Optimising the balance of acute and intermediate care capacity for the complex discharge pathway: Computer modelling study during COVID-19 recovery in England.

OBJECTIVES: While there has been significant research on the pressures facing acute hospitals during the COVID-19 pandemic, there has been less interest in downstream community services which have also been challenged in meeting demand. This study aimed to estimate the theoretical cost-optimal capacity requirement for 'step down' intermediate care services within a major healthcare system in England, at a time when considerable uncertainty remained regarding vaccination uptake and the easing of societal restrictions. METHODS: Demand for intermediate care was projected using an epidemiological model (for COVID-19 demand) and regressing upon public mobility (for non-COVID-19 demand). These were inputted to a computer simulation model of patient flow from acute discharge readiness to bedded and home-based Discharge to Assess (D2A) intermediate care services. Cost-optimal capacity was defined as that which yielded the lowest total cost of intermediate care provision and corresponding acute discharge delays. RESULTS: Increased intermediate care capacity is likely to bring about lower system-level costs, with the additional D2A investment more than offset by substantial reductions in costly acute discharge delays (leading also to improved patient outcome and experience). Results suggest that completely eliminating acute 'bed blocking' is unlikely economical (requiring large amounts of downstream capacity), and that health systems should instead target an appropriate tolerance based upon the specific characteristics of the pathway. CONCLUSIONS: Computer modelling can be a valuable asset for determining optimal capacity allocation along the complex care pathway. With results supporting a Business Case for increased downstream capacity, this study demonstrates how modelling can be applied in practice and provides a blueprint for use alongside the freely-available model code.

Modelling the effect of COVID-19 mass vaccination on acute hospital admissions.

BACKGROUND: Managing high levels of acute COVID-19 bed occupancy can affect the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible impact on future bed pressures remained subject to considerable uncertainty. OBJECTIVE: The aim of this study was to model the effect of vaccination on projections of acute and intensive care bed demand within a 1 million resident healthcare system located in South West England. METHODS: An age-structured epidemiological model of the susceptible-exposed-infectious-recovered type was fitted to local data up to the time of the study, in early March 2021. Model parameters and vaccination scenarios were calibrated through a system-wide multidisciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists and academics. Scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021. RESULTS: Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert the third wave in autumn 2021 but would produce a median peak bed requirement ∼6% (IQR: 1-24%) of that experienced during the second wave (January 2021). A 2-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11-146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns), then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19%, respectively, an amount which would seriously pressure hospital capacity. CONCLUSION: Modelling influenced decision-making among senior managers in setting COVID-19 bed capacity levels, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.

Mem-fractive properties of mushrooms.

Memristors close the loop forI-Vcharacteristics of the traditional, passive, semi-conductor devices. A memristor is a physical realisation of the material implication and thus is a universal logical element. Memristors are getting particular interest in the field of bioelectronics. Electrical properties of living substrates are not binary and there is nearly a continuous transitions from being non-memristive to mem-fractive (exhibiting a combination of passive memory) to ideally memristive. In laboratory experiments we show that living oyster mushroomsPleurotus ostreatusexhibit mem-fractive properties. We offer a piece-wise polynomial approximation of theI-Vbehaviour of the oyster mushrooms. We also report spiking activity, oscillations in conduced current of the oyster mushrooms.

Projecting the effect of easing societal restrictions on non-COVID-19 emergency demand in the UK: Statistical inference using public mobility data.

While it is well established that societal restrictions have been effective in reducing COVID-19 emergency demand, evidence also suggests an impact upon emergency demand not directly related to COVID-19 infection. Hospital planning may benefit from a greater understanding of this association and the ability to reliably forecast future levels of non-COVID-19 demand. Activity data for Accident and Emergency (A&E) attendances and emergency admissions were sourced for all hospitals within the Bristol, North Somerset and South Gloucestershire healthcare system. These were regressed upon publicly available mobility data obtained from Google's Community Mobility Reports for the local area. Seasonal trends were controlled for using time series decomposition. The models were used to predict non-COVID-19 emergency demand under the UK Government's plan to sequentially lift all restrictions by 21 June 2021, in addition to three alternative hypothetical relaxation strategies. Rates of public mobility within the local area were shown to account for 77% and 65% of the variance in non-COVID-19 related A&E attendances and emergency admissions respectively. Modelling supports an increase in emergency demand in line with the level and timing of societal restrictions, with significant increases to be expected upon the ending of all legal limits. This study finds that non-COVID-19 emergency demand associates with the level of societal restrictions, with rates of public mobility representing a key determinant. Through predictive modelling, healthcare systems can improve their demand forecasting in effectively managing hospital capacity.

On Boolean gates in fungal colony.

A fungal colony maintains its integrity via flow of cytoplasm along mycelium network. This flow, together with possible coordination of mycelium tips propagation, is controlled by calcium waves and associated waves of electrical potential changes. We propose that these excitation waves can be employed to implement a computation in the mycelium networks. We use FitzHugh-Nagumo model to imitate propagation of excitation in a single colony of Aspergillus niger. Boolean values are encoded by spikes of extracellular potential. We represent binary inputs by electrical impulses on a pair of selected electrodes and we record responses of the colony from sixteen electrodes. We derive sets of two-inputs-on-output logical gates implementable the fungal colony and analyse distributions of the gates.

Anterior thalamic nuclei, but not retrosplenial cortex, lesions abolish latent inhibition in rats.

The present study examined the effects of excitotoxic lesions in 2 closely related structures, the anterior thalamic nuclei and the retrosplenial cortex, on latent inhibition. Latent inhibition occurs when nonreinforced preexposure to a stimulus retards the subsequent acquisition of conditioned responding to that stimulus. Latent inhibition was assessed in a within-subject procedure with auditory stimuli and food reinforcement. As expected, sham-operated animals were slower to acquire conditioned responding to a stimulus that had previously been experienced without consequence, relative to a non-preexposed stimulus. This latent inhibition effect was absent in rats with excitotoxic lesions in the anterior thalamic nuclei, as these animals conditioned to both stimuli at equivalent rates. The retrosplenial lesions appeared to spare latent inhibition, as these animals displayed a robust stimulus preexposure effect. The demonstration here that anterior thalamic nuclei lesions abolish latent inhibition is consistent with emerging evidence of the importance of these thalamic nuclei for attentional control. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Lesions of retrosplenial cortex spare immediate-early gene activity in related limbic regions in the rat.

The retrosplenial cortex forms part of a network of cortical and subcortical structures that have particular importance for spatial learning and navigation in rodents. This study examined how retrosplenial lesions affect activity in this network by visualising the expression of the immediate-early genes c-fos and zif268 after exposure to a novel location. Groups of rats with extensive cytotoxic lesions (areas 29 and 30) and rats with lesions largely confined to area 30 (dysgranular cortex) were compared with their respective control animals for levels of c-fos expression measured by immunohistochemistry. These cortical lesions had very limited effects on distal c-fos activity. Evidence of a restricted reduction in c-fos activity was seen in the septal dentate gyrus (superior blade) but not in other hippocampal and parahippocampal subareas, nor in the anterior cingulate and prelimbic cortices. Related studies examined zif268 activity in those cases with combined area 29 and 30 lesions. The only clear evidence for reduced zif268 activity following retrosplenial cell loss came from the septal CA3 area. The confined impact of retrosplenial tissue loss is notable as, by the same immediate-early gene measures, retrosplenial cortex is itself highly sensitive to damage in related limbic areas, showing a marked c-fos and zif268 hypoactivity across all of its subareas. This asymmetry in covert pathology may help to explain the apparent disparity between the severity of learning deficits after retrosplenial cortex lesions and after lesions in either the hippocampus or the anterior thalamic nuclei.

The rat retrosplenial cortex as a link for frontal functions: A lesion analysis.

Cohorts of rats with excitotoxic retrosplenial cortex lesions were tested on four behavioural tasks sensitive to dysfunctions in prelimbic cortex, anterior cingulate cortex, or both. In this way the study tested whether retrosplenial cortex has nonspatial functions that reflect its anatomical interactions with these frontal cortical areas. In Experiment 1, retrosplenial cortex lesions had no apparent effect on a set-shifting digging task that taxed intradimensional and extradimensional attention, as well as reversal learning. Likewise, retrosplenial cortex lesions did not impair a strategy shift task in an automated chamber, which involved switching from visual-based to response-based discriminations and, again, included a reversal (Experiment 2). Indeed, there was evidence that the retrosplenial lesions aided the initial switch to response-based selection. No lesion deficit was found on an automated cost-benefit task that pitted size of reward against effort to achieve that reward (Experiment 3). Finally, while retrosplenial cortex lesions affected matching-to-place task in a T-maze, the profile of deficits differed from that associated with prelimbic cortex damage (Experiment 4). When the task was switched to a nonmatching design, retrosplenial cortex lesions had no apparent effect on performance. The results from the four experiments show that many frontal tasks do not require the retrosplenial cortex, highlighting the specificity of their functional interactions. The results show how retrosplenial cortex lesions spare those learning tasks in which there is no mismatch between the internal and external representations used to guide behavioural choice. In addition, these experiments further highlight the importance of the retrosplenial cortex in solving tasks with a spatial component.

The retrosplenial cortex and object recency memory in the rat.

It has been proposed that the retrosplenial cortex forms part of a 'where/when' information network. The present study focussed on the related issue of whether retrosplenial cortex also contributes to 'what/when' information, by examining object recency memory. In Experiment 1, rats with retrosplenial lesions were found to be impaired at distinguishing the temporal order of objects presented in a continuous series ('Within-Block' condition). The same lesioned rats could, however, distinguish between objects that had been previously presented in one of two discrete blocks ('Between-Block' condition). Experiment 2 used intact rats to map the expression of the immediate-early gene c-fos in retrosplenial cortex following performance of a between-block, recency discrimination. Recency performance correlated positively with levels of c-fos expression in both granular and dysgranular retrosplenial cortex (areas 29 and 30). Expression of c-fos in the granular retrosplenial cortex also correlated with prelimbic cortex and ventral subiculum c-fos activity, the latter also correlating with recency memory performance. The combined findings from both experiments reveal an involvement of the retrosplenial cortex in temporal order memory, which includes both between-block and within-block problems. The current findings also suggest that the rat retrosplenial cortex comprises one of a group of closely interlinked regions that enable recency memory, including the hippocampal formation, medial diencephalon and medial frontal cortex. In view of the well-established importance of the retrosplenial cortex for spatial learning, the findings support the notion that, with its frontal and hippocampal connections, retrosplenial cortex has a key role for both what/when and where/when information.

Asymmetric cross-hemispheric connections link the rat anterior thalamic nuclei with the cortex and hippocampal formation.

Dense reciprocal connections link the rat anterior thalamic nuclei with the prelimbic, anterior cingulate and retrosplenial cortices, as well as with the subiculum and postsubiculum. The present study compared the ipsilateral thalamic-cortical connections with the corresponding crossed, contralateral connections between these same sets of regions. All efferents from the anteromedial thalamic nucleus to the cortex, as well as those to the subiculum, remained ipsilateral. In contrast, all of these target sites provided reciprocal, bilateral projections to the anteromedial nucleus. While the anteroventral thalamic nucleus often shared this same asymmetric pattern of cortical connections, it received relatively fewer crossed inputs than the anteromedial nucleus. This difference was most marked for the anterior cingulate projections, as those to the anteroventral nucleus remained almost entirely ipsilateral. Unlike the anteromedial nucleus, the anteroventral nucleus also appeared to provide a restricted, crossed projection to the contralateral retrosplenial cortex. Meanwhile, the closely related laterodorsal thalamic nucleus had almost exclusively ipsilateral efferent and afferent cortical connections. Likewise, within the hippocampus, the postsubiculum seemingly had only ipsilateral efferent and afferent connections with the anterior thalamic and laterodorsal nuclei. While the bilateral cortical projections to the anterior thalamic nuclei originated predominantly from layer VI, the accompanying sparse projections from layer V largely gave rise to ipsilateral thalamic inputs. In testing a potentially unifying principle of anterior thalamic - cortical interactions, a slightly more individual pattern emerged that reinforces other evidence of functional differences within the anterior thalamic and also helps to explain the consequences of unilateral interventions involving these nuclei.

What does spatial alternation tell us about retrosplenial cortex function?

The retrosplenial cortex supports navigation, but there are good reasons to suppose that the retrosplenial cortex has a very different role in spatial memory from that of the hippocampus and anterior thalamic nuclei. For example, retrosplenial lesions appear to have little or no effect on standard tests of spatial alternation. To examine these differences, the current study sought to determine whether the retrosplenial cortex is important for just one spatial cue type (e.g., allocentric, directional or intra-maze cues) or whether the retrosplenial cortex helps the animal switch between competing spatial strategies or competing cue types. Using T-maze alternation, retrosplenial lesion rats were challenged with situations in which the available spatial information between the sample and test phases was changed, so taxing the interaction between different cue types. Clear lesion deficits emerged when intra- and extra-maze cues were placed in conflict (by rotating the maze between the sample and choice phases), or when the animals were tested in the dark in a double-maze. Finally, temporary inactivation of the retrosplenial cortex by muscimol infusions resulted in a striking deficit on standard T-maze alternation, indicating that, over time, other sites may be able to compensate for the loss of the retrosplenial cortex. This pattern of results is consistent with the impoverished use of both allocentric and directional information, exacerbated by an impaired ability to switch between different cue types.