Modelling and analysis of turbulent datasets using Auto Regressive Moving Average processes

International audienceWe introduce a novel way to extract information from turbulent datasets by applying an Auto Regressive Moving Average (ARMA) statistical analysis. Such analysis goes well beyond the analysis of the mean flow and of the fluctuations and links the behavior of the recorded time series to a discrete version of a stochastic differential equation which is able to describe the correlation structure in the dataset. We introduce a new index ϒ that measures the difference between the resulting analysis and the Obukhov model of turbulence, the simplest stochastic model reproducing both Richardson law and the Kolmogorov spectrum. We test the method on datasets measured in a von Kármán swirling flow experiment. We found that the ARMA analysis is well correlated with spatial structures of the flow, and can discriminate between two different flows with comparable mean velocities, obtained by changing the forcing. Moreover, we show that the ϒ is highest in regions where shear layer vortices are present, thereby establishing a link between deviations from the Kolmogorov model and coherent structures. These deviations are consistent with the ones observed by computing the Hurst exponents for the same time series. We show that some salient features of the analysis are preserved when considering global instead of local observables. Finally, we analyze flow configurations with multistability features where the ARMA technique is efficient in discriminating different stability branches of the system

Reduction in oxidatively generated DNA damage following smoking cessation

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking is a known cause of cancer, and cancer may be in part due to effects of oxidative stress. However, whether smoking cessation reverses oxidatively induced DNA damage unclear. The current study sought to examine the extent to which three DNA lesions showed significant reductions after participants quit smoking.</p> <p>Methods</p> <p>Participants (n = 19) in this study were recruited from an ongoing 16-week smoking cessation clinical trial and provided blood samples from which leukocyte DNA was extracted and assessed for 3 DNA lesions (thymine glycol modification [d(T^gpA)]; formamide breakdown of pyrimidine bases [d(T^gpA)]; 8-oxo-7,8-dihydroguanine [d(G^h)]) via liquid chromatography tandem mass spectrometry (LC-MS/MS). Change in lesions over time was assessed using generalized estimating equations, controlling for gender, age, and treatment condition.</p> <p>Results</p> <p>Overall time effects for the d(T^gpA) (χ²(3) = 8.068, p < 0.045), d(P^fpA) (χ²(3) = 8.477, p < 0.037), and d(G^h) (χ²(3) = 37.599, p < 0.001) lesions were seen, indicating levels of each decreased significantly after CO-confirmed smoking cessation. The d(T^gpA) and d(P^fpA) lesions show relatively greater rebound at Week 16 compared to the d(G^h) lesion (88% of baseline for d(T^gpA), 64% of baseline for d(P^fpA), vs 46% of baseline for d(G^h)).</p> <p>Conclusions</p> <p>Overall, results from this analysis suggest that cigarette smoking contributes to oxidatively induced DNA damage, and that smoking cessation appears to reduce levels of specific damage markers between 30-50 percent in the short term. Future research may shed light on the broader array of oxidative damage influenced by smoking and over longer durations of abstinence, to provide further insights into mechanisms underlying carcinogenesis.</p

Improvement in RNA extraction from S. cerevisie by optimization in the autolysis and NH3 hydrolysis

The optimization of autolysis of Saccharomyces cerevisiae from brewery was studied aiming at the maximum ribonucleic acid extraction and yeast extract production. The best conditions for yeast autolysis was 55.2ºC, pH= 5.1 and 9.8% NaCl for 24h of processing, without the NH3 use. In these conditions, the RNA yield was 89.7%, resulting in 51.3% of dehydrated yeast extract with 57.9% protein. The use of 12.2% NH3 at 60ºC after autolysis (8h) and plasmolysis (8h) was not viable due to the reduction in the RNA yield from 89.7to78.4%. On the other hand, the thermal shock at 60ºC for 15 minutes prior to autolysis provided an increase in the yield from 89.7 to 91.4%. The autolysis, including NaCl plasmolysis in the optimized conditions was efficient, economic and with short time, thus usable for industrial purpose to obtain more valuable products such as yeast extract enriched in RNA and/or protein, for different applications

Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation

Objectives: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. Methods: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1&nbsp;year. We analysed outcomes of viral suppression (&lt;&nbsp;200&nbsp;HIV-1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. Results: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR)&nbsp;0.84; 95% credibility interval (CrI) 0.71–0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n&nbsp;=&nbsp;184; HR&nbsp;0.94; 95% CrI 0.73–1.15) or FTC (n&nbsp;=&nbsp;454; HR&nbsp;0.99; 95% CrI 0.80–1.19) amongst those on tenofovir-containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n&nbsp;=&nbsp;481; HR 0.71; 95% CrI 0.54–0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR&nbsp;0.92; 95% CrI 0.64–1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34–1.11). Conclusions: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A short introduction to the literature of the Old Testament /

Includes bibliographical references and index.Mode of access: Internet