Hyperbolastic growth models: theory and application

BACKGROUND: Mathematical models describing growth kinetics are very important for predicting many biological phenomena such as tumor volume, speed of disease progression, and determination of an optimal radiation and/or chemotherapy schedule. Growth models such as logistic, Gompertz, Richards, and Weibull have been extensively studied and applied to a wide range of medical and biological studies. We introduce a class of three and four parameter models called "hyperbolastic models" for accurately predicting and analyzing self-limited growth behavior that occurs e.g. in tumors. To illustrate the application and utility of these models and to gain a more complete understanding of them, we apply them to two sets of data considered in previously published literature. RESULTS: The results indicate that volumetric tumor growth follows the principle of hyperbolastic growth model type III, and in both applications at least one of the newly proposed models provides a better fit to the data than the classical models used for comparison. CONCLUSION: We have developed a new family of growth models that predict the volumetric growth behavior of multicellular tumor spheroids with a high degree of accuracy. We strongly believe that the family of hyperbolastic models can be a valuable predictive tool in many areas of biomedical and epidemiological research such as cancer or stem cell growth and infectious disease outbreaks

Evaluating Player Strategies in the Design of a Hot Hand Game

The user’s strategy and their approach to decisionmakingare two important concerns when designing user-centricsoftware. While decision-making and strategy are key factors in awide range of business systems from stock market trading tomedical diagnosis, in this paper we focus on the role these factorsplay in a serious computer game. Players may adopt individualstrategies when playing a computer game. Furthermore, differentapproaches to playing the game may impact on the effectivenessof the core mechanics designed into the game play. In this paperwe investigate player strategy in relation to two serious gamesdesigned for studying the ‘hot hand’. The ‘hot hand’ is aninteresting psychological phenomenon originally studied in sportssuch as basketball. The study of ‘hot hand’ promises to shedfurther light on cognitive decision-making tasks applicable todomains beyond sport. The ‘hot hand’ suggests that playerssometimes display above average performance, get on a hotstreak, or develop ‘hot hands’. Although this is a widely heldbelief, analysis of data in a number of sports has produced mixedfindings. While this lack of evidence may indicate belief in the hothand is a cognitive fallacy, alternate views have suggested thatthe player’s strategy, confidence, and risk-taking may accountfor the difficulty of measuring the hot hand. Unfortunately, it isdifficult to objectively measure and quantify the amount of risktaking in a sporting contest. Therefore to investigate thisphenomenon more closely we developed novel, tailor-madecomputer games that allow rigorous empirical study of ‘hothands’. The design of such games has some specific designrequirements. The gameplay needs to allow players to perform asequence of repeated challenges, where they either fail or succeedwith about equal likelihood. Importantly the design also needs toallow players to choose a strategy entailing more or less risk inresponse to their current performance. In this paper we comparetwo hot hand game designs by collecting empirical data thatcaptures player performance in terms of success and level ofdifficulty (as gauged by response time). We then use a variety ofanalytical and visualization techniques to study player strategiesin these games. This allows us to detect a key design flaw the firstgame and validate the design of the second game for use infurther studies of the hot hand phenomenon

Detecting injury risk factors with algorithmic models in elite women’s pathway cricket

This exploratory retrospective cohort analysis aimed to explore how algorithmic models may be able to identify important risk factors that may otherwise not have been apparent. Their association with injury was then assessed with more conventional data models. Participants were players registered on the England and Wales Cricket Board women’s international development pathway (n=17) from April 2018 to August 2019 aged between 14–23 years (mean 18.2±1.9) at the start of the study period. Two supervised learning techniques (a decision tree and random forest with traditional and conditional algorithms) and generalised linear mixed effect models explored associations between risk factors and injury. The supervised learning models did not predict injury (decision tree and random forest area under the curve [AUC] of 0.66 and 0.72 for conditional algorithms) but did identify important risk factors. The best-fitting generalised linear mixed effect model for predicting injury (Akaike Information Criteria [AIC]=843.94, conditional r-squared=0.58) contained smoothed differential 7-day load (P<0.001), average broad jump scores (P<0.001) and 20 m speed (P<0.001). Algorithmic models identified novel injury risk factors in this population, which can guide practice and future confirmatory studies can now investigate

Study of the magnetite to maghemite transition using microwave permittivity and permeability measurements

The microwave cavity perturbation (MCP) technique is used to identify the transition from magnetite (Fe3O4) to the meta-stable form of maghemite (γ-Fe2O3). In this study Fe3O4 was annealed at temperatures from 60 to 300 °C to vary the oxidation. Subsequent to annealing, the complex permittivity and magnetic permeability of the iron oxide powders were measured. The transition to γ-Fe2O3 was corroborated with x-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS) and vibrating sample magnetometry (VSM). XRD, XPS and VSM implied that the starting powder was consistent with Fe3O4 and the powders annealed at more than 200 °C were transitioning to γ-Fe2O3. The MCP measurements gave large differences in both complex permittivity and magnetic permeability of the two phases in the frequency range of 2.5–10.2 GHz. Magnetic permeability decreased with annealing temperature, though magnetic losses showed frequency dependent behaviour. Complex permittivity measurements showed a large decrease in both dielectric constant and losses at all measurement frequencies, as well as a prominent loss peak centred around the phase transition temperatures. We interpret the loss peak as being a consequence of field effects due to an intermediate multi-phase mixture. Additionally, almost no frequency dependence was observed. The reduction in complex permittivity implies that the $\text{Fe}_{\text{oct}}^{2+}$ cations in the lattice provide a significant contribution to polarization at microwave frequencies and the effects of $\text{Fe}_{\text{oct}}^{3+}$ are nominal in comparison. The change in loss can be explained as a combination of the differences in the effective conductivity of the two phases (i.e. Fe3O4 exhibits electron-hopping conduction whereas the presence of vacancies in γ-Fe2O3 nullifies this). This shows that the non-invasive MCP measurements serve as a highly sensitive and versatile method for looking at this phase transition in iron and potentially the effects of oxidation states on the polarization in other iron oxides

Effect of Atomoxetine Treatment on Reading and Phonological Skills in Children with Dyslexia or Attention-Deficit/Hyperactivity Disorder and Comorbid Dyslexia in a Randomized, Placebo-Controlled Trial

OBJECTIVES: Evaluated the effects of atomoxetine on the reading abilities of children with dyslexia only or attention-deficit/hyperactivity disorder (ADHD) and comorbid dyslexia. METHODS: Children aged 10-16 years (N = 209) met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for dyslexia only (n = 58), ADHD and comorbid dyslexia (n = 124), or ADHD only (n = 27) and were of normal intelligence. Patients were treated with atomoxetine (1.0-1.4 mg/kg/day) or placebo in a 16-week, randomized, placebo-controlled, double-blind trial. The dyslexia-only and ADHD and comorbid dyslexia groups were randomized 1:1; the ADHD-only group received atomoxetine in a blinded manner. Reading abilities were measured with the Woodcock Johnson III (WJIII), Comprehensive Test of Phonological Processing (CTOPP), Gray Oral Reading Tests-4, and Test of Word Reading Efficiency. RESULTS: Atomoxetine-treated dyslexia-only patients compared with placebo patients had significantly greater improvement (p < 0.02) with moderate to approaching high effect sizes (ES) on WJIII Word Attack (ES = 0.72), Basic Reading Skills (ES = 0.48), and Reading Vocabulary (ES = 0.73). In the atomoxetine-treated ADHD and comorbid dyslexia group, improvement on the CTOPP Elision measure (ES = 0.50) was significantly greater compared with placebo (p < 0.02). Total, inattentive, and hyperactive/impulsive ADHD symptom reductions were significant in the atomoxetine-treated ADHD and comorbid dyslexia group compared with placebo, and from baseline in the ADHD-only group (p ≤ 0.02). ADHD symptom improvements in the ADHD and comorbid dyslexia group were not correlated with improvements in reading. CONCLUSIONS: Atomoxetine treatment improved reading scores in patients with dyslexia only and ADHD and comorbid dyslexia. Improvements for patients with dyslexia only were in critical components of reading, including decoding and reading vocabulary. For patients with ADHD and comorbid dyslexia, improvements in reading scores were distinct from improvement in ADHD inattention symptoms alone. These data represent the first report of improvements in reading measures following pharmacotherapy treatment in patients with dyslexia only evaluated in a randomized, double-blind trial

Impedance spectroscopy characterization of neutron irradiated thermoelectric modules for space nuclear power

The European Space Agency is currently supporting the research and development of advanced radioisotope power systems utilising thermoelectric modules. The performance of thermoelectric modules following exposure to neutron radiation is of significant interest due to the likely application of radioisotope thermoelectric generators in deep space exploration or planetary landers requiring prolonged periods of operation. This study utilises impedance spectroscopy to characterise the effects of neutron irradiation on the performance of complete thermoelectric modules, as opposed to standalone material. For a 50 We americium-241 radioisotope thermoelectric generator design, it is estimated that the TE modules could be exposed to a total integrated flux of approximately 5 × 1013 neutrons cm-2 (>1 MeV). In this study, an equivalent neutron dose was simulated experimentally via an acute 2-hour exposure in a research pool reactor. Bi2Te3-based thermoelectric modules with different leg aspect ratios and microstructures were investigated. Gamma-ray spectroscopy was initially used to identify activated radionuclides and hence quantify irradiation induced transmutation doping. To evaluate the thermoelectric properties pre- and post-irradiation, impedance spectroscopy characterization was employed. Isochronal thermal annealing of defects imparted by the irradiation process, revealed that polycrystalline based modules required significantly higher temperature than those with a monolithic microstructure. Whilst this may indicate a greater susceptibility to neutron irradiation, all tested modules demonstrated sufficient radiation hardness for use within an americium-241 radioisotope thermoelectric generator. Furthermore, the work reported demonstrates that impedance spectroscopy is a highly capably diagnostic tool for characterising the in-service degradation of complete thermoelectric devices

Injuries in England and Wales Elite Men’s Domestic Cricket:A nine season review from 2010 to 2018

Objectives: This study primarily aimed to explore injury incidence rates in the three main domestic competition formats in England and Wales (First-Class, One-Day and Twenty20 [T20]). For the first time, the study also describes the epidemiology of elite men's domestic cricket injuries across nine seasons (2010–2018 inclusive). Design: Prospective cohort analysis. Methods: Injury incidence and prevalence from all injuries calculated according to the updated international consensus statement on injury surveillance in cricket, with statistical process control charts (SPC) used to detect trends in the data. Results: The average match injury incidence was 102 injuries/1000 days of play, with highest incidence in One-Day (254 injuries/1000 days of play), followed by T20 (136 injuries/1000 days of play) and First-Class Cricket (68 injuries/1000 days of play). Most match injuries were sustained during bowling (41.6 injuries/1000 days of play), followed by fielding (26.8 injuries/1000 days of play) and batting (22.3 injuries/1000 days of play). The thigh was the body area most commonly injured (7.4 injuries/100 players per season), with lumbar spine injuries the most prevalent (1.3% of players unavailable on any given day during the season). On average, 7.5% of players were unavailable on any given day during the domestic season when all injuries were considered (match and training). The SPC charts showed relatively consistent match injury incidence for all competitions, reproduced across all nine seasons. Conclusion: These findings provide a robust empirical base for the extent of the injury problem in domestic cricket played in England and Wales, with similar injury profiles across the three formats.</p

Structural basis for activation of calcineurin by calmodulin

The highly conserved phosphatase calcineurin plays vital roles in numerous processes including T-cell activation, development and function of the central nervous system, and cardiac growth. It is activated by the calcium sensor calmodulin. Calmodulin binds to a regulatory domain within calcineurin, causing a conformational change that displaces an autoinhibitory domain from the active site, resulting in activation of the phosphatase. This is the same general mechanism by which calmodulin activates calmodulin-dependent protein kinases. Previously published data has hinted that the regulatory domain of calcineurin is intrinsically disordered. In this work we demonstrate that the regulatory domain is unstructured and that it folds upon binding calmodulin, ousting the autoinhibitory domain from the catalytic site. The regulatory domain is 95 residues long, with the autoinhibitory domain attached to its C-terminal end and the 24 residue calmodulin binding region towards the N-terminal end. This is unlike the calmodulin-dependent protein kinases which have calmodulin binding sites and autoinhibitory domains immediately adjacent in sequence. Our data demonstrate that not only does the calmodulin binding region fold, but that an ~25-30 residue region between it and the autoinhibitory domain also folds, resulting in over half of the regulatory domain adopting α-helical structure. This appears to be the first observation of calmodulin inducing folding of this scale outside of its binding site on a target protein

Structural Basis for Activation of Calcineurin by Calmodulin

The highly conserved phosphatase calcineurin (CaN) plays vital roles in numerous processes including T-cell activation, development and function of the central nervous system, and cardiac growth. It is activated by the calcium sensor calmodulin (CaM). CaM binds to a regulatory domain (RD) within CaN, causing a conformational change that displaces an autoinhibitory domain (AID) from the active site, resulting in activation of the phosphatase. This is the same general mechanism by which CaM activates CaM-dependent protein kinases. Previously published data have hinted that the RD of CaN is intrinsically disordered. In this work, we demonstrate that the RD is unstructured and that it folds upon binding CaM, ousting the AID from the catalytic site. The RD is 95 residues long, with the AID attached to its C-terminal end and the 24-residue CaM binding region toward the N-terminal end. This is unlike the CaM-dependent protein kinases that have CaM binding sites and AIDs immediately adjacent in sequence. Our data demonstrate that not only does the CaM binding region folds but also an ∼25- to 30-residue region between it and the AID folds, resulting in over half of the RD adopting α-helical structure. This appears to be the first observation of CaM inducing folding of this scale outside of its binding site on a target protein

Biological Invasions: Recommendations for U.S. Policy and Management

The Ecological Society of America has evaluated current U.S. national policies and practices on biological invasions in light of current scientific knowledge. Invasions by harmful nonnative species are increasing in number and area affected; the damages to ecosystems, economic activity, and human welfare are accumulating. Without improved strategies based on recent scientific advances and increased investments to counter invasions, harm from invasive species is likely to accelerate. Federal leadership, with the cooperation of state and local governments, is required to increase the effectiveness of prevention of invasions, detect and respond quickly to new potentially harmful invasions, control and slow the spread of existing invasions, and provide a national center to ensure that these efforts are coordinated and cost effective. Specifically, the Ecological Society of America recommends that the federal government take the following six actions: (1) Use new information and practices to better manage commercial and other pathways to reduce the transport and release of potentially harmful species; (2) Adopt more quantitative procedures for risk analysis and apply them to every species proposed for importation into the country; (3) Use new cost-effective diagnostic technologies to increase active surveillance and sharing of information about invasive species so that responses to new invasions can be more rapid and effective; (4) Create new legal authority and provide emergency funding to support rapid responses to emerging invasions; (5) Provide funding and incentives for cost-effective programs to slow the spread of existing invasive species in order to protect still uninvaded ecosystems, social and industrial infrastructure, and human welfare; and (6) Establish a National Center for Invasive Species Management (under the existing National Invasive Species Council) to coordinate and lead improvements in federal, state, and international policies on invasive species. Recent scientific and technical advances provide a sound basis for more cost-effective national responses to invasive species. Greater investments in improved technology and management practices would be more than repaid by reduced damages from current and future invasive species. The Ecological Society of America is committed to assist all levels of government and provide scientific advice to improve all aspects of invasive-species management