Ecological non-linear state space model selection via adaptive particle Markov chain Monte Carlo (AdPMCMC)

We develop a novel advanced Particle Markov chain Monte Carlo algorithm that is capable of sampling from the posterior distribution of non-linear state space models for both the unobserved latent states and the unknown model parameters. We apply this novel methodology to five population growth models, including models with strong and weak Allee effects, and test if it can efficiently sample from the complex likelihood surface that is often associated with these models. Utilising real and also synthetically generated data sets we examine the extent to which observation noise and process error may frustrate efforts to choose between these models. Our novel algorithm involves an Adaptive Metropolis proposal combined with an SIR Particle MCMC algorithm (AdPMCMC). We show that the AdPMCMC algorithm samples complex, high-dimensional spaces efficiently, and is therefore superior to standard Gibbs or Metropolis Hastings algorithms that are known to converge very slowly when applied to the non-linear state space ecological models considered in this paper. Additionally, we show how the AdPMCMC algorithm can be used to recursively estimate the Bayesian Cram\'er-Rao Lower Bound of Tichavsk\'y (1998). We derive expressions for these Cram\'er-Rao Bounds and estimate them for the models considered. Our results demonstrate a number of important features of common population growth models, most notably their multi-modal posterior surfaces and dependence between the static and dynamic parameters. We conclude by sampling from the posterior distribution of each of the models, and use Bayes factors to highlight how observation noise significantly diminishes our ability to select among some of the models, particularly those that are designed to reproduce an Allee effect

Keratoconus: cross-linking the window of the eye

Keratoconus is a condition in which the cornea progressively thins and weakens, leading to severe, irregular astigmatism and a significant reduction in quality of life. Although the precise cause of keratoconus is still not known, biochemical and structural studies indicate that overactive enzymes within the cornea break down the constituent proteins (collagen and proteoglycans) and cause the tissue to weaken. As the disease develops, collagen fibres slip past each other and are redistributed across the cornea, causing it to change shape. In recent years, it was discovered that the photochemical induction of cross-links within the corneal extracellular matrix, through the use of riboflavin and ultraviolet (UVA) light, could increase the strength and enzymatic resistance of the tissue and thereby halt keratoconus progression. Worldwide acceptance and use of riboflavin/UVA corneal cross-linking therapy for halting keratoconus progression has increased rapidly, in accordance with the growing body of evidence supporting its long-term effectiveness. This review focusses on the inception of riboflavin/UVA corneal cross-linking therapy for keratoconus, its clinical effectiveness and the latest scientific advances aimed at reducing patient treatment time, improving patient comfort and increasing patient eligibility for treatment

Assessing different causes of crown-of-thorns starfish outbreaks and appropriate responses for management on the Great Barrier Reef

The crown-of-thorns starfish Acanthaster planci (COTS) has contributed greatly to declines in coral cover on Australia's Great Barrier Reef, and remains one of the major acute disturbances on Indo-Pacific coral reefs. Despite uncertainty about the underlying causes of outbreaks and the management responses that might address them, few studies have critically and directly compared competing hypotheses. This study uses qualitative modelling to compare hypotheses relating to outbreak initiation, explicitly considering the potential role of positive feedbacks, elevated nutrients, and removal of starfish predators by fishing. When nutrients and fishing are considered in isolation, the models indicate that a range of alternative hypotheses are capable of explaining outbreak initiation with similar levels of certainty. The models also suggest that outbreaks may be caused by multiple factors operating simultaneously, rather than by single proximal causes. As the complexity and realism of the models increased, the certainty of outcomes decreased, but key areas that require further research to improve the structure of the models were identified. Nutrient additions were likely to result in outbreaks only when COTS larvae alone benefitted from nutrients. Similarly, the effects of fishing on the decline of corals depended on the complexity of interactions among several categories of fishes. Our work suggests that management approaches which seek to be robust to model structure uncertainty should allow for multiple potential causes of outbreaks. Monitoring programs can provide tests of alternative potential causes of outbreaks if they specifically monitor all key taxa at reefs that are exposed to appropriate combinations of potential causal factors

The structural role of elastic fibres in the cornea investigated using a mouse model for Marfan syndrome

Purpose: The presence of fibrillin-rich elastic fibers in the cornea has been overlooked in recent years. The aim of the current study was to elucidate their functional role using a mouse model for Marfan syndrome, defective in fibrillin-1, the major structural component of the microfibril bundles that constitute most of the elastic fibers. Methods: Mouse corneas were obtained from animals with a heterozygous fibrillin-1 mutation (Fbn1+/−) and compared to wild type controls. Corneal thickness and radius of curvature were calculated using optical coherence tomography microscopy. Elastic microfibril bundles were quantified and visualized in three-dimensions using serial block face scanning electron microscopy. Transmission electron microscopy was used to analyze stromal ultrastructure and proteoglycan distribution. Center-to-center average interfibrillar spacing was determined using x-ray scattering. Results: Fbn1+/− corneas were significantly thinner than wild types and displayed a higher radius of curvature. In the Fbn1+/− corneas, elastic microfibril bundles were significantly reduced in density and disorganized compared to wild-type controls, in addition to containing a higher average center-to-center collagen interfibrillar spacing in the center of the cornea. No other differences were detected in stromal ultrastructure or proteoglycan distribution between the two groups. Proteoglycan side chains appeared to colocalize with the microfibril bundles. Conclusions: Elastic fibers have an important, multifunctional role in the cornea as highlighted by the differences observed between Fbn1+/− and wild type animals. We contend that the presence of normal quantities of structurally organized elastic fibers are required to maintain the correct geometry of the cornea, which is disrupted in Marfan syndrome

Leveraging eco-evolutionary models for gene drive risk assessment

Engineered gene drives create potential for both widespread benefits and irreversible harms to ecosystems. CRISPR-based systems of allelic conversion have rapidly accelerated gene drive research across diverse taxa, putting field trials and their necessary risk assessments on the horizon. Dynamic processbased models provide flexible quantitative platforms to predict gene drive outcomes in the context of system-specific ecological and evolutionary features. Here, we synthesize gene drive dynamic modeling studies to highlight research trends, knowledge gaps, and emergent principles, organized around their genetic, demographic, spatial, environmental, and implementation features. We identify the phenomena that most significantly influence model predictions, discuss limitations of biological complexity and uncertainty, and provide insights to promote responsible development and model-assisted risk assessment of gene drives. Supplemental files attached belo

A study of stromal riboflavin absorption inex vivoporcine corneas using new and existing delivery protocols for corneal cross-linking

Purpose: To indirectly measure stromal riboflavin penetration using commercially available riboflavin solutions and new and existing epithelium-off, trans-epithelial and iontophoresis-assisted delivery protocols. Methods: Forty porcine eyes were divided into eight groups. Group 1: Ricrolin applied to the de-epithelialised cornea for 30 min; Group 2: epithelium-intact, no treatment; Groups 3–5: epithelium-intact, 30-min application of Ricrolin TE, Mediocross TE or ParaCel/Vibex, respectively. Group 6: epithelium-intact, Ricrolin+ iontophoresis-assisted delivery for 5 min; Group 7: epithelium-intact, Ricrolin+ iontophoresis-assisted delivery for 5 min with a 20-min riboflavin soak; and Group 8: epithelium-intact, Ricrolin+ iontophoresis-assisted delivery for 5 min, 15-min soak and another 5 min of iontophoresis. After a saline wash, light transmission spectra were obtained from each cornea, before and after epithelial removal. Results: Corneas in groups 1 and 8 showed a distinct riboflavin absorption peak between 400 and 520 nm. The optical density of the corneas in groups 3–7 did not differ significantly from that of the untreated corneas (group 2). Conclusions: A modification to the standard iontophoresis trans-epithelial technique resulted in successful penetration of riboflavin into the stroma and appears to offer the most promise for epithelium-on cross-linking

Personalized practice dosages may improve motor learning in older adults compared to “standard of care” practice dosages: A randomized controlled trial

Standard dosages of motor practice in clinical physical rehabilitation are insufficient to optimize motor learning, particularly for older patients who often learn at a slower rate than younger patients. Personalized practice dosing (i.e., practicing a task to or beyond one's plateau in performance) may provide a clinically feasible method for determining a dose of practice that is both standardized and individualized, and may improve motor learning. The purpose of this study was to investigate whether personalized practice dosages [practice to plateau (PtP) and overpractice (OVP)] improve retention and transfer of a motor task, compared to low dose [LD] practice that mimics standard clinical dosages. In this pilot randomized controlled trial (NCT02898701, ClinicalTrials.gov), community-dwelling older adults (n = 41, 25 female, mean age 68.9 years) with a range of balance ability performed a standing serial reaction time task in which they stepped to specific targets. Presented stimuli included random sequences and a blinded repeating sequence. Participants were randomly assigned to one of three groups: LD (n = 15, 6 practice trials equaling 144 steps), PtP (n = 14, practice until reaching an estimated personal plateau in performance), or OVP (n = 12, practice 100% more trials after reaching an estimated plateau in performance). Measures of task-specific learning (i.e., faster speed on retention tests) and transfer of learning were performed after 2–4 days of no practice. Learning of the random sequence was greater for the OVP group compared to the LD group (p = 0.020). The OVP (p = 0.004) and PtP (p = 0.010) groups learned the repeated sequence more than the LD group, although the number of practice trials across groups more strongly predicted learning (p = 0.020) than did group assignment (OVP vs. PtP, p = 0.270). No group effect was observed for transfer, although significant transfer was observed in this study as a whole (p < 0.001). Overall, high and personalized dosages of postural training were well-tolerated by older adults, suggesting that this approach is clinically feasible. Practicing well-beyond standard dosages also improved motor learning. Further research should determine the clinical benefit of this personalized approach, and if one of the personalized approaches (PtP vs. OVP) is more beneficial than the other for older patients

Personalized practice dosages may improve motor learning in older adults compared to standard of care practice dosages: A randomized controlled trial

Standard dosages of motor practice in clinical physical rehabilitation are insufficient to optimize motor learning, particularly for older patients who often learn at a slower rate than younger patients. Personalized practice dosing (i.e., practicing a task to or beyond one\u27s plateau in performance) may provide a clinically feasible method for determining a dose of practice that is both standardized and individualized, and may improve motor learning. The purpose of this study was to investigate whether personalized practice dosages