Nurse Practitioners in Critical Care Transport.

The inclusion of nurse practitioners (NPs) in critical care transport teams has the potential to enhance patient care and improve team operations. NPs can manage complex clinical situations during transport and excel in various roles such as leadership, education, mentoring, research, quality improvement, and clinical expertise. As we navigate the evolving landscape of critical care transport, it is crucial to explore the potential benefits offered by NPs. Their distinct skills and experiences effectively position them to improve patient outcomes, enhance team performance, and contribute to health care's financial sustainability. This article discusses the role of NPs in critical care transport, providing insight into their current uses, and recommendations for optimal use.

Two-stage patterning dynamics in conifer cotyledon whorl morphogenesis.

Background and Aims: Conifer embryos, unlike those of monocots or dicots, have variable numbers of cotyledons, even within the same species. Cotyledons form in a single whorl on a dome-shaped embryo. The closely spaced cotyledons are not found outside this ring, indicating a radial control on where they can form. Polar transport of the hormone auxin affects outgrowth of distinct cotyledons, but not the radial aspect of the whorl or the within-whorl spacing between cotyledons. A quantitative model of plant growth regulator patterning is needed to understand the dynamics of this complex morphogenetic process. Methods: A two-stage reaction-diffusion model is developed for the spatial patterning of growth regulators on the embryo surface, with a radial pattern (P1) constraining the shorter-wavelength cotyledon pattern (P2) to a whorl. These patterns drive three-dimensional (3-D) morphogenesis by catalysing local surface growth. Key Results: Growth driven by P2 generates single whorls across the experimentally observed range of two to 11 cotyledons, as well as the circularly symmetric response to auxin transport interference. These computations are the first corroboration of earlier theoretical proposals for hierarchical control of whorl formation. The model generates the linear relationship between cotyledon number and embryo diameter observed experimentally. This accounts for normal integer cotyledon number selection, as well as the less common cotyledon fusings and splittings observed experimentally. Flattening of the embryo during development may affect the upward outgrowth angle of the cotyledons. Conclusions: Cotyledon morphogenesis is more complex geometrically in conifers than in angiosperms, involving 2-D patterning which deforms a surface in three dimensions. This work develops a quantitative framework for understanding the growth and patterning dynamics involved in conifer cotyledon development, and applies more generally to the morphogenesis of whorls with many primordia.

Forced evolution in silico by artificial transposons and their genetic operators: The ant navigation problem.

Modern evolutionary computation utilizes heuristic optimizations based upon concepts borrowed from the Darwinian theory of natural selection. Their demonstrated efficacy has reawakened an interest in other aspects of contemporary biology as an inspiration for new algorithms. However, amongst the many excellent candidates for study, contemporary models of biological macroevolution attract special attention. We believe that a vital direction in this field must be algorithms that model the activity of "genomic parasites", such as transposons, in biological evolution. Many evolutionary biologists posit that it is the co-evolution of populations with their genomic parasites that permits the high efficiency of evolutionary searches found in the living world. This publication is our first step in the direction of developing a minimal assortment of algorithms that simulate the role of genomic parasites. Specifically, we started in the domain of genetic algorithms (GA) and selected the Artificial Ant Problem as a test case. This navigation problem is widely known as a classical benchmark test and possesses a large body of literature. We add new objects to the standard toolkit of GA - artificial transposons and a collection of operators that operate on them. We define these artificial transposons as a fragment of an ant's code with properties that cause it to stand apart from the rest. The minimal set of operators for transposons is a transposon mutation operator, and a transposon reproduction operator that causes a transposon to multiply within the population of hosts. An analysis of the population dynamics of transposons within the course of ant evolution showed that transposons are involved in the processes of propagation and selection of blocks of ant navigation programs. During this time, the speed of evolutionary search increases significantly. We concluded that artificial transposons, analogous to real transposons, are truly capable of acting as intelligent mutators that adapt in response to an evolutionary problem in the course of co-evolution with their hosts.

Cinematherapy and film as an educational tool in undergraduate psychiatry teaching: a case report and review of the literature.

Film possesses an extraordinary power and offers an unrivalled medium for entertainment and escapism. There are many films that revolve around a mental illness theme and the medical specialty that most commonly features in motion picture is psychiatry. Over the last few decades films have become increasingly used as an educational tool in the teaching of psychiatry topics such as mental state examination to undergraduate students. Above and beyond its utility in pedagogy, film also has the power to heal and the term cinematherapy has been coined to reflect this. Indeed, there are case studies of people with first-hand experience of psychopathology who report that watching films with a mental illness theme has contributed to their recovery. We provide a first person narrative from an individual with schizophrenia in which he expounds on the concepts of cinematherpy and metaphorical imagery in films which theme on psychosis.

Using evolutionary computations to understand the design and evolution of gene and cell regulatory networks.

This paper surveys modeling approaches for studying the evolution of gene regulatory networks (GRNs). Modeling of the design or 'wiring' of GRNs has become increasingly common in developmental and medical biology, as a means of quantifying gene-gene interactions, the response to perturbations, and the overall dynamic motifs of networks. Drawing from developments in GRN 'design' modeling, a number of groups are now using simulations to study how GRNs evolve, both for comparative genomics and to uncover general principles of evolutionary processes. Such work can generally be termed evolution in silico. Complementary to these biologically-focused approaches, a now well-established field of computer science is Evolutionary Computations (ECs), in which highly efficient optimization techniques are inspired from evolutionary principles. In surveying biological simulation approaches, we discuss the considerations that must be taken with respect to: (a) the precision and completeness of the data (e.g. are the simulations for very close matches to anatomical data, or are they for more general exploration of evolutionary principles); (b) the level of detail to model (we proceed from 'coarse-grained' evolution of simple gene-gene interactions to 'fine-grained' evolution at the DNA sequence level); (c) to what degree is it important to include the genome's cellular context; and (d) the efficiency of computation. With respect to the latter, we argue that developments in computer science EC offer the means to perform more complete simulation searches, and will lead to more comprehensive biological predictions.

Body plan evolvability: The role of variability in gene regulatory networks.

Recent computational modeling of early fruit fly (Drosophila) development has characterized the degree to which gene regulation networks can be robust to natural variability. In the first few hours of development, broad spatial gradients of maternally derived transcription factors activate embryonic gap genes. These gap patterns determine the subsequent segmented insect body plan through pair-rule gene expression. Gap genes are expressed with greater spatial precision than the maternal patterns. Computational modeling of the gap-gap regulatory interactions provides a mechanistic understanding for this robustness to maternal variability in wild-type (WT) patterning. A long-standing question in evolutionary biology has been how a system which is robust, such as the developmental program creating any particular species' body plan, is also evolvable, i.e. how can a system evolve or speciate, if the WT form is strongly buffered and protected? In the present work, we use the WT model to explore the breakdown of such Waddington-type 'canalization'. What levels of variability will push the system out of the WT form; are there particular pathways in the gene regulatory mechanism which are more susceptible to losing the WT form; and when robustness is lost, what types of forms are most likely to occur (i.e. what forms lie near the WT)? Manipulating maternal effects in several different pathways, we find a common gap 'peak-to-step' pattern transition in the loss of WT. We discuss these results in terms of the evolvability of insect segmentation, and in terms of experimental perturbations and mutations which could test the model predictions. We conclude by discussing the prospects for using continuum models of pattern dynamics to investigate a wider range of evo-devo problems.

Reaction-diffusion patterns in plant tip morphogenesis: bifurcations on spherical caps.

We study a chemical reaction-diffusion model (the Brusselator) for pattern formation on developing plant tips. A family of spherical cap domains is used to represent tip flattening during development. Applied to conifer embryos, we model the chemical prepatterning underlying cotyledon ("seed leaf") formation, and demonstrate the dependence of patterns on tip flatness, radius, and precursor concentrations. Parameters for the Brusselator in spherical cap domains can be chosen to give supercritical pitchfork bifurcations of patterned solutions of the nonlinear reaction-diffusion system that correspond to the cotyledon patterns that appear on the flattening tips of conifer embryos.

Size regulation of the lateral organ initiation zone and its role in determining cotyledon number in conifers.

Introduction: Unlike monocots and dicots, many conifers, particularly Pinaceae, form three or more cotyledons. These are arranged in a whorl, or ring, at a particular distance from the embryo tip, with cotyledons evenly spaced within the ring. The number of cotyledons, nc, varies substantially within species, both in clonal cultures and in seed embryos. nc variability reflects embryo size variability, with larger diameter embryos having higher nc. Correcting for growth during embryo development, we extract values for the whorl radius at each nc. This radius, corresponding to the spatial pattern of cotyledon differentiation factors, varies over three-fold for the naturally observed range of nc. The current work focuses on factors in the patterning mechanism that could produce such a broad variability in whorl radius. Molecularly, work in Arabidopsis has shown that the initiation zone for leaf primordia occurs at a minimum between inhibitor zones of HD-ZIP III at the shoot apical meristem (SAM) tip and KANADI (KAN) encircling this farther from the tip. PIN1-auxin dynamics within this uninhibited ring form auxin maxima, specifying primordia initiation sites. A similar mechanism is indicated in conifer embryos by effects on cotyledon formation with overexpression of HD-ZIP III inhibitors and by interference with PIN1-auxin patterning. Methods: We develop a mathematical model for HD-ZIP III/KAN spatial localization and use this to characterize the molecular regulation that could generate (a) the three-fold whorl radius variation (and associated nc variability) observed in conifer cotyledon development, and (b) the HD-ZIP III and KAN shifts induced experimentally in conifer embryos and in Arabidopsis. Results: This quantitative framework indicates the sensitivity of mechanism components for positioning lateral organs closer to or farther from the tip. Positional shifting is most readily driven by changes to the extent of upstream (meristematic) patterning and changes in HD-ZIP III/KAN mutual inhibition, and less efficiently driven by changes in upstream dosage or the activation of HD-ZIP III. Sharper expression boundaries can also be more resistant to shifting than shallower expression boundaries. Discussion: The strong variability seen in conifer nc (commonly from 2 to 10) may reflect a freer variation in regulatory interactions, whereas monocot (nc = 1) and dicot (nc = 2) development may require tighter control of such variation. These results provide direction for future quantitative experiments on the positional control of lateral organ initiation, and consequently on plant phyllotaxy and architecture.

A decade of outcomes: The evolution of an australasian outcomes collaboration for chronic pain services.

Since the establishment of the electronic Persistent Pain Outcomes Collaboration (ePPOC) in 2013, ongoing improvements in benchmarking and quality improvement activities have provided the opportunity for ePPOC to grow to support more than one hundred adult and pediatric services delivering care to Individuals living with persistent pain throughout Australia and New Zealand. These improvements straddle multiple domains, including benchmarking and indicators reports, internal and external research collaboration and the integration of quality improvement initiatives with pain services. This paper outlines improvements undertaken and lessons learned in relation to the growth and maintenance of a comprehensive outcomes registry and its articulation with pain services and the wider pain sector.

Factors associated with general practitioner visits for pain in people experiencing chronic pain.

Introduction Patients with chronic pain (CP) are frequent users of general practitioners (GPs). Aim This study aimed to assess factors associated with the rate of GP visits related to pain in patients with CP. Methods This study used data collected by adult specialist pain management services (SPMS) that participated in the electronic Persistent Pain Outcomes Collaboration (ePPOC) in Australia. Adult patients (18 years or older) with CP (duration greater than 3 months) who were referred to SPMS from the calendar year 2015-2021 were included (N = 84 829). Results Patients who reported severe anxiety, stress, pain, pain interference, pain catastrophising and severely impaired pain self-efficacy were more likely to seek help from a GP. Patients with longer pain duration had a lower rate of GP visits. The rate of GP visits was 1.22 (IRR = 1.22, 95% CI: 1.19, 1.26) times higher in patients with severe pain severity, compared to patients with mild pain severity. Patients who used opioids were more likely to visit a GP (IRR = 1.32, 95% CI: 1.30, 1.34) than those who were not using opioids. Discussions More than half of the adult CP patients had greater than three GP visits in the 3 months before referral. This study would indicate that some patients may attend their GP to seek an opioid prescription. Given the rising use of opioids nationally, future study is required on opioid users' GP visitation practices. Additionally, the inverse association between pain duration and the rate of GP visits warrants further exploration.

Gene expression noise in spatial patterning: hunchback promoter structure affects noise amplitude and distribution in Drosophila segmentation.

Positional information in developing embryos is specified by spatial gradients of transcriptional regulators. One of the classic systems for studying this is the activation of the hunchback (hb) gene in early fruit fly (Drosophila) segmentation by the maternally-derived gradient of the Bicoid (Bcd) protein. Gene regulation is subject to intrinsic noise which can produce variable expression. This variability must be constrained in the highly reproducible and coordinated events of development. We identify means by which noise is controlled during gene expression by characterizing the dependence of hb mRNA and protein output noise on hb promoter structure and transcriptional dynamics. We use a stochastic model of the hb promoter in which the number and strength of Bcd and Hb (self-regulatory) binding sites can be varied. Model parameters are fit to data from WT embryos, the self-regulation mutant hb(14F), and lacZ reporter constructs using different portions of the hb promoter. We have corroborated model noise predictions experimentally. The results indicate that WT (self-regulatory) Hb output noise is predominantly dependent on the transcription and translation dynamics of its own expression, rather than on Bcd fluctuations. The constructs and mutant, which lack self-regulation, indicate that the multiple Bcd binding sites in the hb promoter (and their strengths) also play a role in buffering noise. The model is robust to the variation in Bcd binding site number across a number of fly species. This study identifies particular ways in which promoter structure and regulatory dynamics reduce hb output noise. Insofar as many of these are common features of genes (e.g. multiple regulatory sites, cooperativity, self-feedback), the current results contribute to the general understanding of the reproducibility and determinacy of spatial patterning in early development.

In silico evolution of gene cooption in pattern-forming gene networks.

Gene recruitment or cooption occurs when a gene, which may be part of an existing gene regulatory network (GRN), comes under the control of a new regulatory system. Such re-arrangement of pre-existing networks is likely more common for increasing genomic complexity than the creation of new genes. Using evolutionary computations (EC), we investigate how cooption affects the evolvability, outgrowth and robustness of GRNs. We use a data-driven model of insect segmentation, for the fruit fly Drosophila, and evaluate fitness by robustness to maternal variability-a major constraint in biological development. We compare two mechanisms of gene cooption: a simpler one with gene Introduction and Withdrawal operators; and one in which GRN elements can be altered by transposon infection. Starting from a minimal 2-gene network, insufficient for fitting the Drosophila gene expression patterns, we find a general trend of coopting available genes into the GRN, in order to better fit the data. With the transposon mechanism, we find co-evolutionary oscillations between genes and their transposons. These oscillations may offer a new technique in EC for overcoming premature convergence. Finally, we comment on how a differential equations (in contrast to Boolean) approach is necessary for addressing realistic continuous variation in biochemical parameters.

Quantification reveals early dynamics in Drosophila maternal gradients.

The Bicoid (Bcd) protein is a primary determinant of early anterior-posterior (AP) axis specification in Drosophila embryogenesis. This morphogen is spatially distributed in an anterior-high gradient, and affects particular AP cell fates in a concentration-dependent manner. The early distribution and dynamics of the bicoid (bcd) mRNA, the source for the Bcd protein gradient, is not well understood, leaving a number of open questions for how Bcd positional information develops and is regulated. Confocal microscope images of whole early embryos, stained for bcd mRNA or the Staufen (Stau) protein involved in its transport, were processed to extract quantitative AP intensity profiles at two depths (apical-under the embryo surface but above the nuclear layer; and basal-below the nuclei). Each profile was quantified by a two- (or three-) exponential equation. The parameters of these equations were used to analyze the early developmental dynamics of bcd. Analysis of 1D profiles was compared with 2D intensity surfaces from the same images. This approach reveals strong early changes in bcd and Stau, which appear to be coordinated. We can unambiguously discriminate three stages in early development using the exponential parameters: pre-blastoderm (1-9 cleavage cycle, cc), syncytial blastoderm (10-13 cc) and cellularization (from 14A cc). Key features which differ in this period are how fast the first exponential (anterior component) of the apical profile drops with distance and whether it is higher or lower than the basal first exponential. We can further discriminate early and late embryos within the pre-blastoderm stage, depending on how quickly the anterior exponential drops. This relates to the posterior-wards spread of bcd in the first hour of development. Both bcd and Stau show several redistributions in the head cytoplasm, quite probably related to nuclear activity: first shifting inwards towards the core plasm, forming either protrusions (early pre-blastoderm) or round aggregations (early nuclear cleavage cycles, cc, 13 and 14), then moving to the embryo surface and spreading posteriorly. These movements are seen both with the 2D surface study and the 1D profile analysis. The continued spreading of bcd can be tracked from the time of nuclear layer formation (later pre-blastoderm) to the later syncytial blastoderm stages by the progressive loss of steepness of the apical anterior exponential (for both bcd and Stau). Finally, at the beginning of cc14 (cellularization stage) we see a distinctive flip from the basal anterior gradient being higher to the apical gradient being higher (for both bcd and Stau). Quantitative analysis reveals substantial (and correlated) bcd and Stau redistributions during early development, supporting that the distribution and dynamics of bcd mRNA are key factors in the formation and maintenance of the Bcd protein morphogenetic gradient. This analysis reveals the complex and dynamic nature of bcd redistribution, particularly in the head cytoplasm. These resemble observations in oogenesis; their role and significance have yet to be clarified. The observed co-localization during redistribution of bcd and Stau may indicate the involvement of active transport.

The role of chemical dynamics in plant morphogenesis(1).

In biological development, the generation of shape is preceded by the spatial localization of growth factors. Localization, and how it is maintained or changed during the process of growth, determines the shapes produced. Mathematical models have been developed to investigate the chemical, mechanical and transport properties involved in plant morphogenesis. These synthesize biochemical and biophysical data, revealing underlying principles, especially the importance of dynamics in generating form. Chemical kinetics has been used to understand the constraints on reaction and transport rates to produce localized concentration patterns. This approach is well developed for understanding de novo pattern formation, pattern spacing and transitions from one pattern to another. For plants, growth is continual, and a key use of the theory is in understanding the feedback between patterning and growth, especially for morphogenetic events which break symmetry, such as tip branching. Within the context of morphogenetic modelling in general, the present review gives a brief history of chemical patterning research and its particular application to shape generation in plant development.

Spatial bistability generates hunchback expression sharpness in the Drosophila embryo.

During embryonic development, the positional information provided by concentration gradients of maternal factors directs pattern formation by providing spatially dependent cues for gene expression. In the fruit fly, Drosophila melanogaster, a classic example of this is the sharp on-off activation of the hunchback (hb) gene at midembryo, in response to local concentrations of the smooth anterior-posterior Bicoid (Bcd) gradient. The regulatory region for hb contains multiple binding sites for the Bcd protein as well as multiple binding sites for the Hb protein. Some previous studies have suggested that Bcd is sufficient for properly sharpened Hb expression, yet other evidence suggests a need for additional regulation. We experimentally quantified the dynamics of hb gene expression in flies that were wild-type, were mutant for hb self-regulation or Bcd binding, or contained an artificial promoter construct consisting of six Bcd and two Hb sites. In addition to these experiments, we developed a reaction-diffusion model of hb transcription, with Bcd cooperative binding and hb self-regulation, and used Zero Eigenvalue Analysis to look for multiple stationary states in the reaction network. Our model reproduces the hb developmental dynamics and correctly predicts the mutant patterns. Analysis of our model indicates that the Hb sharpness can be produced by spatial bistability, in which hb self-regulation produces two stable levels of expression. In the absence of self-regulation, the bistable behavior vanishes and Hb sharpness is disrupted. Bcd cooperative binding affects the position where bistability occurs but is not itself sufficient for a sharp Hb pattern. Our results show that the control of Hb sharpness and positioning, by hb self-regulation and Bcd cooperativity, respectively, are separate processes that can be altered independently. Our model, which matches the changes in Hb position and sharpness observed in different experiments, provides a theoretical framework for understanding the data and in particular indicates that spatial bistability can play a central role in threshold-dependent reading mechanisms of positional information.

Provision of continued professional development for non-medical prescribers within a South of England Strategic Health Authority: a report on a training needs analysis.

AIMS: This paper reports on a Training Needs Analysis for Non-Medical Prescribers commissioned by a south of England Strategic Health Authority. BACKGROUND: The aim of the TNA was to inform future policy, educational provision and practice development and provide nurse managers with significant information on the perceived Continuing Professional Development (CPD) needs of the non-medical prescribers. METHODS: Data were collected from a sample of 270 non-medical prescribers using an in-depth questionnaire, and telephone interviews with a purposive sample of 11 key stakeholders. RESULTS: The findings report: * The qualifications that non-medical prescribers possess. * The level of confidence described by the non-medical prescribers in their role. * What non-medical prescribers identify as their present and future CPD requirements in relation to prescribing. * What education and training provision non-medical prescribers have attended in relation to their prescribing role since qualifying. CONCLUSIONS: The findings suggest, first that short courses that were specific to the non-medical prescribers role were considered to be the most popular and useful. However, courses needed to be advertised well in advance. Second, training gaps were identified. IMPLICATIONS FOR NURSING MANAGEMENT: Pharmacology and prescribing are rapidly changing and require regular CPD in order to keep up to date with the latest developments. Non-medical prescribing is a comparatively new innovation to the NHS, therefore those who are not medically qualified need mentorship from experienced prescribers, as well as the encouragement from nurse managers to be confident prescribers themselves and enhance patient care.

Pattern selection in plants: coupling chemical dynamics to surface growth in three dimensions.

BACKGROUND AND AIMS: A study is made by computation of the interplay between the pattern formation of growth catalysts on a plant surface and the expansion of the surface to generate organismal shape. Consideration is made of the localization of morphogenetically active regions, and the occurrence within them of symmetry-breaking processes such as branching from an initially dome-shaped tip or meristem. Representation of a changing and growing three-dimensional shape is necessary, as two-dimensional work cannot distinguish, for example, formation of an annulus from dichotomous branching. METHODS: For the formation of patterns of chemical concentrations, the Brusselator reaction-diffusion model is used, applied on a hemispherical shell and generating patterns that initiate as surface spherical harmonics. The initial shape is hemispherical, represented as a mesh of triangles. These are combined into finite elements, each made up of all the triangles surrounding each node. Chemical pattern is converted into shape change by moving nodes outwards according to the concentration of growth catalyst at each, to relieve misfits caused by area increase of the finite element. New triangles are added to restore the refinement of the mesh in rapidly growing regions. KEY RESULTS: The postulated mechanism successfully generates: tip growth (or stalk extension by an apical meristem) to ten times original hemisphere height; tip flattening and resumption of apical advance; and dichotomous branching and higher-order branching to make whorled structures. Control of the branching plane in successive dichotomous branchings is tackled with partial success and clarification of the issues. CONCLUSIONS: The representation of a growing plant surface in computations by an expanding mesh that has no artefacts constraining changes of shape and symmetry has been achieved. It is shown that one type of pattern-forming mechanism, Turing-type reaction-diffusion, acting within a surface to pattern a growth catalyst, can generate some of the most important types of morphogenesis in plant development.

Two-Exponential Models of Gene Expression Patterns for Noisy Experimental Data.

Spatial pattern formation of the primary anterior-posterior morphogenetic gradient of the transcription factor Bicoid (Bcd) has been studied experimentally and computationally for many years. Bcd specifies positional information for the downstream segmentation genes, affecting the fly body plan. More recently, a number of researchers have focused on the patterning dynamics of the underlying bcd messenger RNA (mRNA) gradient, which is translated into Bcd protein. New, more accurate techniques for visualizing bcd mRNA need to be combined with quantitative signal extraction techniques to reconstruct the bcd mRNA distribution. Here, we present a robust technique for quantifying gradients with a two-exponential model. This approach (1) has natural, biologically relevant parameters and (2) is invariant to linear transformations of the data arising due to variation in experimental conditions (e.g., microscope settings, nonspecific background signal). This allows us to quantify bcd mRNA gradient variability from embryo to embryo (important for studying the robustness of developmental regulatory networks); sort out atypical gradients; and classify embryos to developmental stage by quantitative gradient parameters.

Sharp borders from fuzzy gradients.

Critical boundaries in the early Drosophila embryo are set by morphogenetic gradients. A new quantitative study shows that the placement of one such boundary is more accurate than the gradient thought to set it. Genetic analysis of the accuracy of the process implicates a gene not previously thought to be involved.