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The task for an embodied cognitive understanding of humans' actions with tools is to elucidate how the human body, as a whole, supports the perception of affordances and dexterous action with objects in relation to other objects. Here, we focus on the relationship between humans' actions with handheld tools and bipedal posture. Posture plays a pivotal role in shaping animals' perception and action dynamics. While humans stand and locomote bipedally, other primates predominantly employ quadrupedal postures and locomotion, relying on both hands and feet to support the body. Drawing upon evidence from evolutionary biology, developmental psychology and performance studies, we elucidate the influence of bipedalism on our actions with objects and on our proficiency in using tools. We use the metaphor of cascades to capture the dynamic, nonlinear transformations in morphology and behaviour associated with posture and the use of tools across evolutionary and developmental timescales. Recent work illustrates the promise of multifractal cascade analysis to reveal nonlinear, cross-scale interactions across the entire body in real-time, supporting the perception of affordances for actions with tools. Cascade analysis enriches our comprehension of real-time performance and facilitates exploration of the relationships among whole-body coordination, individual development, and evolutionary processes. This article is part of the theme issue 'Minds in movement: embodied cognition in the age of artificial intelligence'. [ABSTRACT FROM AUTHOR]

The Jurassic/Cretaceous transition was characterized by several distinct palaeoenvironmental processes and events, amongst which some of the best known are the late Tithonian–early Berriasian aridization and the late Berriasian tectonic reactivation in the Neotethyan Collision Belt. This study aims to reconstruct the latest Jurassic–earliest Cretaceous palaeoenvironment and its evolution in the area of the Transdanubian Range (Hárskút and Lókút successions, Hungary), and provide new data on the relation between climate changes, palaeoceanography and marine ecosystems. Herein, calcareous nannofossil and geochemical data are presented and put into a geochronological framework in order to evaluate and compare palaeoenvironmental signals recorded in the two studied successions; the resultant scenario is compared with published literature data from both the western Tethyan region and northern Europe. Accordingly, in the Transdanubian Range, the relatively humid climate of the early Tithonian was followed by the late Tithonian–early Berriasian arid phase and the late Berriasian humidification. Besides, two intervals of palaeoceanographic perturbations were documented in the upper Tithonian–lowermost Berriasian (OD I), and the lower/upper Berriasian transition beds (OD II); these are manifested by the record of seafloor hypoxia and elevated accumulations of micronutrients, as well as changes in calcareous nannofossil assemblages. In the view of this study, the most probable trigger of the late Tithonian–early Berriasian aridization was a restriction in the atmospheric circulation (including monsoons), which was forced by climate cooling and lowering thermal gradient between landmasses and the ocean. Under such conditions, the mechanism of a wind‐induced water mixing might become less efficient, driving seawater stratification, seafloor hypoxia and increased burial of nutrients. Although the humid climate of the late Berriasian likely resumed the monsoon‐type circulation, the tectonic reactivation and uplift in the NeoTethyan Collision Belt might have effectively separated the Bakony Basin from the ‘open’ NeoTethys, which hampered the marine circulation and efficient water mixing in the former. [ABSTRACT FROM AUTHOR]

A rich and complex temporal structure of variability in postural sway characterizes healthy and adaptable postural control. However, neurodegenerative disorders such as Parkinson's disease, which often manifest as tremors, rigidity, and bradykinesia, disrupt this healthy variability. This study examined postural sway in young and older adults, including individuals with Parkinson's disease, under different upright standing conditions to investigate the potential connection between the temporal structure of variability in postural sway and Parkinsonism. A novel and innovative method called oriented fractal scaling component analysis was employed. This method involves decomposing the two-dimensional center of pressure (CoP) planar trajectories to pinpoint the directions associated with minimal and maximal temporal correlations in postural sway. As a result, it facilitates a comprehensive assessment of the directional characteristics within the temporal structure of sway variability. The results demonstrated that healthy young adults control posture along two orthogonal directions closely aligned with the traditional anatomical anteroposterior (AP) and mediolateral (ML) axes. In contrast, older adults and individuals with Parkinson's disease controlled posture along suborthogonal directions that significantly deviate from the AP and ML axes. These findings suggest that the altered temporal structure of sway variability is evident in individuals with Parkinson's disease and underlies postural deficits, surpassing what can be explained solely by the natural aging process. [ABSTRACT FROM AUTHOR]

Walking exhibits stride-to-stride variations. Given ongoing perturbations, these variations critically support continuous adaptations between the goal-directed organism and its surroundings. Here, we report that stride-to-stride variations during self-paced overground walking show cascade-like intermittency—stride intervals become uneven because stride intervals of different sizes interact and do not simply balance each other. Moreover, even when synchronizing footfalls with visual cues with variable timing of presentation, asynchrony in the timings of the cue and footfall shows cascade-like intermittency. This evidence conflicts with theories about the sensorimotor control of walking, according to which internal predictive models correct asynchrony in the timings of the cue and footfall from one stride to the next on crossing thresholds leading to the risk of falling. Hence, models of the sensorimotor control of walking must account for stride-to-stride variations beyond the constraints of threshold-dependent predictive internal models. [ABSTRACT FROM AUTHOR]

The creativity and emergence of biological and psychological behavior tend to be nonlinear, and correspondingly, biological and psychological measures contain degrees of irregularity. The linear model might fail to reduce these measurements to a sum of independent random factors (yielding a stable mean for the measurement), implying nonlinear changes over time. The present work reviews some of the concepts implicated in nonlinear changes over time and details the mathematical steps involved in their identification. It introduces multifractality as a mathematical framework helpful in determining whether and to what degree the measured series exhibits nonlinear changes over time. These mathematical steps include multifractal analysis and surrogate data production for resolving when multifractality entails nonlinear changes over time. Ultimately, when measurements fail to fit the structures of the traditional linear model, multifractal modeling allows for making those nonlinear excursions explicit, that is, to come up with a quantitative estimate of how strongly events may interact across timescales. This estimate may serve some interests as merely a potentially statistically significant indicator of independence failing to hold, but we suspect that this estimate might serve more generally as a predictor of perceptuomotor or cognitive performance. [ABSTRACT FROM AUTHOR]

An adaptive response to unexpected perturbations requires near-term and long-term adjustments over time. We used multifractal analysis to test how nonlinear interactions across timescales might support an adaptive response following an unpredictable perturbation. We reanalyzed torque data from 44 young and 24 older adults who performed a single-leg squat task challenged by an unexpected mechanical perturbation and a secondary visual-cognitive task. We report three findings: (a) multifractal nonlinearity interacted with pre-perturbation torque production and task error to presage greater pre-voluntary feedforward increases and greater voluntary reductions, respectively, in post-perturbation task error; (b) multifractal nonlinearity presaged relatively smaller task error than standard deviations of both pre-perturbation torques and pre-perturbation task error; and (c) increased task demand (e.g., age-related changes in dexterity and dual-task settings) led to multifractal nonlinearity presaging reduced task error. All these results were consistent with our expectations, except that a pre-perturbation knee torque-dependent increase in post-perturbation task error appeared later for older than for younger participants. This correlational multifractal modeling offered theoretical clarity on the possible roles of nonlinear interactions across timescales, moderating both feedforward and feedback processes, and presaging greater stability when the standard deviation is relatively large and task demands are strong. Thus, multifractal nonlinearity usefully describes movement variability even when paired with classical descriptors like the standard deviation. We discuss potential insights from these findings for understanding suprapostural dexterity and developing rehabilitative interventions. [ABSTRACT FROM AUTHOR]

Testosterone is a powerful steroid hormone that can impact the brain and behavior in various ways, including regulating behavioral and neuroendocrine (hypothalamic-pituitary-adrenal (HPA) axis) stress responses. Early in life androgens can act to alter development of brain regions associated with stress regulation, which ultimately impacts the display of stress responses later in life. Adult circulating androgens can also influence the expression of distinct genes and proteins that regulate stress responses. These changes in the brain are hypothesized to underlie the potent effects of androgens in regulating behaviors related to stress and stress-induced activation of the HPA axis. Androgens can induce alterations in these functions through direct binding to the androgen receptor (AR) or following conversion to estrogens and subsequent binding to estrogen receptors including estrogen receptor alpha (ERα), beta (ERβ), and G protein-coupled estrogen receptor 1 (GPER1). In this review, we focus on the role of androgens in regulating behavioral and neuroendocrine stress responses at different stages of the lifespan and the sex hormone receptors involved in regulating these effects. We also review the specific brain regions and cell phenotypes upon which androgens are proposed to act to regulate stress responses with an emphasis on hypothalamic and extended amygdala subregions. This knowledge of androgen effects on these neural systems is critical for understanding how sex hormones regulate stress responses. • Androgens potently regulate behavioral and neuroendocrine stress responses. • Effects of androgens differ depending on timing of exposure (development versus adult). • Androgens can modulate stress functions through various sex hormone receptors. • Various brain areas and cell types are discussed as sites for androgen regulation of stress responses. [ABSTRACT FROM AUTHOR]

• Ergodicity implies that mean response of samples represents individuals of samples. • Evidence in these fields indicates systematic violations of the ergodic assumption. • This violation hampers scientific progress. • We propose using statistical measures that can themselves encode nonergodicity. • This step will lead to a paradigm shift in biological and psychological sciences. Modern biomedical, behavioral and psychological inference about cause-effect relationships respects an ergodic assumption, that is, that mean response of representative samples allow predictions about individual members of those samples. Recent empirical evidence in all of the same fields indicates systematic violations of the ergodic assumption. Indeed, violation of ergodicity in biomedical, behavioral and psychological causes is precisely the inspiration behind our research inquiry. Here, we review the long term costs to scientific progress in these domains and a practical way forward. Specifically, we advocate using statistical measures that can themselves encode the degree and type of nonergodicity in measurements. Taking such steps will lead to a paradigm shift, allowing researchers to investigate the nonstationary, far-from-equilibrium processes that characterize the creativity and emergence of biological and psychological behavior. [ABSTRACT FROM AUTHOR]

An enduring controversy in biological and psychological sciences has centered on the tension between the role of random multiplicative cascade processes and the sometimes independent, additive effects of seemingly modular, scale-dependent component processes. The former supports the fluid interactivity of an organism's faculties for perception, action, and cognition, and the latter entails a set of constraints over and across which the interactivity may unfold. These random multiplicative cascades embody nonlinear phenomena wherein structures repeatedly divide, branch, or aggregate across successive generations, giving rise to multiplicative interactions spanning various space and time scales. We examined the impact of introducing additivity within an array of multiplicative interactions among component processes. Our findings reveal that additivity suppresses the multifractal nonlinearity engendered by multiplicative cascade dynamics. This discovery carries profound implications. Theoretically, it underscores the significance of multiplicative interactions in producing multifractality within empirical time series. At an operational level, it suggests that systems undergoing simplification due to factors such as disease or adaptive strategies may temporarily cultivate additivity to dampen the multifractality arising from multiplicative interactions among constituent components. We advocate for further exploration into the roles of additive and multiplicative interactions in understanding and facilitating multifractal support for the adaptive use of perception, action, and cognition. • Ongoing research unveils how random multiplicative cascades underpin an organism's cognitive abilities. • Multiplicative cascade processes generate nonlinear interactions across generations, spanning various scales. • Past work highlights that multifractality nonlinearity stems from multiplicative interactions, not additive ones. • New findings suggest that introducing additivity suppresses multifractal nonlinearity. • This discovery has profound implications for understanding adaptive behaviors and empirical time series. [ABSTRACT FROM AUTHOR]

Estradiol and testosterone are powerful steroid hormones that impact brain function in numerous ways. During development, these hormones can act to program the adult brain in a male or female direction. During adulthood, gonadal steroid hormones can activate or inhibit brain regions to modulate adult functions. Sex differences in behavioral and neuroendocrine (i.e., hypothalamic pituitary adrenal (HPA) axis) responses to stress arise as a result of these organizational and activational actions. The sex differences that are present in the HPA and behavioral responses to stress are particularly important considering their role in maintaining homeostasis. Furthermore, dysregulation of these systems can underlie the sex biases in risk for complex, stress-related diseases that are found in humans. Although many studies have explored the role of estrogen and estrogen receptors in mediating sex differences in stress-related behaviors and HPA function, much less consideration has been given to the role of androgens. While circulating androgens can act by binding and activating androgen receptors, they can also act by metabolism to estrogenic molecules to impact estrogen signaling in the brain and periphery. This review focuses on androgens as an important hormone for modulating the HPA axis and behaviors throughout life and for setting up sex differences in key stress regulatory systems that could impact risk for disease in adulthood. In particular, impacts of androgens on neuropeptide systems known to play key roles in HPA and behavioral responses to stress (corticotropin-releasing factor, vasopressin, and oxytocin) are discussed. A greater knowledge of androgen action in the brain is key to understanding the neurobiology of stress in both sexes. [ABSTRACT FROM AUTHOR]

The reproduction of the sea urchin Pseudechinus magellanicus and the influence of environmental factors were studied during a 27-month period in central Patagonia, Argentina, where this species is among the dominant grazers in kelp forests and tide pools. The monthly variation in the gonad dry weights, gonadal stages and other quantitative reproductive variables (oocyte diameter, density and thickness of spermatogenic columns) indicated a clearly annual gametogenic cycle and revealed a high level of spawning synchrony. A main spawning event occurs between August and September, and a minor and asynchronous spawning event was recorded during the austral summer (January–March). The highest gonadal growth rate occurs between late spring and summer, accompanied by growth and early prematurity gonadal stages, indicating active vitellogenesis. The accumulation of ova begins in autumn and shows a peak during winter. After spawning, the recovery stages are not extended in time and ovaries do not show a complete meshwork of nutritive phagocytes within the acinus, suggesting simultaneous reabsorption and inversion processes. Spermatogenesis shows a higher maturation rate than oogenesis, and a higher temporal prevalence of premature and mature stages. Major spawning coincides with the first rise in seawater temperature, the maximum rate of increase in day length and the maximum peak of chlorophyll a. Results also revealed some temporal differences in the gonadal cycle, vitellogenesis and spawning periods compared with other P. magellanicus populations from different latitudes. This could be attributed to individual differences in the acquisition and allocation of energy for gametogenesis, as well as to local environmental factors. [ABSTRACT FROM AUTHOR]

One of the mechanisms responsible for blood pressure (BP) regulation is thought to be oxidative stress. In this review, we highlight preclinical studies that strongly support a role for oxidative stress in development and maintenance of hypertension in male animals, based on depressor responses to antioxidants, particularly tempol and apocynin. In females, oxidative stress seems to be important in the initial development of hypertension. However, whether maintenance of hypertension in females is mediated by oxidative stress is not clear. In clinical studies, pharmacological intervention to reduce BP with antioxidants has conflicting results, mostly negative. This review will discuss the uncertainties regarding blood pressure control and oxidative stress and potential reasons for these outcomes. [ABSTRACT FROM AUTHOR]

The present work is a reanalysis of prior work documenting postural sway in phasmids (i.e., “stick insects”) []. The prior work pursued the possibility that postural sway was an evolutionary adaptation supporting motion camouflage to avoid the attention of predators. For instance, swaying along with leaves blown by the wind might reduce the likelihood of standing out to a predator. The present work addresses the alternative—but by no means conflicting and perhaps more explanatory—proposal that phasmid postural sway carries evidence of the tensegrity-like structures allowing postural stabilization under wind-like stimulation. Tensegrity structures are prestressed architectures embodying nonlinear interactions across scales of space and time that provide context-sensitive responses faster than neural tissue can support. Multifractal modeling of the postural-displacement series initially recorded in [] offers a metric equally effective for quantifying complexity of phasmid postural sway under wind stimulation as for quantifying complexity of human postural sway [–]. Furthermore, multifractal modeling offers a means to demonstrate empirically the nonlinear interactions across space and time scales in body-wide coordination that tensegrity-based hypotheses predict. Specifically, multifractal modeling allows diagnosing the strength and direction of nonlinear interactions across time scale as the difference between multifractal estimates for the original postural-displacement series and for a sample of best-fitting linear models of the series. The reduction of postural sway directly following the application of wind stimulus appears as a significant decrease in the multifractal structure for original postural-displacement series as compared to best-fitting linear models of those series. This decrease indicates the capacity for nonlinear interactions across time scale to constrict variability, which is an aspect of nonlinear dynamics often overshadowed by the possibility that nonlinearity can produce more variability. This work offers the longer-range opportunity that multifractal modeling could provide a common language within which to coordinate behavioral sciences across a wide range of species. [ABSTRACT FROM AUTHOR]

The dominant assumption about the causal architecture of the mind is, that it is composed of a stable set of components that contribute independently to relevant observables that are employed to measure cognitive activity. This view has been called component-dominant dynamics. An alternative has been proposed, according to which the different components are not independent, but fundamentally interdependent, and are not stable basic properties of the mind, but rather an emergent feature of the mind given a particular task context. This view has been called interaction-dominant dynamics. In this paper, we review evidence for interaction-dominant dynamics as the causal architecture of the mind. We point out, that such an architecture is consistent with problems of convergence in research on the level of results and theorizing. Moreover, we point out that if interaction-dominant dynamics as the causal architecture of the mind were to be true, this would naturally lead to (some degree of) problems with generalization and replicability in sciences of the mind and brain, and would probably warrant changes in the scientific practice with regard to study-design and data analysis. [ABSTRACT FROM AUTHOR]

Prosody is the pattern of inflection, pitch, and intensity that communicates emotional meaning above and beyond the individual meanings of lexical items and gestures during spoken language. Research has often addressed prosody extending most clearly across multiple speech chunks and carrying properties specific to individual speakers and individual intents. However, prosody exerts effects on intended meaning even for relatively brief speech streams with minimal syntactic cues. The present work seeks to test whether prosody may actually clarify the intended meaning of a two-word phrase even when the basic phonemic sequence of the words is distorted. Thirty-eight undergraduate participants attempted to correctly categorize auditorily presented two-word phrases as belonging to one of three categories: nonsensical phrases; sensible phrases; and spoonerisms. Mixed Poisson modeling of cumulative accuracy found a significant positive interaction of prosody with phrase type indicating that conversational prosody made participants 8.27% more likely to accurately detect spoonerisms. Prosody makes spoken-language comprehension of two-word phrases more robust to distortions of phonemic sequence. [ABSTRACT FROM AUTHOR]

Context effects are ubiquitous in speech perception and reflect the ability of human listeners to successfully perceive highly variable speech signals. In the study of how listeners compensate for coarticulatory variability, past studies have used similar effects speech and tone analogues of speech as strong support for speech-neutral, general auditory mechanisms for compensation for coarticulation. In this manuscript, we revisit compensation for coarticulation by replacing standard button-press responses with mouse-tracking responses and examining both standard geometric measures of uncertainty as well as newer information-theoretic measures that separate fast from slow mouse movements. We found that when our analyses were restricted to end-state responses, tones and speech contexts appeared to produce similar effects. However, a more detailed time-course analysis revealed systematic differences between speech and tone contexts such that listeners’ responses to speech contexts, but not to tone contexts, changed across the experimental session. Analyses of the time course of effects within trials using mouse tracking indicated that speech contexts elicited fewer x-position flips but more area under the curve (AUC) and maximum deviation (MD), and they did so in the slower portions of mouse-tracking movements. Our results indicate critical differences between the time course of speech and nonspeech context effects and that general auditory explanations, motivated by their apparent similarity, be reexamined. [ABSTRACT FROM AUTHOR]

Natural samples containing tetrahedrite-tennantite, bournonite-seligmannite and geocronite-jordanite from the Coranda-Hondol ore deposit, Romania, were investigated by Raman spectroscopy to determine its capability to provide estimates of solid solutions in three common and widespread sulfosalt mineral series. Raman measurements were performed on extended solid solution series (Td1 to Td97, Bnn25 to Bnn93 and Gcn24 to Gcn67, apfu). The tetrahedrite-tennantite and bournonite-seligmannite solid solution series show strong correlations between spectroscopic parameters (position, relative intensity and shape of the Raman bands) and the Sb/(Sb+As) content ratio, while Raman spectra of geocronite-jordanite shows no evolution of Raman bands. In order to simplify the method used to estimate the Sb/(Sb+As) content ratio in tetrahedrite-tennantite and bournonite-seligmannite series, several linear equations of the first-order polynomial fit were obtained. The results are in good agreement with electron microprobe data. Moreover, a computer program was developed as an analytical tool for a fast and accurate determination of Sb/(Sb+As) content ratio by at least one spectroscopic parameter. These results indicate that Raman spectroscopy can provide direct information on the composition and structure of the tetrahedrite-tennantite and bournonite-seligmannite series. [ABSTRACT FROM AUTHOR]

Accounts of speech perception disagree on how listeners demonstrate perceptual constancy despite considerable variation in the speech signal due to speakers' coarticulation. According to the spectral contrast account, listeners' compensation for coarticulation (CfC) results from listeners perceiving the target-segment frequencies differently depending on the contrastive effects exerted by the preceding sound's frequencies. In this study, we reexamine a notable finding that listeners apparently demonstrate perceptual adjustments to coarticulation even when the identity of the speaker (i.e., the "source") changes midway between speech segments. We evaluated these apparent across-talker CfC effects on the rationale that such adjustments to coarticulation would likely be maladaptive for perceiving speech in multi-talker settings. In addition, we evaluated whether such cross-talker adaptations, if detected, were modulated by prior experience. We did so by manipulating the exposure phase of three groups of listeners by (a) merely exposing them to our stimuli (b) explicitly alerting them to talker change or (c) implicitly alerting them to this change. All groups then completed identical test blocks in which we assessed their CfC patterns in within- and across-talker conditions. Our results uniformly demonstrated that, while all three groups showed robust CfC shifts in the within-talker conditions, no such shifts were detected in the across-talker condition. Our results call into question a speaker-neutral explanation for CfC. Broadly, this demonstrates the need to carefully examine the perceptual demands placed on listeners in constrained experimental tasks and to evaluate whether the accounts that derive from such settings scale up to the demands of real-world listening. [ABSTRACT FROM AUTHOR]

Background Studies are required that evaluate real-world outcomes of inhaled aztreonam lysine in patients with cystic fibrosis (CF). Methods Our treatment-evaluator tool assessed the effectiveness of inhaled aztreonam in routine practice in 117 CF patients across four time periods (6–12 (P2) and 0–6 months (P1) pre-initiation, and 0–6 (T1) and 6–12 months (T2) post-initiation). Outcomes were: changes in %-predicted forced expiratory volume in 1 s (FEV 1 ), body-mass index (BMI), hospitalisation days and intravenous antibiotic usage. Results Median FEV 1 % predicted for each 6-month period was 38.9%, 34.6%, 37.1% and 36.5%; median change was − 2.0% between P2 and P1, increasing to + 0.6% (p < 0.001) between P1 and T1. Annualised hospital bed-days was reduced (p = 0.05) post-initiation, as was intravenous antibiotics days (p = 0.001). BMI increased over 6 months post-initiation (p ≤ 0.001). Conclusions In patients with CF in routine practice, inhaled aztreonam lysine is associated with improved lung function and weight, and reduced hospitalisation and intravenous antibiotic use. [ABSTRACT FROM AUTHOR]

This article addresses the still popular but incorrect idea that monofractal (sometimes called “fractal” for short) structure might be adefinitivesignature of nonlinearity and, as a corollary, that monofractal analyses are nonlinear analyses. That this point (i.e., “fractal = nonlinear”) is incorrect remains novel to many readers. We suspect that unfamiliarity with autocorrelation has helped eclipse the linearity of fractal structure from more popular appreciation. In this article, in order to explain the linear nature of monofractality and its difference from multifractality, we present an introduction to the autocorrelation function and review short-lag memory, nonstationary motions, and the intermediary set of fractionally integrated processes that conventional fractal analyses quantify. Understanding from our own experiences how surprising the linearity of fractals is to accept, we attempt to make our points clear with as much graphic depiction as math. We hope to share our own experiences in struggling with this potentially strange-sounding idea that, really, monofractals are linear while at the same time contrasting them to multifractals that can indicate nonlinearity. [ABSTRACT FROM PUBLISHER]

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects reproductive-age women. Hyperandrogenemia is present in a significant fraction (~80%) of women with PCOS. Increased prevalence of cardiometabolic risk factors is frequently observed in PCOS women. The present review aims to highlight the key role of androgens in mediating the negative cardiometabolic profile observed in PCOS women. [ABSTRACT FROM AUTHOR]

Pharmacoepidemiology studies are increasingly used for research into safe prescribing in chronic kidney disease (CKD). Typically, patients prescribed a drug are compared with patients who are not on the drug and outcomes are compared to draw conclusions about the drug effects. This review article aims to provide the reader with a framework to critically appraise such research. A key concern in pharmacoepidemiology studies is confounding, in that patients who have worse health status are prescribed more drugs or different agents and their worse outcomes are attributed to the drugs not the health status. It may be challenging to adjust for this using statistical methods unless a comparison group with a similar health status but who are prescribed a different (comparison) drug(s) is identified. Another challenge in pharmacoepidemiology is outcome misclassification, as people who are more ill engage more often with the health service, leading to earlier diagnosis in people who are frequent attenders. Finally, using replication cohorts with the same methodology in the same type of health system does not ensure that findings are more robust. We use two recent papers that investigated the association of proton pump inhibitor drugs with CKD as a device to review the main pitfalls of pharmacoepidemiology studies and how to attempt to mitigate against potential biases that can occur. [ABSTRACT FROM AUTHOR]

Interference between a walking task (target speeds on a self-paced treadmill) and dual visual and tactile-visual response time task was investigated. Ambulatory dual-task scenarios reveal how attention is divided between walking and additional tasks, but the impact of walking speed and dual-task modality on gait characteristics and dual-task performance is unclear. The purpose of this study was to evaluate the effect of visual and tactile-visual dual-task on gait performance. Participants (n=15) targeted four speeds (0.5, 1.0, 1.3, and 1.5 m/s) on a self-paced treadmill with a visual speed indicator (a green region centered at the target speed). Participants completed the same speed profile on the treadmill without (Self-Paced) and with a response time dual task (Self-Paced with Dual Task) requiring finger-tap responses to go/no-go cues. Six gait characteristics were calculated: proportion of time in the desired speed green region (GTP), speed ratio (ratio of mean to target speed), time to green region after target speed change (NRT), normalized stride width (NSW), normalized stride length (NSL), and stride time (ST). Both stride length and width were normalized by participant leg length. Lower GTP and greater speed ratio at slower speeds during dual tasking indicate speed-dependent changes in gait characteristics. Changes in NSL and ST were more affected by speed than dual task. These findings support that when speed is a parameter that is tracked, participants do not universally decrease speed in the presence of a dual task. These findings can support the decisions made when designing new wearable technologies that support navigation, communication, and mobility. • Participants quickly learned to achieve target speeds with a self-paced treadmill. • Walking at or near a preferred walking speed required fewer cognitive resources. • Presence of a dual task did not lead to a universal slowing of gait speed when a speed prompt was present. [ABSTRACT FROM AUTHOR]

Biological and psychological processes routinely break ergodicity, meaning they fail to have stable means (M e a n) and independent variation over time that we might find in additive white Gaussian noise (awGn). One possible reason for this failure of ergodicity is the failure of biological and psychological processes to exhibit independence across time. Multifractal evidence has long suggested that biological and psychological processes show strong signatures of nonlinear interactions across scales. These cross-scale interactions sooner befit a cascade-dynamical process than awGn. The present work thus compares awGn to simulations of multiplicative binomial cascades, submitting both types of series and shuffled versions of each to the Thirumalai-Mountain method for estimating ergodicity breaking. Estimating ergodicity breaking for original awGn and cascade series allows us to examine the sources of ergodicity breaking across the sequence, e.g., in temporal correlations specifying nonlinear interactions across scales, and examining ergodicity breaking of the shuffled series allows us to assess the raw, sequence-independent contribution of distributional properties (e.g., the heavy tails of a cascade) without the original temporal sequence. Raw cascade fluctuations and the standard deviation (S D) and root mean square (R M S) series describing those raw fluctuations break ergodicity, but nonlinear, cascade-dynamical descriptors: multifractal spectrum width (Δ α) and multifractal nonlinearity (t M F), maintain ergodicity. Interestingly, the fundamentally linear descriptor, fractal Hurst exponent (H f G n) shows moderate ergodicity breaking when describing the fundamentally nonlinear cascade processes, but the linear descriptor coefficient of variation (C V) controls for multiplicative relationships between S D and M e a n and maintains ergodicity. We conclude that the ergodicity of statistical descriptors depends on how well they can portray nonlinearity (Δ α and t M F) or at least multiplicativity (C V) of the underlying cascade processes. • Cascades are a potential source of non-ergodicity in biological and psychological measurements. • We simulated multiplicative binomial cascades that break ergodicity. • We examined the ergodic behavior of linear statistical descriptors of cascades. • We examined the ergodic behavior of fractal and multifractal descriptors of cascades. • Unlike linear statistical descriptors, multifractal descriptors provided ergodic characterization of cascade processes. [ABSTRACT FROM AUTHOR]

Systematically varied pyrylium and thiopyrylium photo-oxidants have been evaluated in the metal-free ring-opening-metathesis polymerization (MF-ROMP) of norbornene. Across the series, we observed higher conversion into polynorbornene from thiopyrylium species in comparison with pyrylium salts that were otherwise similarly functionalized. Additionally, more electron-rich photo-oxidants (i.e., weaker oxidants) correlated with higher conversions. [ABSTRACT FROM AUTHOR]

The brain might be exposed to irradiation under a variety of situations, including clinical treatments, nuclear accidents, dirty bomb scenarios, and military and space missions. Correctly recalling tasks learned prior to irradiation is important but little is known about post-learning effects of irradiation. It is not clear whether exposure to X-ray irradiation during memory consolidation, a few hours following training, is associated with altered contextual fear conditioning 24 h after irradiation and which brain region(s) might be involved in these effects. Brain immunoreactivity patterns of the immediately early gene c-Fos, a marker of cellular activity was used to determine which brain areas might be altered in post-training irradiation memory retention tasks. In this study, we show that post-training gamma irradiation exposure (1 Gy) enhanced contextual fear memory 24 h later and is associated with reduced cellular activation in the infralimbic cortex. Reduced GABA-ergic neurotransmission in parvalbumin-positive cells in the infralimbic cortex might play a role in this post-training radiation-enhanced contextual fear memory. [ABSTRACT FROM AUTHOR]

Rule switching is 1 among a diverse set of executive functions whose delicate interactions allows us to coordinate behavior appropriately to changing contexts and demands. Clinical assessments such as the Trail Making Test (TMT) estimate flexibility of rule switching, but such assessments can be challenging to interpret. TMT scores are sums of many choice response times (RTs): More time spent reflects not simply manual motor speed and visual scanning but also fluctuation of attention to sequence and less flexible switching among rules to reject many inappropriate targets and instead select the single next appropriate target. A growing consensus recognizes that the aggregate of many choice RTs reflect multiplicative interaction of factors across multiple scales, among which manual motor speed, counting up sequence, and rule-switching are just a few. Multiplicative interactions entail first, fractal temporal correlations and, more importantly, variability of fractality within the same series, that is, "multifractality," The authors analyzed circle-tracing data to test whether tracing variance, degree of fractal temporal correlations, and multifractality correlate with TMT scores. Despite the absence of effects of variance, stronger temporal correlations indicated poorer Trails B performance, but multifractality moderated this relationship. These results suggest potential markers for predicting rule-switching ability from motor behavior. (PsycINFO Database Record [ABSTRACT FROM AUTHOR]

Fractal scaling patterns, which entail a power-law relationship between magnitude of fluctuations in a variable and the scale at which the variable is measured, have been found in many aspects of human behavior. These findings have led to advances in behavioral models (e.g. providing empirical support for cascade-driven theories of cognition) and have had practical medical applications (e.g. providing new methods for early diagnosis of medical conditions). In the present paper, fractal analysis is used to investigate whether similar fractal scaling patterns exist in inter-click interval and peak–peak amplitude measurements of bottlenose dolphin click trains. Several echolocation recordings taken from two male bottlenose dolphins were analyzed using Detrended Fluctuation Analysis and Higuchi’s (1988) method for determination of fractal dimension. Both animals were found to exhibit fractal scaling patterns near what is consistent with persistent long range correlations. These findings suggest that recent advances in human cognition and medicine may have important parallel applications to echolocation as well. [ABSTRACT FROM AUTHOR]

The likelihood of suffering a concussion while playing a contact sport ranges from 15-45% per year of play. These rates are highly variable as athletes seldom report concussive symptoms, or do not recognize their symptoms. We performed a prospective cohort study (n = 206, aged 10-17) to examine visuomotor tracing to determine the sensitivity for detecting neuromotor components of concussion. Tracing variability measures were investigated for a mean shift with presentation of concussion-related symptoms and a linear return toward baseline over subsequent return visits. Furthermore, previous research relating brain injury to the dissociation of smooth movements into "submovements" led to the expectation that cumulative micropause duration, a measure of motion continuity, might detect likelihood of injury. Separate linear mixed effects regressions of tracing measures indicated that 4 of the 5 tracing measures captured both short-term effects of injury and longer-term effects of recovery with subsequent visits. Cumulative micropause duration has a positive relationship with likelihood of participants having had a concussion. The present results suggest that future research should evaluate how well the coefficients for the tracing parameter in the logistic regression help to detect concussion in novel cases. [ABSTRACT FROM AUTHOR]

Turing inspired a computer metaphor of the mind and brain that has been handy and has spawned decades of empirical investigation, but he did much more and offered behavioral and cognitive sciences another metaphor—that of the cascade. The time has come to confront Turing's cascading instability, which suggests a geometrical framework driven by power laws and can be studied using multifractal formalism and multiscale probability density function analysis. Here, we review a rapidly growing body of scientific investigations revealing signatures of cascade instability and their consequences for a perceiving, acting, and thinking organism. We review work related to executive functioning (planning to act), postural control (bodily poise for turning plans into action), and effortful perception (action to gather information in a single modality and action to blend multimodal information). We also review findings on neuronal avalanches in the brain, specifically about neural participation in body-wide cascades. Turing's cascade instability blends the mind, brain, and behavior across space and time scales and provides an alternative to the dominant computer metaphor. • Turing's computer metaphor of the mind and brain has inspired decades of research. • The time has come to confront Turing's another metaphor—that of cascading instability. • It is a power-law driven framework that can be studied using multifractal formalisms. • We review a rapidly growing body of scientific investigations on cascade instability. • Cascade instability blends the mind, brain, and behavior across space and time scales. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD. [ABSTRACT FROM AUTHOR]

Excess mortality and hospitalization have been identified after the 2-day gap in thrice-weekly hemodialysis patients compared with 1-day intervals, although findings vary internationally. Here we aimed to identify factors associated with mortality and hospitalization events in England using an incident cohort of 5864 hemodialysis patients from years 2002 to 2006 inclusive in the UK Renal Registry linked to hospitalization data. Higher admission rates were seen after the 2-day gap irrespective of whether thrice-weekly dialysis sequence commenced on a Monday or Tuesday (2.4 per year after the 2-day gap vs. 1.4 for the rest of the week, rate ratio 1.7). The greatest differences in admission rates were seen in patients admitted with fluid overload or with conditions associated with a high risk of fluid overload. Increased mortality following the 2-day gap was similarly independent of session pattern (20.5 vs. 16.7 per 100 patient years, rate ratio 1.22), with these increases being driven by out-of-hospital death (rate ratio 1.59 vs. 1.06 for in-hospital death). Non-white patients had an overall survival advantage, with the increased mortality after the 2-day gap being found only in whites. Thus, fluid overload may increase the risk of hospital admission after the 2-day gap and that the increased out-of-hospital mortality may relate to a higher incidence of sudden death. Future work should focus on exploring interventions in these subgroups. [ABSTRACT FROM AUTHOR]

The PTH family of ligands and receptors have a wide range of vital functions from calcium homeostasis to tissue and bone development from the embryo to adult. This family has undergone whole genome duplication events predating vertebrate evolution, indicating more primitive and ancient functions other than skeletal development. The N-terminal region of the ligands, have been widely studied by biophysical and functional analysis, resulting in the discovery of key characteristics essential for ligand-receptor activation being elucidated. Multi-substituted amino acid analogs with differential binding affinities and either antagonistic or agonistic signalling potencies have been created based on these findings allowing for improvement on potential therapies affected by the PTH system in skeletal and embryonic development. The PTH family has diversely evolved to cover a wide range of pivotal pathways crucial to growth and development throughout all animal life. [ABSTRACT FROM AUTHOR]

It remains challenging to accurately predict whether an individual arteriovenous fistula (AVF) will mature and be useable for haemodialysis vascular access. Current best practice involves the use of routine clinical assessment and ultrasonography complemented by selective venography and magnetic resonance imaging. The purpose of this literature review is to describe current practices in relation to pre-operative assessment prior to AVF formation and highlight potential areas for future research to improve the clinical prediction of AVF outcomes. [ABSTRACT FROM AUTHOR]

Nesting is a major cornerstone in ecological theorizing about visual perception, through both nesting of surface layout in locomotory movements and nesting of visually available surfaces within each other, from focal to peripheral vision. This work sought to probe these nesting relationships by examining the effects of the visual periphery on the strength of interactions among nested time scales in head sway. That is, we tested whether spatial nesting of the focal within peripheral visual fields stimulated nonlinear interactions amid temporal nesting. We examined head sway during 2 variants of the Fitts task, one involving manual pointing by seated participants and another involving walking comfortably with upright standing posture. All participants completed both tasks but were randomly assigned to experience these tasks with or without the visual periphery available. Multifractal analysis of head sway revealed that visual availability of the periphery promoted nonlinear interactions across nested time scales, but this effect depended on how much head sway extended across a plane than more ballistically along a single axis of variability. [ABSTRACT FROM PUBLISHER]

Intermodal integration required for perceptual learning tasks is rife with individual differences. Participants vary in how they use perceptual information to one modality. One participant alone might change her own response over time. Participants vary further in their use of feedback through one modality to inform another modality. Two experiments test the general hypothesis that perceptual-motor fluctuations reveal both information use within modality and coordination among modalities. Experiment I focuses on perceptual learning in dynamic touch, in which participants use exploratory hand-wielding of unseen objects to make visually guided length judgments and use visual feedback to rescale their judgments of the same mechanical information. Previous research found that the degree of fractal temporal scaling (i.e., "fractality") in hand-wielding moderates the use of mechanical information. Experiment 1 shows that head-sway fractality moderates the use of visual information. Further, experience with feedback increases head-sway fractality and prolongs its effect on later hand-wielding fractality. Experiment 2 replicates effects of head-sway fractality moderating use of visual information in a purely visual-judgment task. Together, these findings suggest that fractal fluctuations may provide a modal-general window onto not just how participants use perceptual information but also how well they may integrate information among different modalities. [ABSTRACT FROM AUTHOR]

Traditional theories of psychology define the cognitive system as composed of insular, encapsulated components, controlled by a central executive. An alternative hypothesis suggests that cognitive control arises from the complex interaction among temporal scales of activity within the system. We examined the hand motions of preschool-age participants gathered during an executive-function task, card sorting, for evidence of multiplicative interactions across temporal scales. The time series of hand motions were submitted to iterated amplitude adjusted Fourier transformation (IAAFT), a surrogate data analysis technique that removes nonlinear, multiscale dependencies while preserving the linear structure of the time series. We found that removing multiscale effects via IAAFT led to a significant change in the width of the multifractal spectrum, an indicator of multiplicative interactions. The results suggest that cognitive control may arise from the interactions among temporal scales of activity within the system rather than as the result of a central executive. [ABSTRACT FROM AUTHOR]

Pole balancing is a key task for probing the prospective control that organisms must engage in for purposeful action. The temporal structure of pole-balancing behaviors will reflect the on-line operation of control mechanisms needed to maintain an upright posture. In this study, signatures of multifractality are sought and found in time series of the vertical angle of a pole balanced on the fingertip. Comparisons to surrogate time series reveal multiplicative-cascade dynamics and interactivity across scales. In addition, simulations of a pole-balancing model generating on-off intermittency [J. L. Cabrera and J. G. Milton, Phys. Rev. Lett. 89, 158702 (2002)] were analyzed. Evidence of multifractality is also evident in simulations, though comparing simulated and participant series reveals a significantly greater contribution of cross-scale interactivity for the latter. These findings suggest that multiplicative-cascade dynamics are an extension of on-off intermittency and play a role in prospective coordination. [ABSTRACT FROM AUTHOR]

Dysregulation of hypothalamic-pituitary-adrenal ( HPA) axis activation is associated with changes in addiction-related behaviors. In this study, we tested whether sex differences in the acute effects of methamphetamine ( MA) exposure involve differential activation of the HPA axis. Male and female mice were injected with MA (1 mg/kg) or saline for comparison of plasma corticosterone and analysis of the immediate early gene c-Fos in brain. There was a prolonged elevation in corticosterone levels in female compared to male mice. C-Fos was elevated in both sexes following MA in HPA axis-associated regions, including the hypothalamic paraventricular nucleus ( PVN), central amygdala, cingulate, and CA3 hippocampal region. MA increased the number of c-Fos and c-Fos/glucocorticoid receptor ( GR) dual-labeled cells to a greater extent in males than females in the cingulate and CA3 regions. MA also increased the number of c-fos/vasopressin dual-labeled cells in the PVN as well as the number and percentage of c-Fos/ GR dual-labeled cells in the PVN and central amygdala, although no sex differences in dual labeling were found in these regions. Thus, sex differences in MA-induced plasma corticosterone levels and activation of distinct brain regions and proteins involved in HPA axis regulation may contribute to sex differences in acute effects of MA on the brain. [ABSTRACT FROM AUTHOR]

ABSTRACT Estrogen receptors regulate multiple brain functions, including stress, sexual, and memory-associated behaviors as well as controlling neuroendocrine and autonomic function. During development, estrogen signaling is involved in programming adult sex differences in physiology and behavior. Expression of estrogen receptor α changes across development in a region-specific fashion. By contrast, estrogen receptor β (ERβ) is expressed in many brain regions, yet few studies have explored sex and developmental differences in its expression, largely because of the absence of selective reagents for anatomical localization of the protein. This study utilized bacterial artificial chromosome transgenic mice expressing ERβ identified by enhanced green fluorescent protein (EGFP) to compare expression levels and distribution of ERβ in the male and female mouse forebrain on the day of birth (P0), on postnatal day 4 (P4), and on P21. By using qualitative analysis, we mapped the distribution of ERβ-EGFP and found developmental alterations in ERβ expression within the cortex, hippocampus, and hypothalamic regions including the arcuate, ventromedial, and paraventricular nuclei. We also report a sex difference in ERβ in the bed nucleus of the stria terminalis, with males showing greater expression at P4 and P21. Another sex difference was found in the anteroventral periventricular nucleus of P21, but not P0 or P4, mice, in which ERβ-EGFP-immunoreactive cells were densely clustered near the third ventricle in females but not males. These developmental changes and sex differences in ERβ indicate a mechanism through which estrogens might differentially affect brain functions or program adult physiology at select times during development. J. Comp. Neurol. 522:358-371, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Highlights: [•] Identification of genes that encode for β-catenin, Sfrp and SOST/SOSTDC1 in cartilaginous fish. [•] The elephant shark β-catenin, Sfrp and SOST/SOSTDC1 genes are expressed in cartilage. [•] Elephant shark β-catenin protein is localized in skeletal tissues. [ABSTRACT FROM AUTHOR]

Background Stroke is a leading cause of death in Asia; however, many estimates of stroke mortality are based on epidemiological models rather than empirical data. Since 2005, initiatives have been undertaken in a number of Asian countries to strengthen and analyse vital registration data. This has increased the availability of empirical data on stroke mortality. Aims The aim of this paper is to present estimates of stroke mortality for Indonesia, Myanmar, Viet Nam, Thailand, and Malaysia, which have been derived using these empirical data. Methods Age-specific stroke mortality rates were calculated in each of the five countries, and adjusted for data completeness or misclassification where feasible. All data were age-standardized and the resulting rates were compared with World Health Organization estimates, which are largely based on epidemiological models. Results Using empirical data, stroke ranked as the leading cause of death in all countries except Malaysia, where it ranked as the second leading cause. Age-standardized rates for males ranged from 94 per 100 000 in Thailand, to over 300 per 100 000 in Indonesia. In all countries, rates were higher for males than for females, and those compiled from empirical data were generally higher than modelled estimates published by World Health Organization. Conclusions This study highlights the extent of stroke mortality in selected Asian countries, and provides important baseline information to investigate the aetiology of stroke in Asia and design appropriate public health strategies to address the rapidly growing burden from stroke. [ABSTRACT FROM AUTHOR]

Aims Excessively acidic urine is the dominant factor in uric acid stone formation. Recent evidence implicating insulin resistance has revived interest in its causation. We reviewed data on uric acid stone formers attending a general stones clinic to find out whether this supports and adds to current concepts. Methods A retrospective database study of 1504 stone formers investigated at the Southampton renal stones clinic from 1990 to March 2007. Uric acid stone formers and idiopathic calcium stone formers were compared using non-parametric tests. Results Fifty-nine patients (3.9%; 43 men) had uric acid stones. In men the commonest associated conditions were diabetes (20%), gout (20%) and an ileostomy (15%); in women, diabetes (33%), urinary infections (27%) and hyperparathyroidism (20%). Most patients with diabetes (85% of men, 75% of women), however, produced calcium stones. Risk factors did not differ significantly between calcium and uric acid stone formers with diabetes, gout or ileostomies. The median urine pH of men with idiopathic calcium stones was 6.20, idiopathic uric acid stones 5.47, diabetes 5.68, gout 6.05, diabetes and gout 5.20 and ileostomy 5.10. Plasma urate was higher with gout and idiopathic uric acid stones. Urate excretion was increased in gout. Oxalate excretion was lower with idiopathic uric acid stones (new finding). Urine volume decreased and oxalate concentration increased with ileostomy. Conclusions Uric acid stones are increased in diabetes, but most patients with diabetes make calcium stones. Different mechanisms may explain low pH with diabetes, gout and idiopathic stones. Low oxalate excretion with idiopathic urate stones needs confirmation. [ABSTRACT FROM AUTHOR]

Abstract: The present work documents reanalysis of previous research by Priplata and colleagues (Priplata et al., 2002) into the effects of subthreshold vibratory stimulation to the plantar surface of the foot on postural stability during quiet standing. In stochastic resonance, stimulating a nonlinear system with noise can promote system stability. Stochastic resonance has been proposed to have clinical applications as an intervention that might help to stabilize posture. Insoles designed to stimulate the plantar surface of the foot with uncorrelated white-noise fluctuations have been shown to reduce a number of standard measures of postural variability. An important remaining concern is that the efficacy of stochastic-resonance applications is subject to strong individual differences. Our reanalysis of data from Priplata et al.’s original study provides evidence that effects of uncorrelated fluctuations in subthreshold vibratory stimulation are moderated by temporally correlated fluctuations in postural sway. We suggest how future development might capitalize on this finding to fine-tune existing stochastic-resonance applications to posture. [Copyright &y& Elsevier]

Abstract: The potential energy of the infinite periodic chain model of polyacetylene (pPA) is symmetric with two equivalent minima separated by the Peierls’ stabilization barrier. In this work it is shown how an energy scale and vibrational energy levels for this highly anharmonic Peierls’ degree of freedom can be estimated. Particular attention is given to the potential energy increase for large deformations. Two empirical methods and direct periodic boundary condition (PBC) density functional theory (DFT) calculations are in semi-quantitative agreement with each other. Each lead to the conclusion that pPA has a zero-point level that is above the Peierls’ barrier. The argument does not depend critically on the barrier height or the other parameters of the model or the computation method. It is concluded that pPA will not exhibit bond alternation since two stable structures are not possible due primarily to the stiffness of the underlying Cond system. [Copyright &y& Elsevier]

Abstract: Our previous work interpreted single-lognormal fits to inter-gaze distance (i.e., “gaze steps”) histograms as evidence of multiplicativity and hence interactions across scales in visual cognition. Bogartz and Staub (2012) proposed that gaze steps are additively decomposable into fixations and saccades, matching the histograms better and illustrating how additive processes can generate tailed histograms. In this reply, we consider the validity of fixation-versus-saccade distinctions, reviewing eye-movement literature and re-analyzing our original data. Careful examination of empirical literature undermines rigid fixation-versus-saccade distinctions. By comparing original gaze-step series with surrogate data, we present new evidence that temporal clustering in gaze-step data reflects interactive rather than additive processes. We conclude by discussing the relation between traditional notions of interactivity between components and complex-systems notions of interactivity across scales. [Copyright &y& Elsevier]