New perspectives in the echocardiographic hemodynamics multiparametric assessment of patients with heart failure.

International Guidelines consider left ventricular ejection fraction (LVEF) as an important parameter to categorize patients with heart failure (HF) and to define recommended treatments in clinical practice. However, LVEF has some technical and clinical limitations, being derived from geometric assumptions and is unable to evaluate intrinsic myocardial function and LV filling pressure (LVFP). Moreover, it has been shown to fail to predict clinical outcome in patients with end-stage HF. The analysis of LV antegrade flow derived from pulsed-wave Doppler (stroke volume index, stroke distance, cardiac output, and cardiac index) and non-invasive evaluation of LVFP have demonstrated some advantages and prognostic implications in HF patients. Speckle tracking echocardiography (STE) is able to unmask intrinsic myocardial systolic dysfunction in HF patients, particularly in those with LV preserved EF, hence allowing analysis of LV, right ventricular and left atrial (LA) intrinsic myocardial function (global peak atrial LS, (PALS)). Global PALS has been proven a reliable index of LVFP which could fill the gaps "gray zone" in the previous Guidelines algorithm for the assessment of LV diastolic dysfunction and LVFP, being added to the latest European Association of Cardiovascular Imaging Consensus document for the use of multimodality imaging in evaluating HFpEF. The aim of this review is to highlight the importance of the hemodynamics multiparametric approach of assessing myocardial function (from LVFP to stroke volume) in patients with HF, thus overcoming the limitations of LVEF.

The HIV Empowering Adults' Decisions to Share: UK/Uganda (HEADS-UP) Study-A Randomised Feasibility Trial of an HIV Disclosure Intervention for Young Adults with Perinatally Acquired HIV.

Young adults with perinatally acquired HIV (PAH) face numerous challenges, including antiretroviral therapy (ART) adherence, managing onward HIV transmission risks and maintaining wellbeing. Sharing one's HIV status with others (onward HIV disclosure) may assist with these challenges but this is difficult. We developed and tested the feasibility of an intervention to help HIV status sharing decision-making for young adults with PAH. The study used a randomised parallel group feasibility design with 18-25-year-olds in Uganda and 18-29 year-olds in the UK. Participants were randomly assigned to intervention or standard of care (SOC) condition. The intervention consisted of four sessions (3 group, 1 individual) with follow-up support, delivered in person in Uganda and remotely in the UK. Assessments were carried out at: Pre-intervention /baseline; Post-intervention (intervention group only); Six-month follow-up. 142 participants were recruited (94 Uganda, 48 UK; 89 female, 53 male). At six-month follow-up, 92/94 (98%) participants were retained in Uganda, 25/48 (52%) in the UK. Multivariate analysis of combined data from both countries, showed a non-significant effect of intervention condition on HIV disclosure cognitions and affect (p = 0.08) and HIV disclosure intention (p = 0.09). There was a significant intervention effect on well-being (p = 0.005). This study addressed important gaps in understanding acceptable and feasible ways of delivering HIV status sharing support for young people living with PAH across two very different settings. The intervention was acceptable in both countries and feasible in Uganda. In the UK, retention may have been affected by its remote delivery.Trial registration: ISRCTN Registry, ISRCTN31852047, Registered on 21 January 2019.

Different extrapolation of moving object locations in perception, smooth pursuit, and saccades.

The ability to accurately perceive and track moving objects is crucial for many everyday activities. In this study, we use a "double-drift stimulus" to explore the processing of visual motion signals that underlie perception, pursuit, and saccade responses to a moving object. Participants were presented with peripheral moving apertures filled with noise that either drifted orthogonally to the aperture's direction or had no net motion. Participants were asked to saccade to and track these targets with their gaze as soon as they appeared and then to report their direction. In the trials with internal motion, the target disappeared at saccade onset so that the first 100 ms of the postsaccadic pursuit response was driven uniquely by peripheral information gathered before saccade onset. This provided independent measures of perceptual, pursuit, and saccadic responses to the double-drift stimulus on a trial-by-trial basis. Our analysis revealed systematic differences between saccadic responses, on one hand, and perceptual and pursuit responses, on the other. These differences are unlikely to be caused by differences in the processing of motion signals because both saccades and pursuits seem to rely on shared target position and velocity information. We conclude that our results are instead due to a difference in how the processing mechanisms underlying perception, pursuit, and saccades combine motor signals with target position. These findings advance our understanding of the mechanisms underlying dissociation in visual processing between perception and eye movements.

The social roots of self development: from a bodily to an intellectual interpersonal dialogue.

In this paper, we propose that interpersonal bodily interactions represent a fertile ground in which the bodily and psychological self is developed, gradually allowing for forms of more abstract and disembodied interactions. We start by focusing on how early infant-caregiver bodily interactions play a crucial role in shaping the boundaries of the self but also in learning to predict others' behavior. We then explore the social function of the sense of touch in the entire life span, highlighting its role in promoting physical and psychological well-being by supporting positive interpersonal exchanges. We go on by introducing the concept of implicit theory of mind, as the early ability to interpret others' intentions, possibly grounded in infant-caregiver bodily exchanges (embodied practices). In the following part, we consider so-called higher level forms of social interaction: intellectual exchanges among individuals. In this regard, we defend the view that, beside the apparent private dimension of "thinking abstractly", using abstract concepts is intrinsically a social process, as it entails the re-enactment of the internalized dialogue through which we acquired the concepts in the first place. Finally, we describe how the hypothesis of "dialectical attunement" may explain the development of abstract thinking: to effectively transform the world according to their survival needs, individuals co-construct structured concepts of it; by doing so, humans fundamentally transform not merely the world they are being in, but their being in the world.

Detection of myocardial fibrosis by speckle-tracking echocardiography: from prediction to clinical applications.

Myocardial fibrosis (MF) represents the underlying pathologic condition of many cardiac disease, leading to cardiac dysfunction and heart failure (HF). Biopsy studies have shown the presence of MF in patients with decompensating HF despite apparently normal cardiac function. In fact, basic indices of left ventricular (LV) function, such as LV ejection fraction (EF), fail to recognize subtle LV dysfunction caused by MF. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is currently recognized as the gold standard imaging investigation for the detection of focal and diffuse cardiac chambers MF; however, its use is limited by its availability and the use of contrast agents, while echocardiography remains the first level cardiac imaging technique due to its low cost, portability and high accessibility. Advanced echocardiographic techniques, above all speckle-tracking echocardiography (STE), have demonstrated reliability for early detection of structural myocardial abnormalities and for the prediction of prognosis in acute and chronic HF. Myocardial strain of both ventricles and also left atrium has been shown to correlate with the degree of MF, providing useful prognostic information in several diseases, such as HF, cardiomyopathies and valvular heart disease. This paper aims to provide an overview of the pathophysiology of MF and the clinical application of STE for the prediction of left and right heart chambers MF in HF patients.

Trust and childhood maltreatment: evidence of bias in appraisal of unfamiliar faces.

BACKGROUND: Child maltreatment is associated with poorer social functioning and increased risk of mental health problems in adolescence and adulthood, but the processes underlying these associations remain unclear. Although crucial for establishing and maintaining relationships, trust judgements have not been experimentally investigated in children who have experienced abuse and neglect. METHODS: A community-based sample of 75 children aged 8-16 years with maltreatment documented on the basis of social services records, and a group of 70 peers matched on age, gender, cognitive ability, socioeconomic status, and ethnicity took part in the study. Children completed a trustworthiness face-judgement task in which they appraised the trustworthiness of unfamiliar facial stimuli varying along a computationally modelled trustworthiness dimension. RESULTS: In line with clinical observations that childhood maltreatment is associated with an atypical pattern of trust processing, children with maltreatment experience were significantly less likely than their peers to rate unfamiliar faces as trustworthy. Moreover, they were more variable in their trust attributions than their peers. CONCLUSIONS: The study provides compelling experimental evidence that children with documented maltreatment perceive others as less trustworthy than their peers and are less consistent in their estimates of trustworthiness in others. Over time, alterations in trust processing may disrupt the development of social bonds and contribute to 'social thinning' (a reduction in the extent and quality of social relationships), leaving children more vulnerable to environmental stressors, increasing risk of mental health difficulties.

War-related trauma linked to increased sustained attention to threat in children.

Experiences of war and displacement can have profound effects on children's affective development and mental health, although the mechanism(s) underlying these effects remain unknown. This study investigated the link between early adversity and attention to affective stimuli using a free-viewing eye-tracking paradigm with Syrian refugee (n = 31, Mage  = 9.55, 12 female) and Jordanian non-refugee (n = 55, Mage  = 9.98, 30 female) children living in Jordan (March 2020). Questionnaires assessed PTSD, anxiety/depression, insecurity, distress, and trauma. Refugee children showed greater initial avoidance of angry and happy faces compared to non-refugee children, and higher trauma exposure was linked to increased sustained attention to angry stimuli. These findings suggest that war-related trauma may have differential effects on the early and later stages of affective processing in refugee children.

Left atrial myocardial intrinsic function remodeling response to repair of primary mitral regurgitation.

Severe mitral regurgitation (MR) is a common valve disease which is associated with high mortality, if only managed medically. MR produces chronic and progressive volume overload with left atrial (LA) and left ventricular (LV) dilatation and dysfunction, atrial fibrillation (AF) and eventually myocardial fibrosis, irrespective of ejection fraction (EF). Surgical correction (mitral valve repair) of MR removes the volume overload, hence unmasks pre-operative LV structure and function disturbances, including reduced EF and global longitudinal and circumferential strain, as well as LA volume and strain. This review aims at describing LA remodeling before and after surgical repair.

Gain control of saccadic eye movements is probabilistic.

Saccades are rapid eye movements that orient the visual axis toward objects of interest to allow their processing by the central, high-acuity retina. Our ability to collect visual information efficiently relies on saccadic accuracy, which is limited by a combination of uncertainty in the location of the target and motor noise. It has been observed that saccades have a systematic tendency to fall short of their intended targets, and it has been suggested that this bias originates from a cost function that overly penalizes hypermetric errors. Here, we tested this hypothesis by systematically manipulating the positional uncertainty of saccadic targets. We found that increasing uncertainty produced not only a larger spread of the saccadic endpoints but also more hypometric errors and a systematic bias toward the average of target locations in a given block, revealing that prior knowledge was integrated into saccadic planning. Moreover, by examining how variability and bias covaried across conditions, we estimated the asymmetry of the cost function and found that it was related to individual differences in the additional time needed to program secondary saccades for correcting hypermetric errors, relative to hypometric ones. Taken together, these findings reveal that the saccadic system uses a probabilistic-Bayesian control strategy to compensate for uncertainty in a statistically principled way and to minimize the expected cost of saccadic errors.

Exploring the frame effect.

Probes flashed within a moving frame are dramatically displaced (Özkan, Anstis, 't Hart, Wexler, & Cavanagh, 2021; Wong & Mack, 1981). The effect is much larger than that seen on static or moving probes (induced motion, Duncker, 1929; Wallach, Bacon, & Schulman, 1978). These flashed probes are often perceived with the separation they have in frame coordinates-a 100% effect (Özkan et al., 2021). Here, we explore this frame effect on flashed tests with several versions of the standard stimulus. We find that the frame effect holds for smoothly or abruptly displacing frames, even when the frame changed shape or orientation between the end points of its travel. The path could be nonlinear, even circular. The effect was driven by perceived not physical motion. When there were competing overlapping frames, the effect was determined by which frame was attended. There were a number of constraints that limited the effect. A static anchor near the flashes suppressed the effect but an extended static texture did not. If the probes were continuous rather than flashed, the effect was abolished. The observational reports of 30 online participants suggest that the frame effect is robust to many variations in its shape and path and leads to a perception of flashed tests in their locations relative to the frame as if the frame were stationary. Our results highlight the role of frame continuity and of the grouping of the flashes with the frame in generating the frame effect.

Smooth pursuit operates over perceived not physical positions of the double-drift stimulus.

The double-drift illusion produces a large deviation in perceived direction that strongly dissociates physical position from perceived position. Surprisingly, saccades do not seem to be affected by the illusion (Lisi & Cavanagh, 2015). When targeting a double-drift stimulus, the saccade system is driven by retinal rather than perceived position. Here, using paired double-drift targets, we test whether the smooth pursuit system is driven by perceived or physical position. Participants (n = 7) smoothly pursued the inferred midpoint (Steinbach, 1976) between two horizontally aligned Gabor patches that were separated by 20° and moving on parallel, oblique paths. On the first half of each trial, the Gabors' internal textures were static while both drifted obliquely downward. On the second half of each trial, while the envelope moved obliquely upward, the internal texture drifted orthogonally to the envelope's motion, producing a large perceived deviation from the downward path even though the upward and downward trajectories always followed the same physical path but in opposite directions. We find that smooth pursuit eye movements accurately followed the nonillusory downward path of the midpoint between the two Gabors, but then followed the illusory rather than the physical trajectory on the upward return. Thus, virtual targets for smooth pursuit are derived from perceived rather than retinal coordinates.

Perceiving Locations of Moving Objects Across Eyeblinks.

Eyeblinks cause disruption of visual input that generally goes unnoticed. It is thought that the brain uses active suppression to prevent awareness of the gaps, but it is unclear how suppression would affect the perception of dynamic events when visual input changes across the blink. Here, we addressed this question by studying the perception of moving objects around eyeblinks. In Experiment 1 (N = 16), we observed that when motion terminates during a blink, the last perceived position is shifted forward from its actual last position. In Experiment 2 (N = 8), we found that motion trajectories were perceived as more continuous when the object jumped backward during the blink, canceling a fraction of the space that it traveled. This suggests subjective underestimation of blink duration. These results reveal the strategies used by the visual system to compensate for disruptions and maintain perceptual continuity: Time elapsed during eyeblinks is perceptually compressed and filled with extrapolated information.

Memory-guided saccades show effect of a perceptual illusion whereas visually guided saccades do not.

The double-drift stimulus (a drifting Gabor with orthogonal internal motion) generates a large discrepancy between its physical and perceived path. Surprisingly, saccades directed to the double-drift stimulus land along the physical, and not perceived, path (Lisi M, Cavanagh P. Curr Biol 25: 2535-2540, 2015). We asked whether memory-guided saccades exhibited the same dissociation from perception. Participants were asked to keep their gaze centered on a fixation dot while the double-drift stimulus moved back and forth on a linear path in the periphery. The offset of the fixation was the go signal to make a saccade to the target. In the visually guided saccade condition, the Gabor kept moving on its trajectory after the go signal but was removed once the saccade began. In the memory conditions, the Gabor disappeared before or at the same time as the go-signal (0- to 1,000-ms delay) and participants made a saccade to its remembered location. The results showed that visually guided saccades again targeted the physical rather than the perceived location. However, memory saccades, even with 0-ms delay, had landing positions shifted toward the perceived location. Our result shows that memory- and visually guided saccades are based on different spatial information. NEW & NOTEWORTHY We compared the effect of a perceptual illusion on two types of saccades, visually guided vs. memory-guided saccades, and found that whereas visually guided saccades were almost unaffected by the perceptual illusion, memory-guided saccades exhibited a strong effect of the illusion. Our result is the first evidence in the literature to show that visually and memory-guided saccades use different spatial representations.

Cue-target contingencies modulate voluntary orienting of spatial attention: dissociable effects for speed and accuracy.

Voluntary orienting of spatial attention is typically investigated by visually presented directional cues, which are called predictive when they indicate where the target is more likely to appear. In this study, we investigated the nature of the potential link between cue predictivity (the proportion of valid trials) and the strength of the resulting covert orienting of attention. Participants judged the orientation of a unilateral Gabor grating preceded by a centrally presented, non-directional, color cue, arbitrarily prompting a leftwards or rightwards shift of attention. Unknown to them, cue predictivity was manipulated across blocks, whereby the cue was only predictive for either the first or the second half of the experiment. Our results show that the cueing effects were strongly influenced by the change in predictivity. This influence differently emerged in response speed and accuracy. The speed difference between valid and invalid trials was significantly larger when cues were predictive, and the amplitude of this effect was modulated at the single trial level by the recent trial history. Complementary to these findings, accuracy revealed a robust effect of block history and also a different time-course compared with speed, as if it mainly mirrored voluntary processes. These findings, obtained with a new manipulation and using arbitrary non-directional cueing, demonstrate that cue-target contingencies strongly modulate the way attention is deployed in space.

Mitral regurgitation severity correlates with symptoms and extent of left atrial dysfunction: Effect of mitral valve repair.

PURPOSE: We aimed to assess the relationship between mitral regurgitation (MR) severity, symptoms, and left atrial (LA) structure and function, before and after mitral valve repair (MVR). METHODS: Global peak atrial longitudinal strain (PALS) was evaluated in 37 patients with severe symptomatic MR and preserved left ventricular (LV) ejection fraction (60.4% ± 4.6%) before and 3 months after MVR and was compared with values from 30 age- and gender-matched controls. RESULTS: Before surgery, PALS was worse in patients than in controls and indexed LA volume was greater (P < .0001 for both). After MVR, PALS deteriorated further and LA volume decreased (P = .001 and P = .05, respectively) as did LV ejection fraction, longitudinal strain (P = .05 and P < .001, respectively), and LV mass (P < .0001). Before surgery, LA volume correlated modestly with LV end-diastolic volume (R = 0.51; P = .01); effective regurgitant orifice area (EROA) correlated with PALS (R = -0.69, P < .001) and with LV longitudinal strain (R = 0.54, P = .01), and New York Heart Association class correlated with PALS (R = -0.69, P < .001), EROA (R = 0.69, P < .001), and LA volume (R = 0.51, P = .04). LA volume was the strongest predictor of global PALS reduction (P < .001), whereas global PALS was the main predictor of postoperative atrial fibrillation (AF) (P < .001). CONCLUSIONS: In patients with severe MR, EROA correlate with symptoms and LA PALS, which itself predicts the occurrence of postoperative AF. Strain values were superior to 2D data for the prediction of postoperative AF.

Different spatial representations guide eye and hand movements.

Our visual system allows us to localize objects in the world and plan motor actions toward them. We have recently shown that the localization of moving objects differs between perception and saccadic eye movements (Lisi & Cavanagh, 2015), suggesting different localization mechanisms for perception and action. This finding, however, could reflect a unique feature of the saccade system rather than a general dissociation between perception and action. To disentangle these hypotheses, we compared object localization between saccades and hand movements. We flashed brief targets on top of double-drift stimuli (moving Gabors with the internal pattern drifting orthogonally to their displacement, inducing large distortions in perceived location and direction) and asked participants to point or make saccades to them. We found a surprising difference between the two types of movements: Although saccades targeted the physical location of the flashes, pointing movements were strongly biased toward the perceived location (about 63% of the perceptual illusion). The same bias was found when pointing movements were made in open-loop conditions (without vision of the hand). These results indicate that dissociations are present between different types of actions (not only between action and perception) and that visual processing for saccadic eye movements differs from that for other actions. Because the position bias in the double-drift stimulus depends on a persisting influence of past sensory signals, we suggest that spatial maps for saccades might reflect only recent, short-lived signals, and the spatial representations supporting conscious perception and hand movements integrate visual input over longer temporal intervals.

Left Ventricular Deformation and Myocardial Fibrosis in Patients With Advanced Heart Failure Requiring Transplantation.

PURPOSE: To evaluate potential relationships between different components of left ventricular (LV) function and histopathological evidence for myocardial fibrosis in patients undergoing heart transplantation. METHODS: The study population included patients with advanced heart failure, referred for an echocardiographic examination before heart transplantation. Traditional LV function measurements and global longitudinal strain (GLS) by speckle tracking echocardiography, averaging all LV segments in 4-, 2-, and 3-chamber views were obtained in all subjects. LV tissue samples were obtained from all patients who underwent heart transplantation. Myocardial fibrosis was assessed using Masson's staining. RESULTS: Of 106 patients referred for cardiac transplantation, 47 underwent cardiac transplantation and were enrolled in the study. LV myocardial fibrosis and its grade strongly correlated with GLS (r = 0.75, P = .0001), modestly with global circumferential strain and LV torsion (r = 0.61, P = .001 and r = 0.52, P = .01, respectively) and weakly with mitral S' wave (r = -0.41; P = .01) and mitral annular plane systolic excursion (r = -0.35; P = .05) but did not correlate with LV ejection fraction (r = -0.12; P = NS). GLS had the strongest accuracy for detecting LV fibrosis (area under the curve, 0.92). None of the echo parameters correlated with patient's exercise capacity. CONCLUSION: Global longitudinal strain is the most accurate LV global function measure that correlates with the extent of myocardial fibrosis in patients with advanced systolic HF requiring heart transplantation.

Voluntary eye movements direct attention on the mental number space.

Growing evidence suggests that orienting visual attention in space can influence the processing of numerical magnitude, with leftward orienting speeding up the processing of small numbers relative to larger ones and the converse for rightward orienting. The manipulation of eye movements is a convenient way to direct visuospatial attention, but several aspects of the complex relationship between eye movements, attention orienting and number processing remain unexplored. In a previous study, we observed that inducing involuntary, reflexive eye movements by means of optokinetic stimulation affected number processing only when numerical magnitude was task relevant (i.e., during magnitude comparison, but not during parity judgment; Ranzini et al., in J Cogn Psychol 27, 459-470, (2015). Here, we investigated whether processing of task-irrelevant numerical magnitude can be modulated by voluntary eye movements, and whether the type of eye movements (smooth pursuit vs. saccades) would influence this interaction. Participants tracked with their gaze a dot while listening to a digit. The numerical task was to indicate whether the digit was odd or even through non-spatial, verbal responses. The dot could move leftward or rightward either continuously, allowing tracking by smooth pursuit eye movements, or in discrete steps across a series of adjacent locations, triggering a sequence of saccades. Both smooth pursuit and saccadic eye movements similarly affected number processing and modulated response times for large numbers as a function of direction of motion. These findings suggest that voluntary eye movements redirect attention in mental number space and highlight that eye movements should play a key factor in the investigation of number-space interactions.

Correlation of Left Atrial Strain and Doppler Measurements with Invasive Measurement of Left Ventricular End-Diastolic Pressure in Patients Stratified for Different Values of Ejection Fraction.

BACKGROUND: This study aimed at exploring the correlation of left atrial longitudinal function by speckle tracking echocardiography (left atrial strain) and Doppler measurements (E/E' ratio) with direct measurements of left ventricular (LV) end-diastolic pressure (LVEDP) in patients stratified for different values of ejection fraction. METHODS: The study population was 80 stable patients with sinus rhythm undergoing cardiac catheterization. This population was selected in order to have four groups of 20 patients each with different LV ejection fraction (>55%, 45-54%, 30-44%, and <30%). LVEDP was obtained during cardiac catheterization; peak atrial longitudinal strain (PALS) and mean E/E' ratio were measured in all subjects. RESULTS: Similar correlations with LVEDP of global PALS and E/E' ratio were recorded in patients with preserved (r = -0.79 vs. r = 0.72, respectively; P < 0.0001 for both) or mildly reduced ejection fraction (r = -0.75 vs. r = 0.73, respectively; P < 0.0001 for both). A closer correlation of global PALS compared to E/E' ratio was evident in patients with moderate (r = -0.78 P < 0.0001; vs. r = 0.47 P = 0.01, respectively) and severe reduction (r = -0.74 P < 0.0001; vs. r = 0.19 ns, respectively) of LV ejection fraction. In multivariate analysis of all measurements, global PALS emerged as a determinant of the LVEDP, independent on other confounding factors and, with the cutoff value of 18.0% presented the best diagnostic accuracy to predict a LVDP above 12 mmHg (AUC 0.87). CONCLUSIONS: In patients with preserved or mildly reduced LV ejection fraction, global PALS and mean E/E' ratio presented good correlations with LVEDP. In patients with moderate or severe reduction of ejection fraction, E/E' ratio correlated poorly with invasively obtained LV filling pressures. Global PALS provided an overall better estimation of LV filling pressures.