Optimal consensus control of the Cucker-Smale model

We study the numerical realisation of optimal consensus control laws for agent-based models. For a nonlinear multi-agent system of Cucker-Smale type, consensus control is cast as a dynamic optimisation problem for which we derive first-order necessary optimality conditions. In the case of a smooth penalisation of the control energy, the optimality system is numerically approximated via a gradient-descent method. For sparsity promoting, non-smooth l1-norm control penalisations, the optimal controllers are realised by means of heuristic methods. For an increasing number of agents, we discuss the approximation of the consensus control problem by following a mean-field modelling approach

What do people know about the heritability of sleep?

Study Objectives Twin studies have provided data about the relative weight of genetic and environmental factors on sleep variables over the last few decades. However, heritability is a non-intuitive concept and it is often misunderstood even amongst the scientific community. This study aimed to analyze: (1) understanding of the meaning of heritability of insomnia; (2) the accuracy of estimations of heritability in the general population regarding three sleep traits (sleep duration, sleep quality and insomnia); (3) perceptions of the effectiveness of different treatments for insomnia depending on how the disorder is presented (i.e. having an environmental or genetic etiology) and whether the subject’s estimate of genetic influence on sleep traits impacted beliefs about the effectiveness of different treatments. Methods Participants (N = 3658) completed a survey which included: questions about general genetic knowledge; a specific question about the meaning of heritability; estimates of heritability of three different sleep traits; and the effectiveness of different treatments for insomnia depending on how the etiology of this condition was presented. Results Fewer than 25% of the participants selected the correct description of the heritability of insomnia. Almost half of the sample incorrectly believed that heritability refers to the chance of passing a disorder onto their children. We also found that participants provided different estimates for the effectiveness of different treatments depending on the presumed etiology of the disorder. Conclusion Most people do not have accurate knowledge about the concept of heritability. People’s assumptions about the etiology of a disorder may influence which treatments they consider most effective

Comparison of Antibacterial Activity and Wound Healing in a Superficial Abrasion Mouse Model of Staphylococcus aureus Skin Infection Using Photodynamic Therapy Based on Methylene Blue or Mupirocin or Both

Background: Antibiotic resistance and impaired wound healing are major concerns in S. aureus superficial skin infections, and new therapies are needed. Antimicrobial photodynamic therapy (aPDT) is a new therapeutic approach for infections, but it also improves healing in many wound models. Objective: To compare the antimicrobial activity and the effects on wound healing of aPDT based on Methylene Blue (MB-aPDT) with mupirocin treatment, either alone or in combination, in superficial skin wounds of S. aureus-infected mice. Additionally, to evaluate the clinical, microbiological, and cosmetic effects on wound healing. Materials and Methods: A superficial skin infection model of S. aureus was established in SKH-1 mice. Infected wounds were treated with MB-aPDT, MB-aPDT with a daily topical mupirocin or only with mupirocin. No treatment was carried out in control animals. Daily clinical and microbiological examinations were performed until complete clinical wound healing. Histopathological studies and statistical analysis were performed at the end of the study. Results: MB-aPDT treatment induced the best wound healing compared to mupirocin alone or to mupirocin plus MB-aPDT. Superficial contraction at 24 h and a greater reduction in size at 48 h, quicker detachment of the crust, less scaling, and absence of scars were observed. Histopathological studies correlated with clinical and gross findings. By contrast, mupirocin showed the highest logaritmic reduction of S. aureus. Conclusions: MB-aPDT and mupirocin treatments are effective in a murine superficial skin infection model of S. aureus. One session of MB-aPDT was the best option for clinical wound healing and cosmetic results. The addition of mupirocin to MB-aPDT treatment improved antimicrobial activity; however, it did not enhance wound healing. No synergistic antibacterial effects were detected. © Copyright © 2021 Pérez, Robres, Moreno, Bolea, Verde, Pérez-Laguna, Aspiroz, Gilaberte and Rezusta

Genome-Wide Methylation Profiling in the Thalamus of Scrapie Sheep

Scrapie is a neurodegenerative disorder belonging to the group of transmissible spongiform encephalopathy (TSE). Scrapie occurs in sheep and goats, which are considered good natural animal models of these TSE. Changes in DNA methylation occur in the central nervous system (CNS) of patients suffering from prion-like neurodegenerative diseases, such as Alzheimer''s disease. Nevertheless, potential DNA methylation alterations have not yet been investigated in the CNS of any prion disease model or naturally infected cases, neither in humans nor in animals. Genome-wide DNA methylation patterns were studied in the thalamus obtained from sheep naturally infected with scrapie at a clinical stage (n = 4) and from controls (n = 4) by performing a whole-genome bisulfite sequencing (WGBS) analysis. Ewes carried the scrapie-susceptible ARQ/ARQ PRNP genotype and were sacrificed at a similar age (4–6 years). Although the average genomic methylation levels were similar between the control and the scrapie animals, we identified 8, 907 significant differentially methylated regions (DMRs) and 39 promoters (DMPs). Gene Ontology analysis revealed that hypomethylated DMRs were enriched in genes involved in transmembrane transport and cell adhesion, whereas hypermethylated DMRs were related to intracellular signal transduction genes. Moreover, genes highly expressed in specific types of CNS cells and those previously described to be differentially expressed in scrapie brains contained DMRs. Finally, a quantitative PCR (qPCR) validation indicated differences in the expression of five genes (PCDH19, SNCG, WDR45B, PEX1, and CABIN1) that matched the methylation changes observed in the genomic study. Altogether, these results suggest a potential regulatory role of DNA methylation in prion neuropathology. Copyright © 2022 Hernaiz, Sanz, Sentre, Ranera, Lopez-Pérez, Zaragoza, Badiola, Filali, Bolea, Toivonen and Martín-Burriel

Evaluation of critical parameters in the hollow-fibre system for tuberculosis: A case study of moxifloxacin

AimsThe hollow‐fibre system for tuberculosis (HFS‐TB) is a preclinical model qualified by the European Medicines Agency to underpin the anti‐TB drug development process. It can mimic in vivo pharmacokinetic (PK)–pharmacodynamic (PD) attributes of selected antimicrobials, which could feed into in silico models to inform the design of clinical trials. However, historical data and published protocols are insufficient and omit key information to allow experiments to be reproducible. Therefore, in this work, we aim to optimize and standardize various HFS‐TB operational procedures.MethodsFirst, we characterized bacterial growth dynamics with different types of hollow‐fibre cartridges, Mycobacterium tuberculosis strains and media. Second, we mimicked a moxifloxacin PK profile within hollow‐fibre cartridges, in order to check drug–fibres compatibility. Lastly, we mimicked the moxifloxacin total plasma PK profile in human after once daily oral dose of 400 mg to assess PK–PD after different sampling methods, strains, cartridge size and bacterial adaptation periods before drug infusion into the system.ResultsWe found that final bacterial load inside the HFS‐TB was contingent on the studied variables. Besides, we demonstrated that drug–fibres compatibility tests are critical preliminary HFS‐TB assays, which need to be properly reported. Lastly, we uncovered that the sampling method and bacterial adaptation period before drug infusion significantly impact actual experimental conclusions.ConclusionOur data contribute to the necessary standardization of HFS‐TB experiments, draw attention to multiple aspects of this preclinical model that should be considered when reporting novel results and warn about critical parameters in the HFS‐TB currently overlooked

Origin of Shifts in the Surface Plasmon Resonance Frequencies for Au and Ag Nanoparticles

Origin of shifts in the surface plasmon resonance (SPR) frequency for noble metal (Au, Ag) nanoclusters are discussed in this book chapter. Spill out of electron from the Fermi surface is considered as the origin of red shift. On the other hand, both screening of electrons of the noble metal in porous media and quantum effect of screen surface electron are considered for the observed blue shift in the SPR peak position.Comment: 37 pages, 14 Figures in the submitted book chapter of The Annual Reviews in Plasmonics, edited by Professor Chris D. Geddes. Springer Scinec

Patient Preferences for Lung Cancer Treatment: A Qualitative Study Protocol Among Advanced Lung Cancer Patients

Introduction: Lung cancer is the deadliest and most prevalent cancer worldwide. Lung cancer treatments have different characteristics and are associated with a range of benefits and side effects for patients. Such differences may raise uncertainty among drug developers, regulators, payers, and clinicians regarding the value of these treatment effects to patients. The value of conducting patient preference studies (using qualitative and/or quantitative methods) for benefits and side effects of different treatment options has been recognized by healthcare stakeholders, such as drug developers, regulators, health technology assessment bodies, and clinicians. However, evidence-based guidelines on how and when to conduct and use these studies in drug decision-making are lacking. As part of the Innovative Medicines Initiative PREFER project, we developed a protocol for a qualitative study that aims to understand which treatment characteristics are most important to lung cancer patients and to develop attributes and levels for inclusion in a subsequent quantitative preference survey. Methods: The study protocol specifies a four-phased approach: (i) a scoping literature review of published literature, (ii) four focus group discussions with stage III and IV Non-Small Cell Lung Cancer patients, (iii) two nominal group discussions with stage III and IV Non-Small Cell Lung Cancer patients, and (iv) multi-stakeholder discussions involving clinicians and preference experts. Discussion: This protocol outlines methodological and practical steps as to how qualitative research can be applied to identify and develop attributes and levels for inclusion in patient preference studies aiming to inform decisions across the drug life cycle. The results of this study are intended to inform a subsequent quantitative preference survey that assesses patient trade-offs regarding lung cancer treatment options. This protocol may assist researchers, drug developers, and decision-makers in designing qualitative studies to understand which treatment aspects are most valued by patients in drug development, regulation, and reimbursement

Patient Preferences for Lung Cancer Treatments: A Study Protocol for a Preference Survey Using Discrete Choice Experiment and Swing Weighting

Background: Advanced treatment options for non-small cell lung cancer (NSCLC) consist of immunotherapy, chemotherapy, or a combination of both. Decisions surrounding NSCLC can be considered as preference-sensitive because multiple treatments exist that vary in terms of mode of administration, treatment schedules, and benefit–risk profiles. As part of the IMI PREFER project, we developed a protocol for an online preference survey for NSCLC patients exploring differences in preferences according to patient characteristics (preference heterogeneity). Moreover, this study will evaluate and compare the use of two different preference elicitation methods, the discrete choice experiment (DCE) and the swing weighting (SW) task. Finally, the study explores how demographic (i.e., age, gender, and educational level) and clinical (i.e., cancer stage and line of treatment) information, health literacy, health locus of control, and quality of life may influence or explain patient preferences and the usefulness of a digital interactive tool in providing information on preference elicitation tasks according to patients. Methods: An online survey will be implemented with the aim to recruit 510 NSCLC patients in Belgium and Italy. Participants will be randomized 50:50 to first receive either the DCE or the SW. The survey will also collect information on participants' disease-related status, health locus of control, health literacy, quality of life, and perception of the educational tool. Discussion: This protocol outlines methodological and practical steps to quantitatively elicit and study patient preferences for NSCLC treatment alternatives. Results from this study will increase the understanding of which treatment aspects are most valued by NSCLC patients to inform decision-making in drug development, regulatory approval, and reimbursement. Methodologically, the comparison between the DCE and the SW task will be valuable to gain information on how these preference methods perform against each other in eliciting patient preferences. Overall, this protocol may assist researchers, drug developers, and decision-makers in designing quantitative patient preferences into decision-making along the medical product life cycle

Subsequent mortality in survivors of Ebola virus disease in Guinea: a nationwide retrospective cohort study.

BACKGROUND: A record number of people survived Ebola virus infection in the 2013-16 outbreak in west Africa, and the number of survivors has increased after subsequent outbreaks. A range of post-Ebola sequelae have been reported in survivors, but little is known about subsequent mortality. We aimed to investigate subsequent mortality among people discharged from Ebola treatment units. METHODS: From Dec 8, 2015, Surveillance Active en ceinture, the Guinean national survivors' monitoring programme, attempted to contact and follow-up all survivors of Ebola virus disease who were discharged from Ebola treatment units. Survivors were followed up until Sept 30, 2016, and deaths up to this timepoint were recorded. Verbal autopsies were done to gain information about survivors of Ebola virus disease who subsequently died from their closest family members. We calculated the age-standardised mortality ratio compared with the general Guinean population, and assessed risk factors for mortality using survival analysis and a Cox proportional hazards regression model. FINDINGS: Of the 1270 survivors of Ebola virus disease who were discharged from Ebola treatment units in Guinea, information was retrieved for 1130 (89%). Compared with the general Guinean population, survivors of Ebola virus disease had a more than five-times increased risk of mortality up to Dec 31, 2015 (age-standardised mortality ratio 5·2 [95% CI 4·0-6·8]), a mean of 1 year of follow-up after discharge. Thereafter (ie, from Jan 1-Sept 30, 2016), mortality did not differ between survivors of Ebola virus disease and the general population. (0·6 [95% CI 0·2-1·4]). Overall, 59 deaths were reported, and the cause of death was tentatively attributed to renal failure in 37 cases, mostly on the basis of reported anuria. Longer stays (ie, equal to or longer than the median stay) in Ebola treatment units were associated with an increased risk of late death compared with shorter stays (adjusted hazard ratio 2·62 [95% CI 1·43-4·79]). INTERPRETATION: Mortality was high in people who recovered from Ebola virus disease and were discharged from Ebola treatment units in Guinea. The finding that survivors who were hospitalised for longer during primary infection had an increased risk of death, could help to guide current and future survivors' programmes and in the prioritisation of funds in resource-constrained settings. The role of renal failure in late deaths after recovery from Ebola virus disease should be investigated. FUNDING: WHO, International Medical Corps, and the Guinean Red Cross