Insights from chemical systems into Turing-type morphogenesis.

In 1952, Alan Turing proposed a theory showing how morphogenesis could occur from a simple two morphogen reaction-diffusion system [Turing, A. M. (1952) Phil. Trans. R. Soc. Lond. A 237, 37-72. (doi:10.1098/rstb.1952.0012)]. While the model is simple, it has found diverse applications in fields such as biology, ecology, behavioural science, mathematics and chemistry. Chemistry in particular has made significant contributions to the study of Turing-type morphogenesis, providing multiple reproducible experimental methods to both predict and study new behaviours and dynamics generated in reaction-diffusion systems. In this review, we highlight the historical role chemistry has played in the study of the Turing mechanism, summarize the numerous insights chemical systems have yielded into both the dynamics and the morphological behaviour of Turing patterns, and suggest future directions for chemical studies into Turing-type morphogenesis. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.

"Ask me what I need": A call for shifting responsibility upwards and creating inclusive learning environments in clinical placement.

BACKGROUND: Ontario's human-rights legislation and institutions' support for students with disabilities have influenced these students' increased enrolment in the postsecondary environment. Yet more attention is paid to in-classroom than to out-of-classroom experiences. Students with disabilities enrolled in nursing are least likely to be accommodated. This has significant implications for access and equity upon graduation, as clinical placements are a bridge between school and employment. OBJECTIVES: To explore clinical instructors' and students who identify with disabilities' perspectives on nursing clinical placements. METHOD: A descriptive case-report was used: interactive take-home diaries were completed and semi-structured interviews were conducted with clinical instructors (n-14) and nursing students with disabilities (n-14) in Ontario. An iterative inductive analysis was undertaken. RESULTS: Three overarching themes were identified: (a) an immovable clinical environment in relation to technology and time, (b) a perceived conflict between nursing and disability identity, and (c) a need to shift responsibility upwards while listening to lived experience. The clinical environment is a highly contested space; different identity groups have distinct roles and differing degrees of power within it. CONCLUSION: Our research calls for a shift in the nursing landscape to be led by education and medical institutions that can build supportive networks, develop clear policies and listen to nursing students with disabilities.

On the possibility of spontaneous chemomechanical oscillations in adsorptive porous media.

We derive general conditions for the emergence of sustained chemomechanical oscillations from a non-oscillatory adsorption/desorption reaction in a gas/solid porous medium. The oscillations arise from the nonlinear response of the solid matrix to the loading of the adsorbed species. More particularly, we prove that, in order for oscillations to occur, adsorption of the gas must in general cause a swelling of the solid matrix. We also investigate the prototypical case of Langmuir kinetics both numerically and analytically.This article is part of the theme issue 'Dissipative structures in matter out of equilibrium: from chemistry, photonics and biology (part 2)'.

Examining predictors of help-seeking behaviours in patients with mood and anxiety symptoms.

Relatively little is known about individual characteristics that factor into the decision to seek help for mood and anxiety symptoms. The current study was undertaken in order to examine factors that predict the likelihood of seeking help for mood and anxiety symptoms amongst a clinical population. Patients (N = 278) referred to a tertiary care clinic in Toronto, Canada were asked about their help-seeking behaviours (HSB) through initial intake assessments and self-administered questionnaires, including the Beck Anxiety Inventory, Anxiety Sensitivity Index, Intolerance of Uncertainty Scale, and Beck Depression Inventory-II. Correlates of anxiety and depression were examined to determine whether they could predict HSB amongst individuals with Generalized Anxiety Disorder with or without comorbid Major Depressive Disorder, as well as Panic Disorder and Social Anxiety Disorder. Psychiatric diagnoses were then examined to determine whether comorbidity and demographic factors impacted HSB. Results indicated that there were significant differences in anxiety and depression correlating mainly with anxiety sensitivity, as a predictor of HSB, and that there is a complex relationship between disorder type and demographic variables. The implications of these findings and suggested targeted interventions are discussed.

Targeting the PI3K/Akt pathway in murine MDS/MPN driven by hyperactive Ras.

Chronic and juvenile myelomonocytic leukemias (CMML and JMML) are myelodysplastic/myeloproliferative neoplasia (MDS/MPN) overlap syndromes that respond poorly to conventional treatments. Aberrant Ras activation because of NRAS, KRAS, PTPN11, CBL and NF1 mutations is common in CMML and JMML. However, no mechanism-based treatments currently exist for cancers with any of these mutations. An alternative therapeutic strategy involves targeting Ras-regulated effector pathways that are aberrantly activated in CMML and JMML, which include the Raf/MEK/ERK and phosphoinositide-3'-OH kinase (PI3K)/Akt cascades. Mx1-Cre, Kras(D12) and Mx1-Cre, Nf1(flox/)(-) mice accurately model many aspects of CMML and JMML. Treating Mx1-Cre, Kras(D12) mice with GDC-0941 (also referred to as pictilisib), an orally bioavailable inhibitor of class I PI3K isoforms, reduced leukocytosis, anemia and splenomegaly while extending survival. However, GDC-0941 treatment attenuated activation of both PI3K/Akt and Raf/MEK/ERK pathways in primary hematopoietic cells, suggesting it could be acting through suppression of Raf/MEK/ERK signals. To interrogate the importance of the PI3K/Akt pathway specifically, we treated mice with the allosteric Akt inhibitor MK-2206. This compound had no effect on Raf/MEK/ERK signaling, yet it also induced robust hematologic responses in Kras and Nf1 mice with MPN. These data support investigating PI3K/Akt pathway inhibitors as a therapeutic strategy in JMML and CMML patients.

Speed of traveling fronts in a sigmoidal reaction-diffusion system.

We study a sigmoidal version of the FitzHugh-Nagumo reaction-diffusion system based on an analytic description using piecewise linear approximations of the reaction kinetics. We completely describe the dynamics of wave fronts and discuss the properties of the speed equation. The speed diagrams show front bifurcations between branches with one, three, or five fronts that differ significantly from the classical FitzHugh-Nagumo model. We examine how the number of fronts and their speed vary with the model parameters. We also investigate numerically the stability of the front solutions in a case when five fronts exist.

Researching "good death" in a Hong Kong palliative care program: a clinical data-mining study.

This study operationalizes and assesses the percentage of "good deaths" achieved among Chinese cancer patients in a palliative care program, the profile of these patients, the relationship between patients with a good death and psychosocial factors, and the differences in background factors, and physical and psychosocial conditions between patients who experienced a good death and those who did not. Clinical data mining was the research method used. Records of deceased cancer patients between 2003 and 2005 in a palliative care unit were the sole data source. Good death was operationally defined as the patient's record indicating no pain (physical) or anxiety (psychological), and having open and honest communication with family (social) in the final assessment by the Support Team Assessment Schedule (STAS) just before death. Using these criteria, about one-fifth of patients (21.5%; 137 out of 638) experienced a good death. Those with a good death were significantly older and were in palliative care longer. Their records also indicated lower levels of constipation, insomnia, oral discomfort, and family anxiety at their first and at their final STAS assessments. Good death was positively associated with recorded indicators of fullness in life, caregivers' acceptance and support, and negatively with reported feelings of upset about changes in the course of their illness. The results heighten awareness among social workers and other healthcare professionals about the value of good death in patients in palliative care. This empirically-based awareness can foster professionals' ability to set intervention objectives to help patients in palliative care achieve this universally accepted goal.

Oscillatory pulses in FitzHugh-Nagumo type systems with cross-diffusion.

We study FitzHugh-Nagumo type reaction-diffusion systems with linear cross-diffusion terms. Based on an analytical description using piecewise linear approximations of the reaction functions, we completely describe the occurrence and properties of wavy pulses, patterns of relevance in several biological contexts, in two prototypical systems. The pulse wave profiles arising in this treatment contain oscillatory tails similar to those in travelling fronts. We find a fundamental, intrinsic feature of pulse dynamics in cross-diffusive systems--the appearance of pulses in the bistable regime when two fixed points exist.

Wave propagation in a FitzHugh-Nagumo-type model with modified excitability.

We examine a generalized FitzHugh-Nagumo (FHN) type model with modified excitability derived from the diffusive Morris-Lecar equations for neuronal activity. We obtain exact analytic solutions in the form of traveling waves using a piecewise linear approximation for the activator and inhibitor reaction terms. We study the existence and stability of waves and find that the inhibitor species exhibits different types of wave forms (fronts and pulses), while the activator wave maintains the usual kink (front) shape. The nonequilibrium Ising-Bloch bifurcation for the wave speed that occurs in the FHN model, where the control parameter is the ratio of inhibitor to activator time scales, persists when the strength of the inhibitor nonlinearity is taken as the bifurcation parameter.

Arm splitting and backfiring of spiral waves in media displaying local mixed-mode oscillations.

The behavior of spiral waves is investigated in a model of reaction-diffusion media supporting local mixed-mode oscillations for a range of values of a control parameter. This local behavior is accompanied by the formation of nodes, at which the arms of the simple spiral waves begin to split. With further parameter changes, this nodal structure loses stability, becoming quite irregular, eventually evolving into turbulence, while the local dynamics increases in complexity. The breakup of the spiral waves arises from a backfiring instability of the nodes induced by the arm splitting. This process of spiral breakup in the presence of mixed-mode oscillations represents an alternative to previously described scenarios of instability of line defects and superspirals in media with period-doubling and quasiperiodic oscillations, respectively.

The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. II. Baseline characteristics of the "prodromal" sample.

The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology. The purpose of this report is to describe the study's "prodromally symptomatic" sample at baseline, i.e., at intake immediately prior to randomization and prior to receiving study medication. Sixty treatment-seeking patients meeting prodromal inclusion criteria were recruited across four sites: New Haven, CT (n=39), Toronto, Ontario (n=9), Calgary, Alberta (n=6), and Chapel Hill, NC (n=6). The sample was young (median age 16), largely male (65%), and came from families with high titers of serious mental illness (44%). Most patients (93%) met criteria for the Attenuated Positive Symptom (APS) prodromal syndrome and presented with significant but nonpsychotic suspiciousness, perceptual aberrations, unusual thought content, and conceptual disorganization. They presented with minimal to mild affective symptoms and substance use/abuse, but they were quite functionally compromised (mean Global Assessment of Functioning (GAF) score=42). The prodromal sample was compared with other clinical-trial samples of adolescent depression, adolescent mania, and first episode schizophrenia. Prodromal patients proved not to be depressed or manic. They were less severely ill than untreated first episode schizophrenia but more severely ill than treated first episode schizophrenia. While not psychotically disabled, these patients nevertheless present with a clinical syndrome. Subsequent reports will detail the effects of drug versus placebo on prodromal symptoms, neuropsychological profile, and the rate of conversion to psychosis.

Pattern formation in a tunable medium: the Belousov-Zhabotinsky reaction in an aerosol OT microemulsion.

Turing structures, standing waves, oscillatory clusters, and accelerating waves have been found in the spatially extended Belousov-Zhabotinsky system dispersed in water droplets of a reverse AOT microemulsion. The variety of patterns is determined by the tunable microstructure of the medium, i.e., by the concentration and size of water droplets. We propose a simple model to describe this system.

Spatial periodic forcing of Turing structures.

Spontaneously evolving Turing structures in the chlorine dioxide-iodine-malonic acid reaction-diffusion system typically exhibit many defects that break the symmetry of the pattern. Periodic spatial forcing interacts with the Turing structures and modifies the pattern symmetry and wavelength. We investigate the role of the amplitude and wavelength of spatial periodic forcing on the hexagonal pattern of Turing structures. Experimental results and numerical simulations reveal that forcing at wavelengths slightly larger than the natural wavelength of the pattern is most effective in removing defects and producing ordered symmetric hexagonal patterns.

Inwardly rotating spiral waves in a reaction-diffusion system.

Almost 30 years have passed since the discovery of concentric (target) and spiral waves in the spatially extended Belousov-Zhabotinsky (BZ) reaction. Since then, rotating spirals and target waves have been observed in a variety of physical, chemical, and biological reaction-diffusion systems. All of these waves propagate out from the spiral center or pacemaker. We report observations of inwardly rotating spirals found in the BZ system dispersed in water droplets of a water-in-oil microemulsion. These "antispirals" were also generated in computer simulations.

Turing pattern formation induced by spatially correlated noise.

The effect of spatially correlated noise on Turing structures is analyzed both experimentally and numerically. Using the photosensitive character of the chlorine dioxide-iodine-malonic acid reaction-diffusion system, spatial randomness is introduced in the system. In the presence of noise, Turing patterns appear and are stable at levels of average illumination that would be more than sufficient to suppress pattern formation in the case of homogeneous illumination.

Dynamics of kinks in one- and two-dimensional hyperbolic models with quasidiscrete nonlinearities.

We study the evolution of fronts in the Klein-Gordon equation when the nonlinear term is inhomogeneous. Extending previous works on homogeneous nonlinear terms, we describe the derivation of an equation governing the front motion, which is strongly nonlinear, and, for the two-dimensional case, generalizes the damped Born-Infeld equation. We study the motion of one- and two-dimensional fronts finding a much richer dynamics than in the homogeneous system case, leading, in most cases, to the stabilization of one phase inside the other. For a one-dimensional front, the function describing the inhomogeneity of the nonlinear term acts as a "potential function" for the motion of the front, i.e., a front initially placed between two of its local maxima asymptotically approaches the intervening minimum. Two-dimensional fronts, with radial symmetry and without dissipation can either shrink to a point in finite time, grow unboundedly, or their radius can oscillate, depending on the initial conditions. When dissipation effects are present, the oscillations either decay spirally or not depending on the value of the damping dissipation parameter. For fronts with a more general shape, we present numerical simulations showing the same behavior.

Resonant suppression of Turing patterns by periodic illumination.

We study the resonant behavior of Turing pattern suppression in a model of the chlorine dioxide-iodine-malonic acid reaction with periodic illumination. The results of simulations based on integration of partial differential equations display resonance at the frequency of autonomous oscillations in the corresponding well stirred system. The resonance in Turing pattern suppression is sharper at lower complexing agent concentration and is affected by the waveform of the periodic driving force. Square wave (on-off) periodic forcing is more effective in suppressing Turing patterns than sinusoidal forcing. We compare the dynamics of periodically forced Turing patterns with the dynamics of periodically forced nonhomogeneous states in a system of two identical coupled cells. Bifurcation analysis based on numerical continuation of the latter system gives good predictions for the boundaries of the major resonance regions of the periodically forced patterns.

Oscillatory clusters in the periodically illuminated, spatially extended Belousov-Zhabotinsky reaction.

Cluster-cluster transitions in the periodically illuminated photosensitive Belousov-Zhabotinsky (BZ) reaction-diffusion system exhibit the same scenario as in the autonomous BZ system with negative global feedback: two-phase clusters <--> three-phase clusters <--> irregular clusters <--> localized clusters. Transitions induced by changing the dark ( TD) or light ( TL) phases of the periodic external square wave illumination are dependent not only on the frequency of illumination at constant TD/TL, but also on the ratio TD/TL at constant frequency (when TD+TL = const).