemia or duration of treatment for any patient subgroup. INTERPRETATION: Pre-emptive therapy initiated at the first sign of viraemia post-transplant significantly reduced the peak viral load but increased later episodes of viraemia, consistent with the hypothesis of reduced antigenic stimulation of the immune system

Homocitrullination of lysine residues mediated by myeloid derived suppressor cells in the tumour environment is a target for cancer immunotherapy

Background: Homocitrullination is the post translational modification of lysine that is recognized by T cells. Methods: This study identified homocitrullinated peptides from aldolase, enolase, cytokeratin and Bip and used HLA transgenic mice to assess immunogenicity by ELISpot assay. Vaccine efficacy was assessed in tumour therapy studies using HLA matched B16 melanoma expressing constitutive or IFNγ inducible MHC-II as represented by most human tumours. To determine the mechanism behind the therapy, immune cell infiltrates were analysed using flow cytometry and therapy studies in the presence of MPO inhibitor and T cell depletion performed. We assessed the T cell repertoire to homocitrullinated peptides in cancer patients and healthy donors using flow cytometry. Results: Homocitrulline peptide vaccination stimulated strong CD4 T cell responses and induced significant anti-tumour therapy in an established tumour model. The anti-tumour response was dependent upon CD4 T-cells and the effect was driven mainly via direct tumour recognition, as responses were only observed if the tumours were induced to express MHC-II. In vitro proliferation assays show that healthy donors and cancer patients have an oligoclonal CD4 T-cell repertoire recognizing homocitrullinated peptides. Inhibition of cyanate generation, which mediates homocitrullination, by myeloperoxidase (MPO) inhibition reduced tumour therapy by the vaccine induced T cells (P=0.0018). Analysis of the tumour microenvironment (TME) suggested that myeloid-derived suppressor cells (MDSCs) were a potential source of MPO. The selected B16 melanoma model showed MDSC infiltration. and was appropriate to see if the homocitrulline vaccine could overcome the immunosuppression associated with MDSCs. The vaccine was very effective (90% survival) as the induced CD4 T cells directly targeted the homocitrullinated tumour and likely reversed the immunosuppressive environment. Conclusion: We propose that MPO, potentially produced by MDSCs, catalyses the build-up of cyanate in the TME which diffuses into tumour cells causing homocitrullination of cytoplasmic proteins which are degraded and, in the presence of IFNγ, presented by MHC-II for direct CD4 T-cell recognition. Homocitrullinated proteins are a new target for cancer vaccines and may be particularly effective against tumours containing high levels of MPO expressing MDSCs

Correction: Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy

An affiliation for the last author is missing. Vincent C. Emery is also affiliated with Department of Microbial and Cellular Sciences, University of Surrey, Guildford, Surrey, United Kingdom

Hypoglycaemia in severe malaria, clinical associations and relationship to quinine dosage

<p>Abstract</p> <p>Background</p> <p>Hypoglycaemia is an independent risk factor for death in severe malaria and a recognized adverse treatment effect of parenteral quinine. In 2006 our hospital changed quinine treatment policy from 15 mg/kg loading (plus 10 mg/kg 12-hourly) to 20 mg/kg loading (plus 10 mg/kg 8-hourly) to comply with new WHO guidelines. This presented us with the opportunity to examine whether there was any dose relationship of quinine and hypoglycaemia occurrence.</p> <p>Methods</p> <p>Retrospective case notes review of all children admitted to hospital with severe falciparum malaria between April 2002 - July 2009, before and after the introduction of the new WHO quinine regimen. Four-hourly bedside glucose levels were measured until intravenous quinine was discontinued. Clinical events immediately preceding or concurrent with each episode of hypoglycaemia (glucose < = 3.0 mmol/l) were recorded.</p> <p>Results</p> <p>954 children received the old quinine regime and 283 received the new regime. We found no evidence of an increased prevalence of hypoglycaemia (< = 3.0 mmol/L) on the new regime compared to former (15% vs. 15%); similar findings were noted for profound hypoglycaemia (< 2.2 mmols/L) 8% v 5%, P = 0.07. Episodes were co-incident with disease severity markers: coma (57%), circulatory failure (38%) and respiratory distress (21%) but less commonly with seizures (10%). Disruption of maintenance fluids and/or blood transfusion concurred with 42% of the hypoglycaemia episodes. Post admission hypoglycaemia increased odds of fatal outcome (24%) compared to euglycaemic counterparts (8%), odds ratio = 3.45 (95% confidence interval = 2.30-5.16) P < 0.01.</p> <p>Conclusion</p> <p>There was no evidence to indicate a dose relationship between quinine and occurrence of hypoglycaemia. Hypoglycaemia concurred with severity features, disruption of glucose infusion and transfusion. Careful glucose monitoring should be targeted to these complications where resources are limited.</p

Simultaneous determination of V, Ni, Ga and Fe in fuel fly ash using solid sampling high resolution continuum source graphite furnace atomic absorption spectrometry

A green and simple method has been proposed in this work for the simultaneous determination of V, Ni, Ga and Fe in fuel ash samples by solid sampling high resolution continuum source graphite furnace atomic absorption spectrometry (SS HR CS GFAAS). The application of fast programs in combination with direct solid sampling allows eliminating pretreatment steps, involving minimal manipulation of sample. Iridium treated platforms were applied throughout the present study, enabling the use of aqueous standards for calibration. Correlation coefficients for the calibration curves were typically better than 0.9931. The concentrations found in the fuel ash samples analyzed ranged from 0.66 to 4.2 % for V, 0.23 to 0.7 % for Ni, 0 to 5.4 mg/Kg for Ga and 0.10 to 0.60 % for Fe. Precision (%RSD) were 5.2, 10.0, 20.0 and 9.8% for V, Ni, Ga and Fe, respectively, obtained as the average of the %RSD of six replicates of each fuel ash sample. The optimum conditions established were applied to the determination of the target analytes in fuel ash samples. In order to test the accuracy and applicability of the proposed method in the analysis of samples, five ash samples from the combustion of fuel in power stations, were analysed. The method accuracy was evaluated by comparing the results obtained using the proposed method with the results obtained by ICP OES previous acid digestion. The results showed good agreement between them