A First Step for the Molecular Characterization of Neurological Involvement of Behçet Syndrome: an Italian Pivotal Study

Behçet syndrome (BS) is a vasculitis characterized by several clinical manifestations including the rare neurological involvement (neuro-BS, NBS). The aim of our pivotal study was to investigate the mutational status of several inflammation-related genes in a cohort of Italian patients with and without the neurological involvement (20 NBS vs 40 no-NBS patients). The preliminary in silico single nucleotide polymorphism (SNP) selection and primer design were performed by NCBI Primer-Blast tool. Genomic DNA was isolated and amplified using PCR. PCR amplicons were sequenced and bioinformatically analysed. Twelve tagSNPs were selected and genotyped: ERAP1 rs30187, rs17482078, and rs27044; IL10 rs1800872 and rs1518111, IL12A rs17810546, IL23R rs17375018, IL23R-IL12RB2 rs924080, STAT4 rs7572482, CCR1 rs7616215, KLRC4 rs2617170, and UBAC2 rs3825427. ERAP1 and IL23R SNPs showed statistically significant higher frequencies in NBS group than no-NBS. ERAP1 rs30187 AA was more common in no-NBS patients (20.0% NBS vs 47.5% no-NBS; p < 0.05), while rs17482078 GA frequency was higher in NBS patients (55.0% NBS vs 22.5% no-NBS; p < 0.05, OR: 4.21). IL23R rs17375018 GG was more frequent in NBS group (65.0% NBS vs 40.0% no-NBS; p < 0.05), according to a previous finding. No other statistically significant differences were found. In conclusion, ERAP1 and IL23R SNPs were found associated with neurological involvement of BS. Additional and larger analyses were required to verify our preliminary findings

A Novel Method for Creating a Synthetic L-DOPA Proteome and In Vitro Evidence of Incorporation

Proteinopathies are protein misfolding diseases that have an underlying factor that affects the conformation of proteoforms. A factor hypothesised to play a role in these diseases is the incorporation of non-protein amino acids into proteins, with a key example being the therapeutic drug levodopa. The presence of levodopa as a protein constituent has been explored in several studies, but it has not been examined in a global proteomic manner. This paper provides a proof-of-concept method for enzymatically creating levodopa-containing proteins using the enzyme tyrosinase and provides spectral evidence of in vitro incorporation in addition to the induction of the unfolded protein response due to levodop

On the Use of FOPID Controllers for Maintenance Phase of General Anesthesia

This paper investigates the performance achievable with a fractional-order PID regulator controlling the Depth of Hypnosis (measured via the Bispectral Index Scale) through the administration of propofol during the maintenance phase of total intravenous anesthesia. In particular, two different methodologies were applied to tune the controller: in the first case, genetic algorithms (GAs) were used to minimize the integrated absolute error, while in the second case, the isodamping approach-a method that targets phase margin invariance with respect to the process dc gain-was employed. In both cases, the performance was extensively analyzed and compared with that of a standard PID controller by simulating multiple patients through a Monte Carlo method. The results demonstrate that a fractional-order PID controller can be effectively used to control the Depth of Hypnosis, but the improvement with respect to a standard PID controller is marginal

Terminomics methodologies and the completeness of reductive dimethylation: A meta-analysis of publicly available datasets

© 2019 by the authors. Methods for analyzing the terminal sequences of proteins have been refined over the previous decade; however, few studies have evaluated the quality of the data that have been produced from those methodologies. While performing global N-terminal labelling on bacteria, we observed that the labelling was not complete and investigated whether this was a common occurrence. We assessed the completeness of labelling in a selection of existing, publicly available N-terminomics datasets and empirically determined that amine-based labelling chemistry does not achieve complete labelling and potentially has issues with labelling amine groups at sequence-specific residues. This finding led us to conduct a thorough review of the historical literature that showed that this is not an unexpected finding, with numerous publications reporting incomplete labelling. These findings have implications for the quantitation of N-terminal peptides and the biological interpretations of these data

Event-Based control of depth of hypnosis in anesthesia

Background and Objective: In this paper, we propose the use of an event-based control strategy for the closed-loop control of the depth of hypnosis in anesthesia by using propofol administration and the bispectral index as a controlled variable. Methods: A new event generator with high noise-filtering properties is employed in addition to a PIDPlus controller. The tuning of the parameters is performed off-line by using genetic algorithms by considering a given data set of patients. Results: The effectiveness and robustness of the method is verified in simulation by implementing a Monte Carlo method to address the intra-patient and inter-patient variability. A comparison with a standard PID control structure shows that the event-based control system achieves a reduction of the total variation of the manipulated variable of 93% in the induction phase and of 95% in the maintenance phase. Conclusions: The use of event based automatic control in anesthesia yields a fast induction phase with bounded overshoot and an acceptable disturbance rejection. A comparison with a standard PID control structure shows that the technique effectively mimics the behavior of the anesthesiologist by providing a significant decrement of the total variation of the manipulated variable

A gain-scheduled PID controller for propofol dosing in anesthesia

6siA gain-scheduled proportional-integral-derivative controller is proposed for the closed-loop dosing of propofol in anesthesia (with the bispectral index as a controlled variable). In particular, it is shown that a different tuning of the parameters should be used during the infusion and maintenance phases. Further, the role of the noise filter is investigated.nonenonePadula, F.; Ionescu, C.; Latronico, N.; Paltenghi, M.; Visioli, A.; Vivacqua, G.Padula, Fabrizio; Ionescu, C.; Latronico, Nicola; Paltenghi, M.; Visioli, Antonio; Vivacqua, Giuli

Least Economic Cost Regional Water Supply Planning – Optimising Infrastructure Investments and Demand Management for South East England’s 17.6 Million People

This paper presents a deterministic capacity expansion optimisation model designed for large regional or national water supply systems. The annual model selects, sizes and schedules new options to meet predicted demands at minimum cost over a multi-year time horizon. Options include: supply-side schemes, demand management (water conservation) measures and bulk transfers. The problem is formulated as a mixed integer linear programming (MILP) optimisation model. Capital, operating, carbon, social and environmental costs of proposed discrete schemes are considered. User-defined annual water saving profiles for demand management schemes are allowed. Multiple water demand scenarios are considered simultaneously to ensure the supply–demand balance is preserved across high demand conditions and that variable costs are accurately assessed. A wide range of supplementary constraints are formulated to consider the interdependencies between schemes (pre-requisite, mutual exclusivity, etc.). A two-step optimisation scheme is introduced to prevent the infeasibilities that inevitably appear in real applications. The model was developed for and used by the ‘Water Resources in the South East’ stakeholder group to select which of the 316 available supply schemes (including imports) and 511 demand management options (considering 272 interdependencies) are to be activated to serve the inhabitants of South East of England. Selected schemes are scheduled and sized over a 25 year planning horizon. The model shows demand management options can play a significant role in the region’s water supply and should be considered alongside new supplies and regional transfers. Considering demand management schemes reduced overall total discounted economic costs by 10 % and removed two large reservoirs from the least-cost plan. This case-study optimisation model was built using a generalised data management software platform and solved using a mixed integer linear programme

Developing analytical and academic writing practices through a sustainable blended learning program

Students entering postgraduate coursework degrees transition into content-rich and challenging learning environments, and many are unprepared for the analytical and evaluative skills expected. In the subject ‘Proteomics’, these skills are key for designing an authentic experimental plan, the major assessment. To support our students in developing these critical skills and literacies, we designed, created and embedded three interactive, self-paced H5P online tutorials and two face-to-face writing workshops targeting assignment structure, academic and scientific language, and critical evaluation. Embedding these materials means they are core curriculum and sustainable, supporting a student enhancement rather than a student deficit model (McWilliams & Allen, 2014). In 2020, we adapted our blended design for online delivery by converting the face-to-face workshops into online workshops. Our evaluation showed many students completed the non-assessible online tutorials more than once, suggesting that students used the tutorials to reinforce their understanding of the writing practices presented. Surveys (HREC approved) revealed some students self-reporting increases in confidence in their writing practices, while others remained neutral. Overall, the assignments were better in 2020 than previous years. Our implementation will continue as core content. Ideally, future iterations of the writing workshops will be face-to-face to enable more focussed writing and feedback opportunities. REFERENCES McWilliams, R. & Allen, Q. (2014). Embedding Academic Literacy Skills: Towards a better practice model. Journal of University Teaching & Learning Practice, 11(3), 8

Electrocardiographic markers of structural heart disease and predictors of death in 2332 unselected patients undergoing outpatient Holter recording

To test the hypothesis that the QS interval of ventricular ectopic beats (VEBs) (ventricular ectopic QS interval, VEQSI) would provide a marker for the presence of structural heart disease and a predictor of mortality