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Purpose: In resistance training (RT), the change in volume-load from training sessions (TS) to TS is an indicator of training progress. Resulting growth trajectories are likely to differ between individuals. Understanding this variation is important for exercise planning in general, but even more for clinical populations. We investigated this variation in breast cancer patients undergoing treatment. Methods: Data of 69 patients from two randomized controlled trails were investigated. They conducted a 12-week RT program. We fitted a quadratic Bayesian regression model to the baseline standardized volume-load over the course of the intervention. We allowed all parameters to vary both between exercises and between individuals. Results: We observed a positive linear component of 0.093 (95% uncertainty interval (UI) 0.058 to 0.120) and a negative quadratic component of − 0.002 (95% UI -0.008 to 0.001) for the mean trajectory of the change in volume-load. For the different exercises, we observed a dispersion for both the linear (0.043, 95% UI 0.018 to 0.082) and the quadratic component (0.002, 95% UI < 0.001 to 0.004). Variation between individual appears to be approximately four times larger. We also observed between-exercise variation within individuals. Extrapolation of the regression model indicates training progression stagnates after 20.6 TS (95% UI 14.8 to 44.4). Conclusion: There is substantial variation in RT response between breast cancer patients undergoing tumor therapy and in-between exercises. The non-linear trajectory indicates that training progression will eventually plateau, demanding periodization and timely modification. Trial registration: BEATE Study: NCT01106820, Date: April 20, 2010; BEST Study: NCT01468766, Date: November 9, 2011. [ABSTRACT FROM AUTHOR]

Over the last two decades, the analogue report task has become a standard method for measuring the fidelity of visual representations across research domains including perception, attention, and memory. Despite its widespread use, there has been no methodical investigation of the different task parameters that might contribute to response variability. To address this gap, we conducted two experiments manipulating components of a typical analogue report test of memory for colour hue. We found that human response errors were independently affected by changes in storage and maintenance requirements of the task, demonstrated by a strong effect of set size even in the absence of a memory delay. In contrast, response variability remained unaffected by physical size of the colour wheel, implying negligible contribution of motor noise to task performance, or by its chroma radius, highlighting non-uniformity of the standard colour space. Comparing analogue report to a matched forced-choice task, we found variation in adjustment criterion made a limited contribution to analogue report variability, becoming meaningful only with low representational noise. Our findings validate the analogue report task as a robust measure of representational fidelity for most purposes, while also quantifying non-representational sources of noise that would limit its reliability in specialized settings. [ABSTRACT FROM AUTHOR]

Although the Bayesian paradigm is an important benchmark in studies of human inference, the extent to which it provides a useful framework to account for human behavior remains debated. We document systematic departures from Bayesian inference under correct beliefs, even on average, in the estimates by experimental subjects of the probability of a binary event following observations of successive realizations of the event. In particular, we find underreaction of subjects' estimates to the evidence ("conservatism") after only a few observations and at the same time overreaction after longer sequences of observations. This is not explained by an incorrect prior nor by many common models of Bayesian inference. We uncover the autocorrelation in estimates, which suggests that subjects carry imprecise representations of the decision situations, with noise in beliefs propagating over successive trials. But even taking into account these internal imprecisions and assuming various incorrect beliefs, we find that subjects' updates are inconsistent with the rules of Bayesian inference. We show how subjects instead considerably economize on the attention that they pay to the information relevant to the decision, and on the degree of control that they exert over their precise response, while giving responses fairly adapted to the task. A "noisy-counting" model of probability estimation reproduces the several patterns we exhibit in subjects' behavior. In sum, human subjects in our task perform reasonably well while greatly minimizing the amount of information that they pay attention to. Our results emphasize that investigating this economy of attention is crucial in understanding human decisions. [ABSTRACT FROM AUTHOR]

Abstract Background Clopidogrel has been the primary choice of antiplatelet in ischemic stroke that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. P-glycoprotein (P-gp) multidrug resistance-1 (MDR1) is a transmembrane efflux transporter in intestinal cells that plays a significant role in clopidogrel absorption, therefore may affect platelet aggregation. P-gp is encoded by the ABCB1 gene. This study aims to evaluate the effect of ABCB1 polymorphism on clopidogrel response variability in ischemic stroke patients and its genotype frequency. Methods A cross-sectional study was conducted in ischemic stroke patients who received clopidogrel between 2020 and 2023 in RSUI/RSCM. All subjects were assessed for ABCB1 polymorphisms C3435T and C1236T. Platelet aggregation were measured using VerifyNow PRU. Clopidogrel response variability was classified into unresponsive (> 208 PRU), responsive (95–208 PRU), and bleeding risk (

Background: Clopidogrel has been the primary choice of antiplatelet in ischemic stroke that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. P-glycoprotein (P-gp) multidrug resistance-1 (MDR1) is a transmembrane efflux transporter in intestinal cells that plays a significant role in clopidogrel absorption, therefore may affect platelet aggregation. P-gp is encoded by the ABCB1 gene. This study aims to evaluate the effect of ABCB1 polymorphism on clopidogrel response variability in ischemic stroke patients and its genotype frequency. Methods: A cross-sectional study was conducted in ischemic stroke patients who received clopidogrel between 2020 and 2023 in RSUI/RSCM. All subjects were assessed for ABCB1 polymorphisms C3435T and C1236T. Platelet aggregation were measured using VerifyNow PRU. Clopidogrel response variability was classified into unresponsive (> 208 PRU), responsive (95–208 PRU), and bleeding risk (< 95 PRU). Results: 124 subjects enrolled in this study, with 12,9% of subjects classified as non-responsive/resistant, 49,5% as responsive, and 41,9% as bleeding risk. ABCB1 C1236T homozygote wildtype (CC) was associated with 3,76 times higher bleeding risk than other variants (p = 0,008; 95%CI 1,41 − 10,07). Genotype frequency of ABCB1 C3435T homozygote wildtype, heterozygote, and homozygote variants were 35,9%, 43,5% and 16,9%, respectively; while the genotype frequency of ABCB1 C1236T were 17,8%, 39,5%, and 42,7%, respectively. Conclusion: ABCB1 C1236T homozygote wildtype was associated with 3,76 times higher bleeding risk than other variants. The most common genotype frequency of ABCB1 C1236T was homozygote variant; while for ABCB1 C3435T was heterozygote. [ABSTRACT FROM AUTHOR]

Adult visual plasticity underlying local remodeling of the cortical circuitry in vivo appears to be associated with a spatiotemporal pattern of strongly increased spontaneous and evoked activity of populations of cells. Here we review and discuss pioneering work by us and others about principles of plasticity in the adult visual cortex, starting with our study which showed that a confined lesion in the cat retina causes increased excitability in the affected region in the primary visual cortex accompanied by fine-tuned restructuring of neuronal function. The underlying remodeling processes was further visualized with voltage-sensitive dye (VSD) imaging that allowed a direct tracking of retinal lesion-induced reorganization across horizontal cortical circuitries. Nowadays, application of noninvasive stimulation methods pursues the idea further of increased cortical excitability along with decreased inhibition as key factors for the induction of adult cortical plasticity. We used high-frequency transcranial magnetic stimulation (TMS), for the first time in combination with VSD optical imaging, and provided evidence that TMS-amplified excitability across large pools of neurons forms the basis for noninvasively targeting reorganization of orientation maps in the visual cortex. Our review has been compiled on the basis of these four own studies, which we discuss in the context of historical developments in the field of visual cortical plasticity and the current state of the literature. Overall, we suggest markers of LTP-like cortical changes at mesoscopic population level as a main driving force for the induction of visual plasticity in the adult. Elevations in excitability that predispose towards cortical plasticity are most likely a common property of all cortical modalities. Thus, interventions that increase cortical excitability are a promising starting point to drive perceptual and potentially motor learning in therapeutic applications. [ABSTRACT FROM AUTHOR]

Mechanosensory cells in the leech share several common features with mechanoreceptors in the human glabrous skin. Previous studies showed that the six T (touch) cells in each body segment of the leech are highly variable in their responses to somatic current injection and change their excitability over time. Here, we investigate three potential reasons for this variability in excitability by comparing the responses of T cells at two soma locations (T2 and T3): (1) Differential effects of time-dependent changes in excitability, (2) divergent synaptic input from the network, and (3) different anatomical structures. These hypotheses were explored with a combination of electrophysiological double recordings, 3D reconstruction of neurobiotin-filled cells, and compartmental model simulations. Current injection triggered significantly more spikes with shorter latency and larger amplitudes in cells at soma location T2 than at T3. During longer recordings, cells at both locations increased their excitability over time in the same way. T2 and T3 cells received the same amount of synaptic input from the unstimulated network, and the polysynaptic connections between both T cells were mutually symmetric. However, we found a striking anatomical difference: While in our data set all T2 cells innervated two roots connecting the ganglion with the skin, 50% of the T3 cells had only one root process. The sub-sample of T3 cells with one root process was significantly less excitable than the T3 cells with two root processes and the T2 cells. To test if the additional root process causes higher excitability, we simulated the responses of 3D reconstructed cells of both anatomies with detailed multi-compartment models. The anatomical subtypes do not differ in excitability when identical biophysical parameters and a homogeneous channel distribution are assumed. Hence, all three hypotheses may contribute to the highly variable T cell responses, but none of them is the only factor accounting for the observed systematic difference in excitability between cells at T2 vs. T3 soma location. Therefore, future patch clamp and modeling studies are needed to analyze how biophysical properties and spatial distribution of ion channels on the cell surface contribute to the variability and systematic differences of electrophysiological phenotypes. [ABSTRACT FROM AUTHOR]

Metformin constitutes the foundation therapy in type 2 diabetes (T2D). Despite its multiple beneficial effects and widespread use, there is considerable inter-individual variability in response to metformin. Our objective is to identify metabolic signatures associated with poor and good responses to metformin, which may improve our ability to predict outcomes for metformin treatment. In this cross-sectional study, clinical and metabolic data for 119 patients with type 2 diabetes taking metformin were collected from the Qatar Biobank. Patients were empirically dichotomized according to their HbA1C levels into good and poor responders. Differences in the level of metabolites between these two groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. Good responders showed increased levels of sphingomyelins, acylcholines, and glutathione metabolites. On the other hand, poor responders showed increased levels of metabolites resulting from glucose metabolism and gut microbiota metabolites. The results of this study have the potential to increase our knowledge of patient response variability to metformin and carry significant implications for enabling personalized medicine. [ABSTRACT FROM AUTHOR]

Sodium–glucose cotransporter-2 (SGLT2) inhibitors improve markers for renal and cardiovascular outcomes in patients with and without type 2 diabetes (T2D). To assess whether individual differences in plasma drug exposure can explain inter-individual response variation, we characterized the exposure–response relationship for two SGLT2 inhibitors on several clinical and kidney hemodynamic variables. Data were obtained from two studies, RED and RECOLAR, assessing the effects of once-daily 10 mg dapagliflozin or empagliflozin, respectively, on kidney hemodynamics in patients with T2D. Individual plasma exposure was estimated using non-compartmental analyses and exposure–response relationships were assessed using linear mixed-effects models. In 23 patients participating in RED, the dapagliflozin geometric mean apparent area under the concentration-time curve during one dosing interval at steady state (AUC0–tau,ss) was 1153.1 µg/L*h (coefficient of variation (CV) 81.8%) and associated, per doubling, with decreases in body weight (0.29 kg, p < 0.001), systolic blood pressure (0.80 mmHg, p = 0.002), measured glomerular filtration rate (mGFR) (0.83 mL/min, p = 0.03), and filtration fraction (0.09%, p = 0.04). In 20 patients participating in RECOLOR, the empagliflozin geometric mean AUC0–tau,ss was 2035.7 nmol/L*h (CV 48.4%) and associated, per doubling, with decreases in body weight (0.13 kg, p = 0.002), systolic blood pressure (0.65 mmHg, p = 0.045), and mGFR (0.78 mL/min, p = 0.002). To conclude, dapagliflozin and empagliflozin plasma exposure was highly variable between patients and associated with inter-individual variation in response variables. [ABSTRACT FROM AUTHOR]

Widely used in neuroscience the averaging of event related potentials is based on the assumption that small responses to the investigated events are present in every trial but can be hidden under the random noise. This situation often takes place, especially in experiments performed at hierarchically lower levels of sensory systems. However, in the studies of higher order complex neuronal networks evoked responses might appear only under particular conditions and be absent otherwise. We encountered this problem studying a propagation of interoceptive information to the cortical areas in the sleep-wake cycle. Cortical responses to various visceral events were present during some periods of sleep, then disappeared for a while and restored again after a period of absence. Further investigation of the viscero-cortical communication required a method that would allow labeling the trials contributing to the averaged event related responses--"efficient trials," and separating them from the trials without any response. Here we describe a heuristic approach to solving this problem in the context of viscero-cortical interactions occurring during sleep. However, we think that the proposed technique can be applicable to any situation where neuronal processing of the same events is expected to be variable due to internal or external factors modulating neuronal activity. The method was first implemented as a script for Spike 2 program version 6.16 (CED). However, at present a functionally equivalent version of this algorithm is also available as Matlab code at https://github.com/george-fedorov/erp-correlations. [ABSTRACT FROM AUTHOR]

Mechanosensory cells in the leech share several common features with mechanoreceptors in the human glabrous skin. Previous studies showed that the six T (touch) cells in each body segment of the leech are highly variable in their responses to somatic current injection and change their excitability over time. Here, we investigate three potential reasons for this variability in excitability by comparing the responses of T cells at two soma locations (T2 and T3): (1) Differential effects of time-dependent changes in excitability, (2) divergent synaptic input from the network, and (3) different anatomical structures. These hypotheses were explored with a combination of electrophysiological double recordings, 3D reconstruction of neurobiotin-filled cells, and compartmental model simulations. Current injection triggered significantly more spikes with shorter latency and larger amplitudes in cells at soma location T2 than at T3. During longer recordings, cells at both locations increased their excitability over time in the same way. T2 and T3 cells received the same amount of synaptic input from the unstimulated network, and the polysynaptic connections between both T cells were mutually symmetric. However, we found a striking anatomical difference: While in our data set all T2 cells innervated two roots connecting the ganglion with the skin, 50% of the T3 cells had only one root process. The sub-sample of T3 cells with one root process was significantly less excitable than the T3 cells with two root processes and the T2 cells. To test if the additional root process causes higher excitability, we simulated the responses of 3D reconstructed cells of both anatomies with detailed multi-compartment models. The anatomical subtypes do not differ in excitability when identical biophysical parameters and a homogeneous channel distribution are assumed. Hence, all three hypotheses may contribute to the highly variable T cell responses, but none of them is the only factor accounting for the observed systematic difference in excitability between cells at T2 vs. T3 soma location. Therefore, future patch clamp and modeling studies are needed to analyze how biophysical properties and spatial distribution of ion channels on the cell surface contribute to the variability and systematic differences of electrophysiological phenotypes.

Widely used in neuroscience the averaging of event related potentials is based on the assumption that small responses to the investigated events are present in every trial but can be hidden under the random noise. This situation often takes place, especially in experiments performed at hierarchically lower levels of sensory systems. However, in the studies of higher order complex neuronal networks evoked responses might appear only under particular conditions and be absent otherwise. We encountered this problem studying a propagation of interoceptive information to the cortical areas in the sleep-wake cycle. Cortical responses to various visceral events were present during some periods of sleep, then disappeared for a while and restored again after a period of absence. Further investigation of the viscero-cortical communication required a method that would allow labeling the trials contributing to the averaged event related responses–“efficient trials,” and separating them from the trials without any response. Here we describe a heuristic approach to solving this problem in the context of viscero-cortical interactions occurring during sleep. However, we think that the proposed technique can be applicable to any situation where neuronal processing of the same events is expected to be variable due to internal or external factors modulating neuronal activity. The method was first implemented as a script for Spike 2 program version 6.16 (CED). However, at present a functionally equivalent version of this algorithm is also available as Matlab code at https://github.com/george-fedorov/erp-correlations.

Metformin constitutes the foundation therapy in type 2 diabetes (T2D). Despite its multiple beneficial effects and widespread use, there is considerable inter-individual variability in response to metformin. Our objective is to identify metabolic signatures associated with poor and good responses to metformin, which may improve our ability to predict outcomes for metformin treatment. In this cross-sectional study, clinical and metabolic data for 119 patients with type 2 diabetes taking metformin were collected from the Qatar Biobank. Patients were empirically dichotomized according to their HbA1C levels into good and poor responders. Differences in the level of metabolites between these two groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. Good responders showed increased levels of sphingomyelins, acylcholines, and glutathione metabolites. On the other hand, poor responders showed increased levels of metabolites resulting from glucose metabolism and gut microbiota metabolites. The results of this study have the potential to increase our knowledge of patient response variability to metformin and carry significant implications for enabling personalized medicine.

The accurate quantification of the random spatial variation of material properties at different scales is crucial for the systematic propagation of uncertainties through engineering models. In a previous work, the spatial variability of the apparent material properties of two-phase composites has been quantified in a Bayesian framework. This framework enables a consistent modeling of the statistical uncertainty in the parameters of the respective mesoscale random fields and also allows selecting the most plausible correlation model among different models belonging to the Matérn family. In this work, the most plausible random field model is employed in the context of uncertainty propagation of composite structures. Sample functions of the mesoscale random fields are generated using a covariance decomposition approach and the response variability of various composite structures is computed through Monte Carlo simulation. Parametric investigations are conducted to highlight the effect of the identified parameter uncertainty on structural response variability.

Given the limited attention on a combined exercise and education approach for those with chronic musculoskeletal pain disorder such as fibromyalgia, the purpose of this was to evaluate the efficacy of a combined exercise and education programme on symptoms and physical fitness in participants with fibromyalgia. Using a prospective observational cohort study, participants with fibromyalgia (n = 75) volunteered. The 6-minute-walk-test (6MWT) and revised-fibromyalgia-impact-questionnaire (FIQR) were used before, after (6 weeks) and 6-months post an exercise and education programme. Forty-three participants (age = 49.7 ± 15.2 y) completed the 6-week programme, with improvements observed for the 6MWT (67 m, p < 0.001) and FIQR (11 AU, p < 0.001), though only two (6MWT) and five (FIQR) participants, respectively, achieved the minimal clinically important difference (MCID). Using 74% of the intial sample, a small-to-moderate improvement in scores were observed across the 6-month period for the 6MWT (37 m, p = 0.002) and FIQR (3 AU, p = 0.01), with only two participants achieving the MCID for the 6MWT. The results in this study indiciate small-to-moderate improvements in the 6MWT and FIQR after a combined exercise and education programme, with direct delivery being more effective. A six-week exercise and education programme elicited moderate, short-term (6 weeks) benefits on physical fitness and key symptoms in patients with fibromyalgia. On average, these benefits were sustained in the long-term (6 months) following the programme but were small-to-moderate and lower than the MCID. Regular follow-up may be required to improve adherence to the education and exercise programme and maintain or increase the observed improvements in 6MWT and FIQR. [ABSTRACT FROM AUTHOR]

During an earthquake, steel frame buildings with bracings are prone to high absolute floor acceleration demands, thereby causing damage to acceleration‐sensitive non‐structural elements and building content. Inelastic deformations in steel bracings and/or their end connections often necessitate the use of capacity design rules to meet the life safety requirements established by seismic design standards. This paper presents an alternative steel frame building configuration where energy dissipation is mostly achieved through friction dampers acting as dissipative connectors between the floor diaphragms and the steel frame(s) with bracings. The dampers consist of friction pads made from composite materials which are not susceptible to galvanic corrosion. Physical experiments suggest that the friction pads are effective in dissipating the seismic energy through friction. Nonlinear response history analyses of a prototype 6‐storey steel frame building featuring friction dampers as dissipative floor connectors demonstrate that a) higher mode effects are mitigated; b) capacity‐design in the steel frame(s) with bracings is not imperative to ensure a uniform lateral drift distribution; and c) the seismic response variability in storey‐based engineering demand parameters is reduced remarkably compared with that of the conventional counterpart with rigid diaphragms. All‐in‐all, the alternative building configuration has high potential to minimize earthquake‐induced repairs over a building's service life. [ABSTRACT FROM AUTHOR]

Friction dampers are one of the most common secondary structures utilized to alleviate excessive vibration amplitudes in turbomachinery applications. In this paper, the dynamic behavior of the turbine bladed disks coupled with one of the special damper designs, the so-called Midspan Dampers (MSDs) that is commonly used in steam turbines of Baker Hughes Company, is thoroughly studied. Friction between the blade and the damper is modeled through a large number of contact nodes by using two-dimensional contact elements with a variable normal load. In the solution procedure, the coupled static/dynamic Harmonic Balance approach is utilized for the first time in the assessment of the dissipation capability of MSDs, computationally shown by predicting the forced response levels of the system at different resonances. Moreover, it is demonstrated that the nonlinear dynamic response is non-unique and it may vary considerably even if all the user-controlled inputs are kept identical. This phenomenon is a novel observation for MSDs, and it is explained by an uncertainty present in the contact forces. Contact conditions corresponding to multiple responses are also investigated to unveil the different kinematics of the damper under the same nominal conditions. [ABSTRACT FROM AUTHOR]

Over the past two decades, the postulated modulatory effects of transcranial direct current stimulation (tDCS) on the human brain have been extensively investigated. However, recent concerns on reliability of tDCS effects have been raised, principally due to reduced replicability and to interindividual variability in response to tDCS. These inconsistencies are likely due to the interplay between the level of induced cortical excitability and unaccounted structural and state‐dependent functional factors. On these grounds, we aimed at verifying whether the behavioural effects induced by a common tDCS montage (F3‐rSOA) were influenced by the participants' arousal levels, as part of a broader mechanism of state‐dependency. Pupillary dynamics were recorded during an auditory oddball task while applying either a sham or real tDCS. The tDCS effects were evaluated as a function of subjective and physiological arousal predictors (STAI‐Y State scores and pre‐stimulus pupil size, respectively). We showed that prefrontal tDCS hindered task learning effects on response speed such that performance improvement occurred during sham, but not real stimulation. Moreover, both subjective and physiological arousal predictors significantly explained performance during real tDCS, with interaction effects showing performance improvement only with moderate arousal levels; likewise, pupil response was affected by real tDCS according to the ongoing levels of arousal, with reduced dilation during higher arousal trials. These findings highlight the potential role of arousal in shaping the neuromodulatory outcome, thus emphasizing a more careful interpretation of null or negative results while also encouraging more individually tailored tDCS applications based on arousal levels, especially in clinical populations. [ABSTRACT FROM AUTHOR]

Contrast perception is a fundamental visual ability that allows us to distinguish objects from the background. However, whether it is perturbed by chronic exposure to environmental xenoestrogen, bisphenol A (BPA), is still elusive. Here, we used adult cats to explore BPA-induced changes in contrast sensitivity (CS) and its underlying neuronal coding mechanism. Behavioral results showed that 14 days of BPA exposure (0.4 mg/kg/day) was sufficient to induce CS declines at the tested spatial frequencies (0.05–2 cycles/deg) in all four cats. Furthermore, based on multi-channel electrophysiological recording and interneuronal correlation analysis, we found that the BPA-exposed cats exhibited an obvious up-regulation in noise correlation in the primary visual cortex (area 17, A17), thus providing a population neuronal coding basis for their perceptual dysfunction. Moreover, single neuron responses in A17 of BPA-exposed cats revealed a slight but marked decrease in CS compared to that of control cats. Additionally, these neuronal responses presented an overt decrease in signal-to-noise ratio, accompanied by increased trial-to-trial response variability (i.e., noise). To some extent, these neuron population and unit dysfunctions in A17 of BPA-exposed cats were attributable to decreased response activity of fast-spiking neurons. Together, our findings demonstrate that chronic BPA exposure restricts contrast perception, in response to impoverished neuronal coding ability in A17. [ABSTRACT FROM AUTHOR]

To make informed decisions in natural environments that change over time, humans must update their beliefs as new observations are gathered. Studies exploring human inference as a dynamical process that unfolds in time have focused on situations in which the statistics of observations are history-independent. Yet, temporal structure is everywhere in nature and yields history-dependent observations. Do humans modify their inference processes depending on the latent temporal statistics of their observations? We investigate this question experimentally and theoretically using a change-point inference task. We show that humans adapt their inference process to fine aspects of the temporal structure in the statistics of stimuli. As such, humans behave qualitatively in a Bayesian fashion but, quantitatively, deviate away from optimality. Perhaps more importantly, humans behave suboptimally in that their responses are not deterministic, but variable. We show that this variability itself is modulated by the temporal statistics of stimuli. To elucidate the cognitive algorithm that yields this behavior, we investigate a broad array of existing and new models that characterize different sources of suboptimal deviations away from Bayesian inference. While models with "output noise" that corrupts the response-selection process are natural candidates, human behavior is best described by sampling-based inference models, in which the main ingredient is a compressed approximation of the posterior, represented through a modest set of random samples and updated over time. This result comes to complement a growing literature on sample-based representation and learning in humans. [ABSTRACT FROM AUTHOR]

New Findings: What is the topic of this review?Biological and methodological factors associated with the variable changes in cardiorespiratory fitness in response to endurance training.What advances does it highlight?Several biological and methodological factors exist that each contribute, to a given extent, to response variability. Notably, prescribing exercise intensity relative to physiological thresholds reportedly increases cardiorespiratory fitness response rates compared to when prescribed relative to maximum physiological values. As threshold‐based approaches elicit more homogeneous acute physiological responses among individuals, when repeated over time, these uniform responses may manifest as more homogeneous chronic adaptations thereby reducing response variability. Changes in cardiorespiratory fitness (CRF) in response to endurance training (ET) exhibit large variations, possibly due to a multitude of biological and methodological factors. It is acknowledged that ∼20% of individuals may not achieve meaningful increases in CRF in response to ET. Genetics, the most potent biological contributor, has been shown to explain ∼50% of response variability, whilst age, sex and baseline CRF appear to explain a smaller proportion. Methodological factors represent the characteristics of the ET itself, including the type, volume and intensity of exercise, as well as the method used to prescribe and control exercise intensity. Notably, methodological factors are modifiable and, upon manipulation, alter response rates to ET, eliciting increases in CRF regardless of an individual's biological predisposition. Particularly, prescribing exercise intensity relative to a physiological threshold (e.g., ventilatory threshold) is shown to increase CRF response rates compared to when intensity is anchored relative to a maximum physiological value (e.g., maximum heart rate). It is, however, uncertain whether the increased response rates are primarily attributable to reduced response variability, greater mean changes in CRF or both. Future research is warranted to elucidate whether more homogeneous chronic adaptations manifest over time among individuals, as a result of exposure to more homogeneous exercise stimuli elicited by threshold‐based practices. [ABSTRACT FROM AUTHOR]

• BPA decays the neuronal contrast sensitivity in the primary visual cortex of cats. • Such decline in contrast detection begins at the cortical, not subcortical level. • Decreased neuronal activity and increased noise are involved in this dysfunction. • The increased inhibitory innervations contributes the underlying synaptic basis. Contrast sensitivity (CS) is one of the primary fundamental factors determining how well we can see, and it directly influences object recognition. Whether bisphenol-A (BPA, an environmental xenoestrogen) can perturb contrast detection in the visual system has yet to be elucidated. In the present study, we analyzed CS of single neurons in the primary visual cortex (area 17, A17) of cats before and after BPA exposure using a multiple-channel recording technique. The results showed that CS of A17 neurons was markedly depressed with an increased contrast threshold after two hour of intravenous BPA administration, which had a positive correlation with decreased firing rates of A17 neurons. Additionally, responses of these neurons presented an overt increase in the trial-to-trail response variability (a kind of neuronal noise), which could disturb the information-filtering function of single neurons. We also found that neuronal CS in the visual relay station was not disturbed after BPA administration, which rules out the contribution of CS alteration in the optical pathway. Importantly, acute BPA treatment obviously increased the inhibitory innervation to the visual pyramidal neurons. This implies that alteration of intracortical inhibitory regulation contributes to the compromised contrast detection in the visual system after BPA treatment. [ABSTRACT FROM AUTHOR]

Molecular biomarkers, like gene transcripts or enzyme activities, are potentially powerful tools for early warning assessment of pollution. However, a thorough understanding of response and baseline variation is required to distinguish actual effects from pollution. Here, we assess the freshwater mussel Anodonta anatina as a biomarker model species for freshwater ecosystems, by testing responses of six transcriptional (cat, gst, hsp70, hsp90, mt, and sod) and two biochemical (AChE and GST) biomarkers to environmentally relevant Cu water concentrations. Mussels (n = 20), collected from a stream free from point source pollution, were exposed in the laboratory, for 96 h, to Cu treatments (< 0.2 μg/L, 0.77 ± 0.87 μg/L, and 6.3 ± 5.4 μg/L). Gills and digestive glands were extracted and analyzed for transcriptional and biochemical responses. Biological and statistical effect sizes from Cu treatments were in general small (mean log2 fold-change ≤ 0.80 and Cohen's f ≤ 0.69, respectively), and no significant treatment effects were observed. In contrast, four out of eight biomarkers (cat, gst, hsp70, and GST) showed a significant sex:tissue interaction, and additionally one (sod) showed significant overall effects from sex. Specifically, three markers in gills (cat, mt, GST) and one in digestive gland (AChE) displayed significant sex differences, independent of treatment. Results suggest that sex or tissue effects might obscure low-magnitude biomarker responses and potential early warnings. Thus, variation in biomarker baselines and response patterns needs to be further addressed for the future use of A. anatina as a biomarker model species. [ABSTRACT FROM AUTHOR]

• New sustained-selective attention task reveals development divergence in adolescence. • Sustained attention gradually develops from early to late adolescence, and adulthood. • Selective attention is already mature by early adolescence. • Perceptual load enhances selective- but hinders sustained- attention across all ages. • Sustained and selective attention task measures predict attention in the classroom. Despite much research into the development of attention in adolescence, mixed results and between-task differences have precluded clear conclusions regarding the relative early or late maturation of attention abilities. Moreover, although adolescents constantly face the need to pay attention at school, it remains unclear whether laboratory measures of attention can predict their ability to sustain attention focus during lessons. Therefore, here we devised a task that was sensitive to measure both sustained and selective attention and tested whether task measures could predict adolescents' levels of inattention during lessons. In total, 166 adolescents (aged 12–17 years) and 50 adults performed a sustained selective attention task, searching for letter targets while ignoring salient yet entirely irrelevant distractor faces, under different levels of perceptual load—an established determinant of attention in adults. Inattention levels during a just preceding classroom lesson were measured using a novel self-report classroom distractibility checklist. The results established that sustained attention (measured with response variability) continued to develop throughout adolescence across perceptual load levels. In contrast, there was an earlier maturation of the effect of perceptual load on selective attention; load modulation of distractor interference was larger in the early adolescence period compared with later periods. Both distractor interference and response variability were significant unique predictors of distractibility in the classroom, including when controlling for interest in the lesson and cognitive aptitude. Overall, the results demonstrate divergence of development of sustained and selective attention in adolescence and establish both as significant predictors of attention in the important educational setting of school lessons. [ABSTRACT FROM AUTHOR]

• Motor expertise modulates variability in brain function and behavior. • Changes in brain signal complexity may represent a brain mechanism responsible for cognitive functioning. • Motor expertise may be related to differential modulation of brain signal complexity during cognitive control. • Open and closed skill sports may be differentially related to domain-general cognitions. Motor expertise has recently been associated with differences in domain-general cognition. Studies using averaged neurophysiological signals (e.g., event-related potentials) have shown varying degree of expertise-related differences in neural activity. As a result, the precise mechanisms underlying these differences remain to be described. Here we used multiscale entropy analysis (MSE) to investigate whether the complexity of underlying neural systems working in a wide-range time scales can better explain the cognitive characteristics of athletes with different domains of expertise. Behavioral and electroencephalograms (EEG) measures of athletes practicing an interceptive sport (badminton; n = 17) or a static sport (long-distance running; n = 17) were assessed during a flanker task with varying degrees of response conflict. The interceptive sport players showed superior behavioral performance overall on the task relative to the static sport players. Although both groups exhibited greater sample entropy across most time scales in high-conflict relative to low-conflict trials over the parietal site, this effect was only evident at coarser time scales over the midfrontal site for the interceptive sport players. Together, our results suggest that individual differences in motor expertise may be associated with difference in information-processing capacity and information integration during cognitive processing, as demonstrated by differential cognitive modulation of brain signal variability. [ABSTRACT FROM AUTHOR]

Background Statins have shown multiple effects on different renal risk factors such as lowering of total cholesterol (TC) and lowering of urine protein:creatinine ratio (UPCR). We assessed whether these effects of statins vary between individuals, the extent of discordance of treatment effects on both TC and UPCR within an individual, and the association of responses in TC and UPCR with estimated glomerular filtration rate (eGFR) decline. Methods The PLANET I and II (Renal effects of Rosuvastatin and Atorvastatin in Patients Who Have Progressive Renal Disease) trials examined effects of atorvastatin and rosuvastatin on proteinuria and renal function in patients with proteinuria. We post hoc analysed 471 therapy-adherent proteinuric patients from the two trials and assessed the individual variability in UPCR and TC response from 0 to 14 weeks and whether these responses were predictive of eGFR decline during the subsequent 9 months of follow-up. Results UPCR and TC response varied between individuals: mean UPCR response was −1.3% (5th–95th percentile −59.9 to 141.8) and mean TC response was −93.9 mg/dL (−169.1 to −26.9). Out of 471 patients, 123 (26.1%) showed a response in UPCR but not in TC, and 96 (20.4%) showed a response in TC but not in UPCR. eGFR (mL/min/1.73 m2) did not decrease significantly from baseline in both UPCR responders [0.4; 95% confidence interval (CI) −1.6 to 0.9; P = 0.54] and TC responders (0.3; 95% CI −1.8 to 1.1; P = 0.64), whereas UPCR and TC non-responders showed a significant decline in eGFR from baseline (1.8; 95% CI 0.6–3.0; P = 0.004 and 1.7; 95% CI 0.5–2.9; P = 0.007, respectively). A lack of response in both parameters resulted in the fastest rate of eGFR decline (2.1; 95% CI 0.5–3.7; P = 0.01). These findings were not different for rosuvastatin or atorvastatin. Conclusions Statin-induced changes in cholesterol and proteinuria vary between individuals and do not run in parallel within an individual. The initial fall in cholesterol and proteinuria is independently associated with a reduction in eGFR decline. This highlights the importance of monitoring both cholesterol and proteinuria after initiating statin therapy. [ABSTRACT FROM AUTHOR]

While diverging efficacy and inter-individual response variability have repeatedly been reported for paired-associative stimulation (PAS), approaches to overcome these issues are yet lacking. Hence, the aim of the present study was to determine whether response variability could be reduced through the application of an individualized PAS paradigm. Changes of transcranial magnetic stimulation (TMS) elicited motor-evoked potentials (MEP) following different PAS paradigms were assessed in three experimental conditions. According to a within-subjects design, 21 participants received three consecutive PAS paradigms differing with respect to the applied inter-stimulus intervals (ISI) between peripheral nerve stimulation (PNS) and TMS. Based on foregoing considerations, we compared fixed ISI of 25 ms (PAS 25) and 22 ms (PAS 22) to an individualized PAS paradigm accounting for conduction time differences on the single subject level (iPAS). Overall, we did not observe significantly increased post-stimulation MEP magnitudes in any of the three experimental paradigms. Explorative analyses revealed increased inter-individual response variability in case of PAS 25 and PAS 22 compared to higher rates of expected MEP magnitude increases in case of our iPAS paradigm. The findings of our proof-of-concept study points towards a potential association of decreased inter-individual variability with individually selected ISI that account for differences in conduction time. However, as our findings did not reach the significance threshold, our study highlights the issue of intra-individual variability in PAS paradigms. Further replication studies with larger sample sizes and repetitive designs are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Augmentative and alternative communication (AAC) is a tool used by individuals unable to communicate or experience difficulty communicating vocally. Previous research has demonstrated that individuals will vary their communicative responding when reinforcement is delayed and when the response effort to communicate is increased. This study evaluated the effect of adjusting these variables to alter responding of three elementary age individuals with autism spectrum disorder who used AAC. A reversal design allowed for an evaluation of a functional relation between delay to reinforcement, response effort, and communication response allocation. When these parameters were changed, two participants shifted their responding while the third participant maintained his response allocation. This research provides further evidence that altering delay to reinforcement and response effort may aid in moving an individual from an AAC to spoken language. The researchers discuss outcomes in terms of how these variables can be manipulated in practice and the potential for altering other parameters of reinforcement in context of communication training. [ABSTRACT FROM AUTHOR]

Selective attention decreases trial-to-trial variability in cortical auditory-evoked activity. This effect increases over the course of maturation, potentially reflecting the gradual development of selective attention and inhibitory control. Work in adults indicates that music training may alter the development of this neural response characteristic, especially over brain regions associated with executive control: in adult musicians, attention decreases variability in auditory-evoked responses recorded over prefrontal cortex to a greater extent than in nonmusicians. We aimed to determine whether this musician-associated effect emerges during childhood, when selective attention and inhibitory control are under development. We compared cortical auditory-evoked variability to attended and ignored speech streams in musicians and nonmusicians across three age groups: preschoolers, school-aged children and young adults. Results reveal that childhood music training is associated with reduced auditory-evoked response variability recorded over prefrontal cortex during selective auditory attention in school-aged child and adult musicians. Preschoolers, on the other hand, demonstrate no impact of selective attention on cortical response variability and no musician distinctions. This finding is consistent with the gradual emergence of attention during this period and may suggest no pre-existing differences in this attention-related cortical metric between children who undergo music training and those who do not.

Abstract Response variability has been identified as a useful predictor of executive function and performance in non-clinical samples in the Go/NoGo task. The present study explores the utility of reaction time variability (RTV) and EEG measures as predictors of Go/NoGo performance outcomes and ERP component amplitudes. Forty-four young adults had EEG recorded across eyes-closed (EC) and eyes-open (EO) resting states, and during an auditory Go/NoGo task. The 18 individuals with the lowest/highest RTV were assessed for differences in behavioural outcomes. As expected, individuals with high RTV committed more Go/NoGo errors and had smaller Go P3b and NoGo P3a amplitudes, and greater Go Slow Wave positivity, reflecting inefficient decision-making and response control efforts underlying performance. When RTV and EEG measures were modelled as predictors of Go/NoGo responses, RTV and task-related changes in delta were identified as positive predictors of Go SW amplitude; while RTV and prestimulus delta amplitudes negatively predicted NoGo accuracy rates. Prestimulus delta was also found to solely predict Go mean RT and NoGo SW negativity; effects that were independent of RTV. As delta has been implicated in attention-related mechanisms, these findings suggest that inadequate attention and task engagement underpin the variability in Go/NoGo performance. Highlights • Reaction time variability (RTV) correlated negatively with response accuracy rates • The Go/NoGo ERPs of individuals with low vs. high RTV were assessed • RTV predicted P3b, P3a, and SW amplitudes, marking response control efforts • RTV and task-related delta change positively predicted Go SW amplitude • RTV and prestimulus delta negatively predicted NoGo accuracy rates [ABSTRACT FROM AUTHOR]

Improving bacterial nitrogen fixation in grain legumes is central to sustainable intensification of agriculture in sub-Saharan Africa. In the case of soyabean, two main approaches have been pursued: first, promiscuous varieties were developed to form effective symbiosis with locally abundant nitrogen fixing bacteria. Second, inoculation with elite bacterial strains is being promoted. Analyses of the success of these approaches in tropical smallholder systems are scarce. It is unclear how current promiscuous and non-promiscuous soyabean varieties perform in inoculated and uninoculated fields, and the extent of variation in inoculation response across regions and environmental conditions remains to be determined. We present an analysis of on-farm yields and inoculation responses across ten countries in Sub Saharan Africa, including both promiscuous and non-promiscuous varieties. By combining data from a core set of replicated on-farm trials with that from a large number of farmer-managed try-outs, we study the potential for inoculation to increase yields in both variety types and evaluate the magnitude and variability of response. Average yields were estimated to be 1343 and 1227 kg/ha with and without inoculation respectively. Inoculation response varied widely between trials and locations, with no clear spatial patterns at larger scales and without evidence that this variation could be explained by yield constraints or environmental conditions. On average, specific varieties had similar uninoculated yields, while responding more strongly to inoculation. Side-by side comparisons revealed that stronger responses were observed at sites where promiscuous varieties had superior uninoculated yields, suggesting the availability of compatible, effective bacteria as a yield limiting factor and as a determinant of the magnitude of inoculation response. [ABSTRACT FROM AUTHOR]

We evaluated the effects of lag schedules of reinforcement and functional communication training (FCT) on mand variability and problem behavior in two children with autism spectrum disorder. Specifically, we implemented FCT with increasing lag schedules and compared its effects on problem behavior with baseline conditions. The results showed that both participants exhibited low rates of problem behavior during treatment relative to baseline during and following schedule thinning (up to a Lag 5 schedule arrangement). Variable and total mands remained high during schedule thinning. With one participant, variable manding persisted when the value of the lag schedule was reduced to zero. The current results are discussed in terms of implications for training multiple mand topographies during FCT for the potential prevention and/or mitigation of clinical relapse during challenges to treatment. [ABSTRACT FROM AUTHOR]

Children with autism spectrum disorder and other developmental disabilities often exhibit invariant responding (i.e., restricted behavioral repertoires), deficits in communication, and challenging behavior. Approaches demonstrated in the basic and applied literature to increase response variability include extinction, lag schedules of reinforcement, and percentile schedules of reinforcement. Results of basic studies have also indicated that delays to reinforcement often produce increases in response variability. The purpose of the current study was to evaluate the effects of a delay to reinforcement on the variability of communication responses during functional communication training with individuals with developmental disabilities and histories of engaging in challenging behavior. Results indicated that delays to reinforcement increased mand variability with all four participants with variable effects on challenging behavior across participants. [ABSTRACT FROM AUTHOR]

ADHD is characterized by increased intra-individual variability in response times during the performance of cognitive tasks. However, little is known about developmental changes in intra-individual variability, and how these changes relate to cognitive performance. Twenty subjects with ADHD aged 7–24 years and 20 age-matched, typically developing controls participated in an fMRI-scan while they performed a go-no-go task. We fit an ex-Gaussian distribution on the response distribution to objectively separate extremely slow responses, related to lapses of attention, from variability on fast responses. We assessed developmental changes in these intra-individual variability measures, and investigated their relation to no-go performance. Results show that the ex-Gaussian measures were better predictors of no-go performance than traditional measures of reaction time. Furthermore, we found between-group differences in the change in ex-Gaussian parameters with age, and their relation to task performance: subjects with ADHD showed age-related decreases in their variability on fast responses (sigma), but not in lapses of attention (tau), whereas control subjects showed a decrease in both measures of variability. For control subjects, but not subjects with ADHD, this age-related reduction in variability was predictive of task performance. This group difference was reflected in neural activation: for typically developing subjects, the age-related decrease in intra-individual variability on fast responses (sigma) predicted activity in the dorsal anterior cingulate gyrus (dACG), whereas for subjects with ADHD, activity in this region was related to improved no-go performance with age, but not to intra-individual variability. These data show that using more sophisticated measures of intra-individual variability allows the capturing of the dynamics of task performance and associated neural changes not permitted by more traditional measures.

The left dorsolateral prefrontal cortex (DLPFC) is involved in encoding and retrieval of episodic memories, and thus, is frequently targeted in non-invasive brain stimulation paradigms, aiming for its functional modulation. Anodal transcranial direct current stimulation (tDCS), that boosts neuronal excitability in stimulated cortical areas, has been found to increase cognitive skills differentially, depending on the initial performance. We hypothesize that the benefit of tDCS on verbal episodic memory can be extrapolated from the participants’ baseline performance. In the present randomized, double-blind, parallel group study, healthy young adults (n = 43) received either real anodal or sham tDCS over their left DLPFC during the encoding phase of a verbal episodic memory task. Forty words were presented visually thrice with immediate vocal retrieval after each block and an additional delayed recall. We conducted a moderation analysis to test the modulating effect of initial episodic memory retrieval, adjusted for primacy and recency effects, on delayed recall under real or sham stimulation. Despite the absence of a significantly beneficial tDCS effect at the group level, we found that the number of remembered midlist words in the first retrieval significantly moderated the stimulation effect in such a way that initially low performers experienced the highest gain from real stimulation. These results suggest that anodal tDCS to the left DLPFC improves memory functions only so far. While only marginal stimulation-induced gains occur in cognitively unimpaired populations, greater stimulation benefits might be expected in individuals with clinically relevant deficiencies in the verbal episodic memory domain.

Cortical activity contributes significantly to the high variability of sensory responses of interconnected pyramidal neurons, which has crucial implications for sensory coding. Yet, largely because of technical limitations of in vivo intracellular recordings, the coupling of a pyramidal neuron's synaptic inputs to the local cortical activity has evaded full understanding. Here we obtained excitatory synaptic conductance (g) measurements from putative pyramidal neurons and local field potential (LFP) recordings from adjacent cortical circuits during visual processing in the turtle whole brain ex vivo preparation. We found a range of g-LFP coupling across neurons. Importantly, for a given neuron, g-LFP coupling increased at stimulus onset and then relaxed toward intermediate values during continued visual stimulation. A model network with clustered connectivity and synaptic depression reproduced both the diversity and the dynamics of g-LFP coupling. In conclusion, these results establish a rich dependence of single-neuron responses on anatomical, synaptic, and emergent network properties. [ABSTRACT FROM AUTHOR]

The article discusses neurocognitive factors of decision-making and response variability to recognize stimulus categories and select between different response alternatives. Topics discussed include cognitive neuroscience to understand how executive functions allow to make decisions, relationship between executive functioning and performance variability at group level and identification of neurophysiology to correlate executive functioning to investigate different cognitive abilities.

The left dorsolateral prefrontal cortex (DLPFC) is involved in encoding and retrieval of episodic memories, and thus, is frequently targeted in non-invasive brain stimulation paradigms, aiming for its functional modulation. Anodal transcranial direct current stimulation (tDCS), that boosts neuronal excitability in stimulated cortical areas, has been found to increase cognitive skills differentially, depending on the initial performance. We hypothesize that the benefit of tDCS on verbal episodic memory can be extrapolated from the participants’ baseline performance. In the present randomized, double-blind, parallel group study, healthy young adults (n = 43) received either real anodal or sham tDCS over their left DLPFC during the encoding phase of a verbal episodic memory task. Forty words were presented visually thrice with immediate vocal retrieval after each block and an additional delayed recall. We conducted a moderation analysis to test the modulating effect of initial episodic memory retrieval, adjusted for primacy and recency effects, on delayed recall under real or sham stimulation. Despite the absence of a significantly beneficial tDCS effect at the group level, we found that the number of remembered midlist words in the first retrieval significantly moderated the stimulation effect in such a way that initially low performers experienced the highest gain from real stimulation. These results suggest that anodal tDCS to the left DLPFC improves memory functions only so far. While only marginal stimulation-induced gains occur in cognitively unimpaired populations, greater stimulation benefits might be expected in individuals with clinically relevant deficiencies in the verbal episodic memory domain. [ABSTRACT FROM AUTHOR]

The linking of microstructure uncertainty with the random variation of material properties at higher scales is of paramount importance in the framework of the stochastic finite element method (SFEM). An efficient computational scheme has been recently proposed by the authors for the determination of mesoscale random fields for the apparent properties and of the RVE size of particle-reinforced composites based on computer-simulated images of their microstructure. The proposed approach exploits the excellent synergy of the extended finite element method (XFEM) and Monte Carlo simulation in order to analyze the microstructure models and obtain statistical information (probability distribution, correlation structure) for the apparent properties of the composite in each mesoscale size. In this paper, sample functions of the statistically homogeneous mesoscale random fields are generated using the spectral representation method in conjunction with translation field theory. Moreover, micro-mechanically consistent (lower and upper) bounds on the macroscopic response of composite structures are computed in the framework of SFEM. Useful conclusions are derived regarding the effect of particle/matrix stiffness ratio on the probabilistic characteristics of the mesoscale random fields as well as the influence of mesoscale size on the response variability. [ABSTRACT FROM AUTHOR]

Aims Albuminuria reduction is essential for renal and cardiovascular protection. We characterized the efficacy of dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, on albuminuria. Secondly, we assessed whether the albuminuria-lowering effect varies among patients, and whether this variability in response is reproducible. Material and methods A double-blind, randomized, placebo controlled crossover trial was conducted. Patients with type 2 diabetes and albumin:creatinine ratio > 100 mg/g on a stable dose of an angiotensin-converting enzyme inhibitor ( ACEi) or angiotensin receptor blocker ( ARB) were enrolled. Patients were assigned to 6-week treatment periods with dapagliflozin 10 mg/d or placebo in random order, separated by 6-weeks wash-out periods. After the 2 treatment periods, half of the patients were re-exposed for 6 weeks to dapagliflozin 10 mg/d. Primary outcome was change in 24-hour urinary albumin excretion rate (24 h UAE). To assess reproducibility in individual albuminuria response, responses from the first and second exposure to dapagliflozin were correlated. Results A total of 33 patients (age, 61 years; female gender, 24.2%; median 24 h UAE, 470 mg/24 h) completed the study. Dapagliflozin, as compared to placebo, reduced 24 h UAE by 36.2% (95% CI, 22.9-47.2; P < .001). Systolic blood pressure fell by 5.2 mm Hg (95% CI, 0.5-10.0) and eGFR by 5.3 (95% CI, 2.7-8.0). All effects were reversible directly after treatment discontinuation. In a subgroup of 15 patients who were exposed twice to dapagliflozin, 24 h UAE responses showed a large variation among individuals: first exposure (range, −76% to +52%) and second exposure (−90% to +95%) and first and second individual response were significantly correlated (r = 0.69 [95% CI, 0.27-0.89]; P < .004). Conclusion Dapagliflozin significantly reduces albuminuria when given as adjunct to ACEi or ARB. The albuminuria response to dapagliflozin markedly varies among patients. This variation is not a random phenomenon, but is reproducible upon re-exposure. These data support personalized therapy approaches to optimize diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Previously reinforced responses can reappear when reinforcement is withdrawn from current responding. This is known as resurgence. Although resurgence of response topography, spacing, and patterns over time has been demonstrated, there is no evidence of resurgence of response duration. This experiment explored resurgence of response duration in humans. In Phase 1 a multiple schedule of reinforcement with two components was used. In each component a chained variable-interval 30 s, variable-ratio 3 schedule was implemented. In the terminal link of the chained schedule, response durations between 0.1 and 0.5 s were reinforced during one component, and between 2 and 8 s in the other component. In Phase 2, response requirement during the terminal link of the chained schedule was inverted between components relative to Phase 1. In Phase 3 the chained schedule was changed to a variable-interval 30-s, extinction 30 s. Resurgence of the durations trained during Phase 1 was observed. It was concluded that duration is a response dimension that reappears during extinction. [ABSTRACT FROM AUTHOR]

Response variability is sensitive to antecedent and consequent manipulations. Researchers have investigated inducement, direct production through reinforcement, and stimulus control of response variability. Recently, researchers have shown that lag reinforcement schedules reliably increase variability but may also produce higher-order stereotypy. There has been limited investigation of appropriate variability levels and alternation between repetition and variation. In a three-part study, we evaluated levels of variability across a group of children, the effects of various procedures on producing response variability and novelty, and the use of schedule-correlated stimuli for producing rapid alternation between repetition and variation. In Study 1, there was a nearly bimodal distribution of children emitting either low or high variability. In Study 2, for most children, fixed lag 4 and variable lag 4 schedules produced the highest levels of variability and novelty. In Study 3, responding was brought under control of schedule-correlated stimuli, allowing for rapid alternation between repetition and variation. [ABSTRACT FROM AUTHOR]

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There is evidence that noninvasive brain stimulation (NIBS), and especially transcranial direct current stimulation (tDCS), can improve some cognitive functions, at least temporarily. However, as the improvement only applies to some "lucky" people, it may raise ethical, social and legal issues related to fairness in selective contexts (exams, competitions, job interviews). In this regard, an important element tends to be overlooked: the variability in individual response to tDCS in particular. If intensive study or practice and massive doses of chemical enhancers can have slightly different effects over different people, tDCS can sometimes be completely ineffective. The variability in individual response, if tDCS were widely used, could add to the already present natural inequalities between people, or even create new ones, leaving some in a disadvantaged condition. The discussion of the various ethical, social and legal consequences of different individual responses to tDCS might also address a potential indirect intervention by the State. In fact, if NIBS were to be widespread in competitive contexts, those who do not benefit from tDCS would be disadvantaged compared to those able to enhance their skills thanks to neuromodulation technologies. The most disadvantaged people for their lower response to tDCS could then acquire the right to receive and use free and safe cognitive enhancing drugs or other forms of bettering cognitive skills and functions, so as to reduce the gap between them and those who respond well to tDCS, in the light of the principle of equal opportunity. [ABSTRACT FROM AUTHOR]

Adolescence is a period of learning, exploration, and continuous adaptation to fluctuating environments. Response variability during adolescence is an important, understudied, and developmentally appropriate behavior. The purpose of this study was to identify the association between performance on a dynamic risky decision making task and white matter microstructure in a sample of 48 adolescents (14-16 years). Individuals with the greatest response variability on the task obtained the widest range of experience with potential outcomes to risky choice. When compared with their more behaviorally consistent peers, adolescents with greater response variability rated real-world examples of risk taking behaviors as less risky via self-report. Tract-Based Spatial Statistics (TBSS) were used to examine fractional anisotropy (FA) and mean diffusivity (MD). Greater FA in long-range, late-maturing tracts was associated with higher response variability. Greater FA and lower MD were associated with lower riskiness ratings of real-world risky behaviors. Results suggest that response variability and lower perceived risk attitudes of real-world risk are supported by neural maturation in adolescents. [ABSTRACT FROM AUTHOR]