Developement of real time diagnostics and feedback algorithms for JET in view of the next step

Real time control of many plasma parameters will be an essential aspect in the development of reliable high performance operation of Next Step Tokamaks. The main prerequisites for any feedback scheme are the precise real-time determination of the quantities to be controlled, requiring top quality and highly reliable diagnostics, and the availability of robust control algorithms. A new set of real time diagnostics was recently implemented on JET to prove the feasibility of determining, with high accuracy and time resolution, the most important plasma quantities. With regard to feedback algorithms, new model–based controllers were developed to allow a more robust control of several plasma parameters. Both diagnostics and algorithms were successfully used in several experiments, ranging from H-mode plasmas to configuration with ITBs. Since elaboration of computationally heavy measurements is often required, significant attention was devoted to non-algorithmic methods like Digital or Cellular Neural/Nonlinear Networks. The real time hardware and software adopted architectures are also described with particular attention to their relevance to ITER.Comment: 12th International Congress on Plasma Physics, 25-29 October 2004, Nice (France

Style modification in breast and Colorectal Cancer Patients: results of a pilot study Long-Survivors

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Applications of lignin in the agri-food industry

Of late, valorization of agri-food industrial by-products and their sustainable utilization is gaining much contemplation world-over. Globally, 'Zero Waste Concept' is promoted with main emphasis laid towards generation of minimal wastes and maximal utilization of plantbased agri-food raw materials. One of the wastes/by-products in the agri-food industry are the lignin, which occurs as lignocellulosic biomass. This biomass is deliberated to be an environmental pollutant as they offer resistance to natural biodegradation. Safe disposal of this biomass is often considered a major challenge, especially in low-income countries. Hence, the application of modern technologies to effectively reduce these types of wastes and maximize their potential use/applications is vital in the present day scenario. Nevertheless, in some of the high-income countries, attempts have been made to efficiently utilize lignin as a source of fuel, as a raw material in the paper industry, as a filler material in biopolymer based packaging and for producing bioethanol. However, as of today, agri-food industrial applications remains significantly underexplored. Chemically, lignin is heterogeneous, bio-polymeric, polyphenolic compound, which is present naturally in plants, providing mechanical strength and rigidity. Reports are available wherein purified lignin is established to possess therapeutic values; and are rich in antioxidant, anti-microbial, anti-carcinogenic, antidiabetic properties, etc. This chapter is divided into four sub-categories focusing on various technological aspects related to isolation and characterization of lignin; established uses of lignin; proved bioactivities and therapeutic potentials of lignin, and finally on identifying the existing research gaps followed by future recommendations for potential use from agri-food industrial wastes.Theme of this chapter is based on our ongoing project- Valortech, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 810630

A systematic review on the excess health risk of antibiotic-resistant bloodstream infections for six key pathogens in Europe

Background: Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined. Objectives: We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe. Methods: A systematic review and meta-analysis. Data sources: MEDLINE, Embase, and grey literature for the period January 1990 to May 2022. Study eligibility criteria: Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries. Participants: Paediatric and adult patients diagnosed with drug-resistant BSI. Interventions: Not applicable. Assessment of risk of bias: An adapted version of the Joanna-Briggs Institute assessment tool. Methods of data synthesis: Random-effect models were used to pool pathogen-specific burden estimates. Results: We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03–1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62–7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92–18.09] and OR 6.18 [95% CI 2.10–18.17], respectively). Conclusions: Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions

Adjuvant chemotherapy in colorectal cancer patients with microsatellite instability - Response

Inresponse: The major criticism raised by Watanabe in his letter about our recently published article (1) concerns the number of patients with stage II and III MSI-Hcolorectal cancer (CRC) who received chemotherapy, that ‘‘should be around 20 at most’’ and thus ‘‘seems too small to draw any conclusions.’’ The assumption of Watanabe on the small number of patients in our study is based on his interpretation that among those 65 MSI-Hwho received chemotherapy, 31 were in stage IV. This assumption is not correct. In fact, we considered as patients receiving adjuvant chemotherapy only those who underwent surgical intervention with curative intent (i.e., radical surgery), thus excluding most of stage IV patients who received only palliative chemotherapy. We apologize for the fact that this explanation was not present in the text leading to the misinterpretation of the data. On this basis, among the 65 MSI-Hpatients considered as treated with adjuvant chemotherapy, only 2 were in stage IV whereas 25 were in stage II and the remaining 38 were in stage III, which is almost double of what was hypothesized. Furthermore, Watanabe states that the results of our study ‘‘could potentially bias the significance of MSI-Has predictor of survival in adjuvant-treated colon cancer patients’’ as shown by the results of his study (2), which compared the survival of MSI-Hand MSS patients in stage II and III who received chemotherapy. We think that our results are not completely comparable with those of Watanabe, mainly for the reason that our study had a different design. In his work, Watanabe compared, among patients who received chemotherapy, those affected by MSI-HCRC versus those with stable tumors and found a survival advantage in the first group; this study design could not clearly establish whether this prognostic advantage is conferred by the better sensitivity of MSI-HCRC to chemotherapeutic agents or is due to the presence of instability by itself. On the contrary, our study was designed to investigate the sensitivity of MSI-HCRC to chemotherapy. For this reason, we compared among MSI-HCRC patients the outcome of those who underwent 5-fluorouracil-based chemotherapy versus those who were not treated. The results showed that chemotherapy did not confer any survival advantage in MSI-HCRC patients, confirming the report of another study with larger sample size (3). In addition, the results of multivariate analysis in stage II and III CRC cases showed the presence of MSI-H as an independent prognostic factor: this means that even in our study, in accordance with Watanabe’s study, among patients who received chemotherapy, MSI-Hpatients have a better outcome than MSS patients. Finally, another difference between the two studies involved the definition of MSI. To define MSI, in our study, we used the reference marker panel, as established in Bethesda guidelines. Watanabe used eight dinucleotide and two polyadenine markers in most cases, or two mononucleotide markers in those cases without normal DNA available. This could have important implications leading to heterogeneity in the population defined as MSI in the two investigations