Stable modulation of neuronal oscillations produced through brain-machine equilibrium

Brain stimulation is predominantly delivered independent of ongoing activity, whereas closed-loop systems can modify activity through interaction. They have the unrealised potential to continuously bind external stimulation to specific dynamics of a neural circuit. Such manipulations are particularly suited to rhythmic activities, where neuronal activity is organised in oscillatory cycles. Here, we developed a fast algorithm that responds on a cycle-by-cycle basis to stimulate basal ganglia nuclei at predetermined phases of successive cortical beta cycles in parkinsonian rats. Using this approach, we demonstrate a stable brain-machine interaction. An equilibrium emerged between the modified brain signal and feedback-dependent stimulation pattern, which led to sustained amplification or suppression of the oscillation. Sustained beta amplification slowed movement speed by altering the mode of locomotion. Integrating an external stimulus with network activity in this way could be used to correct maladaptive activities and to define the role of oscillations in fundamental brain functions.

Fast adaptation of cooperative channels engenders Hopf bifurcations in auditory hair cells

Since the pioneering work of Thomas Gold published in 1948, it has been known that we owe our sensitive sense of hearing to a process in the inner ear that can amplify incident sounds on a cycle-by-cycle basis. Termed the active process, it uses energy to counteract the viscous dissipation associated with sound-evoked vibrations of the ear's mechanotransduction apparatus. Despite its importance, the mechanism of the active process and the proximate source of energy that powers it have remained elusive—especially at the high frequencies characteristic of mammalian hearing. This is partly due to our insufficient understanding of the mechanotransduction process in hair cells, the sensory receptors and amplifiers of the inner ear. It has previously been proposed that a cyclical binding of Ca2+ ions to individual mechanotransduction channels could power the active process. That model, however, relied on tailored reaction rates that structurally forced the direction of the cycle. Here, we ground our study on our previous model of hair-cell mechanotransduction, which relied on the cooperative gating of pairs of channels, and incorporate into it the cyclical binding of Ca2+ ions. With a single binding site per channel and reaction rates drawn from thermodynamic principles, our model shows that hair cells behave as nonlinear oscillators that exhibit Hopf bifurcations, dynamical instabilities long understood to be signatures of the active process. Using realistic parameter values, we find bifurcations at frequencies in the kilohertz range with physiological Ca2+ concentrations. In contrast to the myosin-based mechanism, responsible for low-frequency relaxation oscillations in the vestibular hair cells of amphibians, the current model relies on the electrochemical gradient of Ca2+ as the only energy source for the active process and on the relative motion of cooperative channels within the stereociliary membrane as the single mechanical driver. Equipped with these two mechanisms, a hair bundle proves capable of operating at frequencies in the kilohertz range, characteristic of mammalian hearing.

The structure and behaviour of hierarchical infrastructure networks

Critical services depend on infrastructure networks for their operation and any disruption to these networks can have significant impacts on society, the economy, and quality of life. Such networks can be characterised as graphs which can be used to understand their structural properties, and the effect on their behaviour and robustness to hazards. Using a suite of graphs and critical infrastructure networks, this study aims to show that networks which exhibit a hierarchical structure are more likely to be less robust comparatively to non-hierarchical networks when exposed to failures, including those which supply critical services. This study investigates the properties of a hierarchical structure through identifying a set of key characteristics from an ensemble of graph models which are then used in a comparative analysis against a suite of spatial critical infrastructure networks. A failure model is implemented and applied to understand the implications of hierarchical structures in real world networks for their robustness to perturbations. The study concludes that a set of three graph metrics, cycle basis, maximum betweenness centrality and assortativity coefficient, can be used to identify the extent of a hierarchy in graphs, where a lack of robustness is linked to the hierarchical structure, a feature exhibited in both graph models and infrastructure networks.

Economic burden of enhanced practices of duodenoscopes reprocessing and surveillance: balancing risk and cost containment

Background and study aims Recent outbreaks attributed to contaminated duodenoscopes have led to the development of enhanced surveillance and reprocessing techniques (enhanced-SRT) aimed at minimizing cross-contamination. Common enhanced-SRT include double high-level disinfection (HLD), ethylene oxide (EtO) gas sterilization, and culture-based monitoring of reprocessed scopes. Adoption of these methods adds to the operational costs and we aimed to assess its economic impact to an institution. Methods We compared the estimated costs of three enhanced-SRT versus single-HLD using data from two institutions. We examined the cost of capital measured as scope inventory and frequency of scope use per unit time, the constituent reprocessing costs required on a per-cycle basis, and labor & staffing needs. The economic impact attributable to enhanced-SRT was defined as the difference between the total cost of enhanced-SRT and single HLD. Results Compared to single HLD, adoption of double HLD increased the costs approximately by 47 % ($80 vs $118). Similarly, culture and quarantine and EtO sterilization increased costs by 160 % and 270 %, respectively ($80 vs $208 and $296). Enhanced-SRT introduced significant scope downtime due to prolonged techniques, necessitating a 3.4-fold increase in the number of scopes needed to maintain procedural volume. The additional annual budget required to implement enhanced-SRT approached $406,000 per year in high-volume centers. Conclusions While enhanced-SRT may reduce patient risk of exposure to contaminated duodenoscopes, it significantly increases the cost of performing ERCP. Future innovation should focus on approaches that can ensure patient safety while maintaining the ability to perform ERCP in a cost-effective manner.

A risk-informed decision support tool for the strategic asset management of railway track infrastructure

The provision of safe, efficient, reliable and affordable railway transport requires the railway track infrastructure to be maintained to an appropriate condition. Given the constrained budgets under which the infrastructure is managed, maintenance needs to be predicted in advance of track failure, prioritized and identified risks and uncertainties need to be considered within the decision-making process. This paper describes a risk-informed approach that can be used to economically justify railway track infrastructure conditions by comparing on a life-cycle basis infrastructure maintenance costs, train operating costs, travel time costs, safety, social and environmental impacts. The approach represents a step-change for the railway industry as it will enable economic maintenance standards to be derived which considers the needs of the infrastructure operator, but also those of users, train operating companies and the environment. Further, the risk-informed capability of the tool enables asset managers to deal with uncertainties associated with forecasting costs and the effects of track maintenance, and unavailability of data. The Monte Carlo simulation technique and a Fuzzy reasoning approach are used to address safety data uncertainties through probabilistic risk assessment allied to expert opinion. The approach is illustrated using data from three routes on the UK mainline railway network. The results demonstrate that the approach can be used to support strategic and tactical levels of railway asset management to inform plausible design and maintenance strategies that realise the maximum benefit for the available budget.

P–503 Focus groups with health care professionals, patient advocates and patients to explore how the potential need for multiple cycles is managed during fertility treatment consultations

Study question How is possibility of failure and potential need for multiple cycles discussed with patients during the first or repeat IVF/ICSI treatment consultation? Summary answer Health Care Professionals plan treatment on a cycle-by-cycle basis because it is the normative way to plan treatment, but patients see advantages in multi-cycle planning. What is known already Many patients need more than one round of IVF/ICSI stimulation to achieve their parenthood goals. A recent study has found around 60% of patients to be willing to plan for multiple cycles of treatment. However, it is not clear how patients are informed fully about the high possibility of treatment failure and the subsequent need for multiple cycles during their treatment planning consultations. Study design, size, duration Qualitative focus groups with health care professionals (HCP) patient advocates (April 2020) and patients (July and August 2020, respectively). Patients were eligible if they had had a consultation to start a first/repeat stimulated IVF/ICSI cycle in the eight weeks prior to participation, were aged 18 or older (upper age limit of 42 years for women) and fluent in English. Eligible Health HCPs and patient advocates were those employed at a fertility clinic or charity, respectively. Participants/materials, setting, methods HCP, patient advocate and patient focus group topic guides started with general questions about fertility consultations and progressed to discuss if and how the possibility of treatment failure and need for multiple cycles was introduced and discussed, and then preferences regarding planning IVF/ICSI on a multi-cycle rather than a single cycle basis. Focus groups were recorded, transcribed and analysed using framework analysis which allowed examination of shared, unique and incongruent thematic content across participant groups. Main results and the role of chance Twelve HCPs, 2 patient advocates and 11 patients participated in seven semi-structured online focus group discussions. Framework analysis revealed 52 codes (e.g., possibility of failure tentatively introduced; discussion of multiple cycles dependent on clinical/patient benchmarks) abstracted into 17 higher-level categories (e.g., Failure is a sensitive topic to approach; IVF treatment failure is the norm). Synthesis of categories revealed four themes and one meta theme The meta theme showed planning treatment on a cycle-by-cycle basis was the norm. This meta-theme was supported by four themes: (1) ‘culture of communication’ that dictated benchmarks (e.g., clinic, national live birth rate) and definition of key concepts (’complete’ cycle) that underpinned divergence between clinics; (2) ‘HCP-patient dynamics’ indexing degree of shared decision-making, advance preparation and involvement of partners in planning; (3) ‘tempering optimism’ that described tailoring, balancing and emotion management in giving personal chances of success; and (4) ‘transitioning to multi-cycle planning’ which identified worries of multi-cycle planning (e.g., need to learn from failure). Limitations, reasons for caution The majority of patients were women from private fertility clinics with no previous treatment experience recruited from social media websites, mainly associated with patient support groups. Similarly, the majority of HCPs were women from private fertility clinics. Informative comparisons across treatment stage, gender and funding source were therefore not possible. Wider implications of the findings: HCPs are hesitant towards multi-cycle planning. However, patients show openness, suggesting a cultural shift from the single cycle norm of planning IVF/ICSI may be possible. If adopted by clinics, HCPs patients and fertility organisations, multi-cycle planning could encourage patients to create informed treatment expectations and plans prior to treatment engagemen. Trial registration number MS200059_001

P-503 Focus groups with health care professionals, patient advocates and patients to explore how the potential need for multiple cycles is managed during fertility treatment consultations

Study question How is possibility of failure and potential need for multiple cycles discussed with patients during the first or repeat IVF/ICSI treatment consultation? Summary answer Health Care Professionals plan treatment on a cycle-by-cycle basis because it is the normative way to plan treatment, but patients see advantages in multi-cycle planning What is known already Many patients need more than one round of IVF/ICSI stimulation to achieve their parenthood goals. A recent study has found around 60% of patients to be willing to plan for multiple cycles of treatment. However, it is not clear how patients are informed fully about the high possibility of treatment failure and the subsequent need for multiple cycles during their treatment planning consultations Study design, size, duration Qualitative focus groups with health care professionals (HCP) patient advocates (April 2020) and patients (July and August 2020, respectively). Patients were eligible if they had had a consultation to start a first/repeat stimulated IVF/ICSI cycle in the eight weeks prior to participation, were aged 18 or older (upper age limit of 42 years for women) and fluent in English. Eligible Health HCPs and patient advocates were those employed at a fertility clinic or charity, respectively Participants/materials, setting, methods HCP, patient advocate and patient focus group topic guides started with general questions about fertility consultations and progressed to discuss if and how the possibility of treatment failure and need for multiple cycles was introduced and discussed, and then preferences regarding planning IVF/ICSI on a multi-cycle rather than a single cycle basis. Focus groups were recorded, transcribed and analysed using framework analysis which allowed examination of shared, unique and incongruent thematic content across participant groups Main results and the role of chance Twelve HCPs, 2 patient advocates and 11 patients participated in seven semi-structured online focus group discussions. Framework analysis revealed 52 codes (e.g., possibility of failure tentatively introduced; discussion of multiple cycles dependent on clinical/patient benchmarks) abstracted into 17 higher-level categories (e.g., Failure is a sensitive topic to approach; IVF treatment failure is the norm). Synthesis of categories revealed four themes and one meta theme The meta theme showed planning treatment on a cycle-by-cycle basis was the norm. This meta-theme was supported by four themes: (1) ‘culture of communication’ that dictated benchmarks (e.g., clinic, national live birth rate) and definition of key concepts (‘complete’ cycle) that underpinned divergence between clinics; (2) ‘HCP-patient dynamics’ indexing degree of shared decision-making, advance preparation and involvement of partners in planning; (3) ‘tempering optimism’ that described tailoring, balancing and emotion management in giving personal chances of success; and (4) ‘transitioning to multi-cycle planning’ which identified worries of multi-cycle planning (e.g., need to learn from failure). Limitations, reasons for caution The majority of patients were women from private fertility clinics with no previous treatment experience recruited from social media websites, mainly associated with patient support groups. Similarly, the majority of HCPs were women from private fertility clinics. Informative comparisons across treatment stage, gender and funding source were therefore not possible Wider implications of the findings HCPs are hesitant towards multi-cycle planning. However, patients show openness, suggesting a cultural shift from the single cycle norm of planning IVF/ICSI may be possible. If adopted by clinics, HCPs patients and fertility organisations, multi-cycle planning could encourage patients to create informed treatment expectations and plans prior to treatment engagement Trial registration number MS200059_001

GASOLINE COMPRESSION IGNITION (GCI) ON A LIGHT-DUTY MULTI-CYLINDER ENGINE USING A WIDE RANGE OF FUEL REACTIVITIES & HEAVY FUEL STRATIFICATION

Many research studies have focused on utilizing gasoline in compression ignition engines, known as gasoline compression ignition (GCI). A challenge with GCI operation is maintaining control over the combustion process through the fuel injection strategy, such that the engine can be controlled on a cycle-by-cycle basis. Research studies have investigated a wide variety of injection strategies (i.e., fuel stratification levels) to maintain control over the heat release rate while achieving low temperature combustion (LTC). This work shows that at loads relevant to light-duty engines, partial fuel stratification (PFS) with gasoline provides very little controllability over the timing of combustion. On the contrary, heavy fuel stratification (HFS) provides very linear and pronounced control over the timing of combustion. However, the HFS strategy has challenges achieving LTC operation due to the air handling burdens associated with the high EGR rates that are required to reduce NOx emissions to near zero levels. In this work, a wide variety of gasoline fuel reactivities (octane numbers ranging from <40 to 87) were investigated to understand the engine performance and emissions of HFS-GCI operation on a multi-cylinder light-duty engine. The results indicate that over an EGR sweep at 4 bar BMEP, the gasoline fuels can achieve LTC operation with ultra-low NOx and soot emissions, while conventional diesel combustion (CDC) is unable to simultaneously achieve low NOx and soot. At 10 bar BMEP, all the gasoline fuels were compared to diesel, but using mixing controlled combustion and not LTC.