Novel Fibonacci and non-Fibonacci structure in the sunflower: results of a citizen science experiment.

This citizen science study evaluates the occurrence of Fibonacci structure in the spirals of sunflower (Helianthus annuus) seedheads. This phenomenon has competing biomathematical explanations, and our core premise is that observation of both Fibonacci and non-Fibonacci structure is informative for challenging such models. We collected data on 657 sunflowers. In our most reliable data subset, we evaluated 768 clockwise or anticlockwise parastichy numbers of which 565 were Fibonacci numbers, and a further 67 had Fibonacci structure of a predefined type. We also found more complex Fibonacci structures not previously reported in sunflowers. This is the third, and largest, study in the literature, although the first with explicit and independently checkable inclusion and analysis criteria and fully accessible data. This study systematically reports for the first time, to the best of our knowledge, seedheads without Fibonacci structure. Some of these are approximately Fibonacci, and we found in particular that parastichy numbers equal to one less than a Fibonacci number were present significantly more often than those one more than a Fibonacci number. An unexpected further result of this study was the existence of quasi-regular heads, in which no parastichy number could be definitively assigned.

Rural experiences with mental illness: through the eyes of patients and their families.

People living in rural areas are often faced with multiple, complex, and seemingly insurmountable barriers to receiving appropriate treatment for mental health problems. Some of the barriers identified in the research literature include inaccessibility to mental health providers, stigma, and limited resources in the community. Despite existing data regarding rural patients and their families, little is known about their lived, personal experiences. For this reason, the purpose of this study was to determine the experience of patients and family members who are dealing with mental illness in rural communities. Based on this qualitative analysis of patient and family members' experiences in rural areas, issues surrounding mental health and treatment are accompanied by significant stigma, often left unresolved, and exacerbated by practical challenges which hinder access to proper mental health resources, frequently leaving rural residents to cope with inadequate solutions or seek their own, alternative solutions.

Making a difference in making miracles: common roadblocks to miracle question effectiveness.

This article describes a clinical investigation of student-therapists' use of the miracle question (MQ). Data used for this project came from transcribed role-play videotapes by six student-therapists. Transcripts were coded, and findings highlight challenges that prevent beginning therapists from effectively using the MQ. The primary themes that emerged were problems related to introducing, framing, and following up on the MQ. Practical recommendations are offered for improving therapist training in effective use of the MQ.

The Na+/K+ pump is an important modulator of refractoriness and rotor dynamics in human atrial tissue.

Pharmacological treatment of atrial fibrillation (AF) exhibits limited efficacy. Further developments require a comprehensive characterization of ionic modulators of electrophysiology in human atria. Our aim is to systematically investigate the relative importance of ionic properties in modulating excitability, refractoriness, and rotor dynamics in human atria before and after AF-related electrical remodeling (AFER). Computer simulations of single cell and tissue atrial electrophysiology were conducted using two human atrial action potential (AP) models. Changes in AP, refractory period (RP), conduction velocity (CV), and rotor dynamics caused by alterations in key properties of all atrial ionic currents were characterized before and after AFER. Results show that the investigated human atrial electrophysiological properties are primarily modulated by maximal value of Na(+)/K(+) pump current (G(NaK)) as well as conductances of inward rectifier potassium current (G(K1)) and fast inward sodium current (G(Na)). G(NaK) plays a fundamental role through both electrogenic and homeostatic modulation of AP duration (APD), APD restitution, RP, and reentrant dominant frequency (DF). G(K1) controls DF through modulation of AP, APD restitution, RP, and CV. G(Na) is key in determining DF through alteration of CV and RP, particularly in AFER. Changes in ionic currents have qualitatively similar effects in control and AFER, but effects are smaller in AFER. The systematic analysis conducted in this study unravels the important role of the Na(+)/K(+) pump current in determining human atrial electrophysiology.

A probabilistic approach to identify putative drug targets in biochemical networks.

Network-based drug design holds great promise in clinical research as a way to overcome the limitations of traditional approaches in the development of drugs with high efficacy and low toxicity. This novel strategy aims to study how a biochemical network as a whole, rather than its individual components, responds to specific perturbations in different physiological conditions. Proteins exerting little control over normal cells and larger control over altered cells may be considered as good candidates for drug targets. The application of network-based drug design would greatly benefit from using an explicit computational model describing the dynamics of the system under investigation. However, creating a fully characterized kinetic model is not an easy task, even for relatively small networks, as it is still significantly hampered by the lack of data about kinetic mechanisms and parameters values. Here, we propose a Monte Carlo approach to identify the differences between flux control profiles of a metabolic network in different physiological states, when information about the kinetics of the system is partially or totally missing. Based on experimentally accessible information on metabolic phenotypes, we develop a novel method to determine probabilistic differences in the flux control coefficients between the two observable phenotypes. Knowledge of how differences in flux control are distributed among the different enzymatic steps is exploited to identify points of fragility in one of the phenotypes. Using a prototypical cancerous phenotype as an example, we demonstrate how our approach can assist researchers in developing compounds with high efficacy and low toxicity.

Telehealth and rural depression: physician and patient perspectives.

Due to a shortage of mental health professionals (MHPs) in rural areas, primary care physicians (PCP) are often the first, and in many cases, the only providers of depression treatment for rural individuals. This study was an investigation of the acceptability of behavioral telehealth to PCPs and patients with depression as a way of making mental health treatments more accessible to rural patients. The researchers conducted 10 focus groups across rural Nebraska with PCPs and patients they had treated for depression. A qualitative multiple-case study approach was used to analyze the transcriptions. The participants felt that behavioral telehealth is a reasonable solution to the access-to-care problem. They expressed concern that professional and therapeutic relationships would be difficult to maintain at a distance and they provided suggestions for how to preserve these relationships when using technology to deliver treatment such as focusing on fostering collaborative relationships between MHPs and PCPs. It is essential for MHPs and PCPs to develop and maintain a collaborative working relationship that will facilitate frequent communication.

Capturing the essence of a metabolic network: a flux balance analysis approach.

As genome-scale metabolic reconstructions emerge, tools to manage their size and complexity will be increasingly important. Flux balance analysis (FBA) is a constraint-based approach widely used to study the metabolic capabilities of cellular or subcellular systems. FBA problems are highly underdetermined and many different phenotypes can satisfy any set of constraints through which the metabolic system is represented. Two of the main concerns in FBA are exploring the space of solutions for a given metabolic network and finding a specific phenotype which is representative for a given task such as maximal growth rate. Here, we introduce a recursive algorithm suitable for overcoming both of these concerns. The method proposed is able to find the alternate optimal patterns of active reactions of an FBA problem and identify the minimal subnetwork able to perform a specific task as optimally as the whole. Our method represents an alternative to and an extension of other approaches conceived for exploring the space of solutions of an FBA problem. It may also be particularly helpful in defining a scaffold of reactions upon which to build up a dynamic model, when the important pathways of the system have not yet been well-defined.

Considerations for powering a clinical proteomics study: Normal variability in the human plasma proteome.

Proteomics is increasingly being applied to the human plasma proteome to identify biomarkers of disease for use in non-invasive assays. 2-D DIGE, simultaneously analysing thousands of protein spots quantitatively and maintaining protein isoform information, is one technique adopted. Sufficient numbers of samples must be analysed to achieve statistical power; however, few reported studies have analysed inherent variability in the plasma proteome by 2-D DIGE to allow power calculations. This study analysed plasma from 60 healthy volunteers by 2-D DIGE. Two samples were taken, 7 days apart, allowing estimation of sensitivity of detection of differences in spot intensity between two groups using either a longitudinal (paired) or non-paired design. Parameters for differences were: two-fold normalised volume change, α of 0.05 and power of 0.8. Using groups of 20 samples, alterations in 1742 spots could be detected with longitudinal sampling, and in 1206 between non-paired groups. Interbatch gel variability was small relative to the detection parameters, indicating robustness and reproducibility of 2-D DIGE for analysing large sample sets. In summary, 20 samples can allow detection of a large number of proteomic alterations by 2-D DIGE in human plasma, the sensitivity of detecting differences was greatly improved by longitudinal sampling and the technology was robust across batches.

Beyond the genome--SMi Conference 27-28 January 2003, London, UK.

Over a decade of astonishing developments, genomics and proteomics have promised a fundamentally new approach to drug discovery. Although there has been an undeniable increase in the range of potential targets available, this has not led to an increased output of the drug discovery pipeline into the clinic. With tighter markets and increasing competition, the major pharmaceutical companies are under intense pressure to achieve rapid, concrete delivery of those early promises, but there remain acute problems in the genes-to-drugs pipeline. This meeting showcased a range of novel approaches from proteomics and bioinformatics to address these problems. A common theme in the range of proteomics offerings was the prioritization of potential novel targets on the basis of their accessibility to drugs and their functional link to disease phenotypes. Informatics and in silico offerings also concentrated on fast, accurate, drug-focused workflows built on large integrative databases and novel data-mined algorithms.

Disease in endangered metapopulations: the importance of alternative hosts.

Conventional applications of metapopulation theory have suggested that increasing migration between patches is usually good for conservation. A recent analysis by Hess has pointed out a possible exception to this: when infectious disease is present, migration may promote disease spread and therefore increase local extinction. We extend Hess's model to discuss this problem: when infections have spilled over from more abundant alternative hosts. This is often the case for species of conservation concern, and we find that Hess's conclusions must be substantially modified. We use deterministic analytic and stochastic numerical approaches to show that movement between patches will rarely have a negative impact, even when the probability of external infection is low.

Is microsatellite mutational asymmetry detectable in allele frequency distributions?

We explore the mutational processes giving rise to microsatellite diversity by analysing allele lengths in 6045 human microsatellite markers drawn from the CEPH panel. Assuming a general mutation-drift process generating this diversity, the bias of the mutation distribution cannot be directly estimated from such data. However, inferences can still be made about the degree and sign of the asymmetry of the mutation distribution. We consider statistics based on moments of the observed length distribution, and derive their relevant analytical properties, showing that they have a high sampling variance. We conclude that moment estimators applied to allele length frequencies within the CEPH database could not be used to reject a null hypothesis of no bias even if bias was present. However, an order parameter does provide evidence of asymmetrically biased mutation: there is an unambiguous preponderance of alleles in which the shortest locus is the most frequent. It will be important to further characterize the sampling properties of such order parameters to estimate the magnitude of any mutation bias and the sensitivity of this estimation to the mutation model assumed.