What could health technology assessment learn from living clinical practice guidelines?

A "living" approach to clinical practice guidelines is when the identification, appraisal and synthesis of evidence is maintained and repeated at an agreed frequency, with a clear process for when and how new evidence is to be incorporated. The value of a living approach to guidelines was emphasised during the COVID-19 pandemic when health professionals and policymakers needed to make decisions regarding patient care in the context of a nascent but rapidly evolving evidence base. In this perspective, we draw on our recent experience developing Australian and international living guidelines and reflect on the feasibility of applying living guideline methods and processes to a lifecycle approach to health technology assessment (HTA).

A Systematic Review of Pharmacist-Led Antimicrobial Stewardship Programs in Sub-Saharan Africa.

Background: The misuse of antibiotics contributes significantly to antimicrobial resistance (AMR). Higher treatment costs, longer hospital stays, and clinical failure can all result from AMR. According to projections, Africa and Asia will bear the heaviest burden of AMR-related mortalities in the coming years.

Patterns of synchronization in 2D networks of inhibitory neurons.

Neural firing in many inhibitory networks displays synchronous assembly or clustered firing, in which subsets of neurons fire synchronously, and these subsets may vary with different inputs to, or states of, the network. Most prior analytical and computational modeling of such networks has focused on 1D networks or 2D networks with symmetry (often circular symmetry). Here, we consider a 2D discrete network model on a general torus, where neurons are coupled to two or more nearest neighbors in three directions (horizontal, vertical, and diagonal), and allow different coupling strengths in all directions.

Exact mean-field models for spiking neural networks with adaptation.

Networks of spiking neurons with adaption have been shown to be able to reproduce a wide range of neural activities, including the emergent population bursting and spike synchrony that underpin brain disorders and normal function. Exact mean-field models derived from spiking neural networks are extremely valuable, as such models can be used to determine how individual neurons and the network they reside within interact to produce macroscopic network behaviours. In the paper, we derive and analyze a set of exact mean-field equations for the neural network with spike frequency adaptation.

The Impact of Small Time Delays on the Onset of Oscillations and Synchrony in Brain Networks.

The human brain constitutes one of the most advanced networks produced by nature, consisting of billions of neurons communicating with each other. However, this communication is not in real-time, with different communication or time-delays occurring between neurons in different brain areas. Here, we investigate the impacts of these delays by modeling large interacting neural circuits as neural-field systems which model the bulk activity of populations of neurons.

Spatially localized cluster solutions in inhibitory neural networks.

Neurons in the inhibitory network of the striatum display cell assembly firing patterns which recent results suggest may consist of spatially compact neural clusters. Previous computational modeling of striatal neural networks has indicated that non-monotonic, distance-dependent coupling may promote spatially localized cluster firing. Here, we identify conditions for the existence and stability of cluster firing solutions in which clusters consist of spatially adjacent neurons in inhibitory neural networks.

M-current induced Bogdanov-Takens bifurcation and switching of neuron excitability class.

In this work, we consider a general conductance-based neuron model with the inclusion of the acetycholine sensitive, M-current. We study bifurcations in the parameter space consisting of the applied current [Formula: see text], the maximal conductance of the M-current [Formula: see text] and the conductance of the leak current [Formula: see text]. We give precise conditions for the model that ensure the existence of a Bogdanov-Takens (BT) point and show that such a point can occur by varying [Formula: see text] and [Formula: see text].

Stability, bifurcation and phase-locking of time-delayed excitatory-inhibitory neural networks.

We study a model for a network of synaptically coupled, excitable neurons to identify the role of coupling delays in generating different network behaviors. The network consists of two distinct populations, each of which contains one excitatory-inhibitory neuron pair. The two pairs are coupled via delayed synaptic coupling between the excitatory neurons, while each inhibitory neuron is connected only to the corresponding excitatory neuron in the same population.

Patient and Public Involvement Refines the Design of ProtOeus: A Proposed Phase II Trial of Proton Beam Therapy in Oesophageal Cancer.

Background: Neoadjuvant chemoradiotherapy for oesophageal cancer significantly improves overall survival but is associated with severe post-operative complications. Proton beam therapy may reduce these toxicities by sparing normal tissues compared with standard radiotherapy. ProtOeus is a proposed randomised phase II study of neoadjuvant chemoradiotherapy in oesophageal cancer that compares proton beam therapy to standard radiotherapy techniques.

Geometric analysis of synchronization in neuronal networks with global inhibition and coupling delays.

We study synaptically coupled neuronal networks to identify the role of coupling delays in network synchronized behaviour. We consider a network of excitable, relaxation oscillator neurons where two distinct populations, one excitatory and one inhibitory, are coupled with time-delayed synapses. The excitatory population is uncoupled, while the inhibitory population is tightly coupled without time delay.

Outgrowing seizures in Childhood Absence Epilepsy: time delays and bistability.

We formulate a conductance-based model for a 3-neuron motif associated with Childhood Absence Epilepsy (CAE). The motif consists of neurons from the thalamic relay (TC) and reticular nuclei (RT) and the cortex (CT). We focus on a genetic defect common to the mouse homolog of CAE which is associated with loss of GABA receptors on the TC neuron, and the fact that myelination of axons as children age can increase the conduction velocity between neurons.

Chaos in homeostatically regulated neural systems.

Low-dimensional yet rich dynamics often emerge in the brain. Examples include oscillations and chaotic dynamics during sleep, epilepsy, and voluntary movement. However, a general mechanism for the emergence of low dimensional dynamics remains elusive.

Symmetry, Hopf bifurcation, and the emergence of cluster solutions in time delayed neural networks.

We consider the networks of N identical oscillators with time delayed, global circulant coupling, modeled by a system of delay differential equations with Z symmetry. We first study the existence of Hopf bifurcations induced by the coupling time delay and then use symmetric Hopf bifurcation theory to determine how these bifurcations lead to different patterns of symmetric cluster oscillations. We apply our results to a case study: a network of FitzHugh-Nagumo neurons with diffusive coupling.

Mean-field models for heterogeneous networks of two-dimensional integrate and fire neurons.

We analytically derive mean-field models for all-to-all coupled networks of heterogeneous, adapting, two-dimensional integrate and fire neurons. The class of models we consider includes the Izhikevich, adaptive exponential and quartic integrate and fire models. The heterogeneity in the parameters leads to different moment closure assumptions that can be made in the derivation of the mean-field model from the population density equation for the large network.

Sexual health needs and the LGBT community.

Lesbian, gay, bisexual and trans (LGBT) individuals have particular vulnerabilities to sexually transmitted infections and HIV infection. Globally, reasons for this include physiological factors, discrimination and poor understanding of their sexual health needs. In many countries LGBT individuals are not able to exercise fully their rights to health care.

Bifurcations of large networks of two-dimensional integrate and fire neurons.

Recently, a class of two-dimensional integrate and fire models has been used to faithfully model spiking neurons. This class includes the Izhikevich model, the adaptive exponential integrate and fire model, and the quartic integrate and fire model. The bifurcation types for the individual neurons have been thoroughly analyzed by Touboul (SIAM J Appl Math 68(4):1045-1079, 2008).

A closed NPZ model with delayed nutrient recycling.

We consider a closed Nutrient-Phytoplankton-Zooplankton (NPZ) model that allows for a delay in the nutrient recycling. A delay-dependent conservation law allows us to quantify the total biomass in the system. With this, we can investigate how a planktonic ecosystem is affected by the quantity of biomass it contains and by the properties of the delay distribution.

Network bursting using experimentally constrained single compartment CA3 hippocampal neuron models with adaptation.

The hippocampus is a brain structure critical for memory functioning. Its network dynamics include several patterns such as sharp waves that are generated in the CA3 region. To understand how population outputs are generated, models need to consider aspects of network size, cellular and synaptic characteristics and context, which are necessarily 'balanced' in appropriate ways to produce particular outputs.

Webwise.

The Child Accident Prevention Trust (CAPT) is the UK's leading charity working to reduce the number of children and young people killed, disabled or seriously injured in accidents. Its aim is to see children leading active, healthy lives - not 'wrapped in cotton wool'.

The time-delayed inverted pendulum: implications for human balance control.

The inverted pendulum is frequently used as a starting point for discussions of how human balance is maintained during standing and locomotion. Here we examine three experimental paradigms of time-delayed balance control: (1) mechanical inverted time-delayed pendulum, (2) stick balancing at the fingertip, and (3) human postural sway during quiet standing. Measurements of the transfer function (mechanical stick balancing) and the two-point correlation function (Hurst exponent) for the movements of the fingertip (real stick balancing) and the fluctuations in the center of pressure (postural sway) demonstrate that the upright fixed point is unstable in all three paradigms.

Approximating chaotic saddles for delay differential equations.

Chaotic saddles are unstable invariant sets in the phase space of dynamical systems that exhibit transient chaos. They play a key role in mediating transport processes involving scattering and chaotic transients. Here we present evidence (long chaotic transients and fractal basins of attraction) of transient chaos in a "logistic" delay differential equation.

Addressing nursing shortages in sub-Saharan Africa.

The desperate situation of the health workforce in sub-Saharan Africa (SSA) cannot be overstated. This has been a significant and confounding factor in the decline in life expectancy in a number of SSA countries. This article identifies the reasons for the global shortage of nurses and recommends actions to address the crisis in Africa.