Manifesto for a European research network into Problematic Usage of the Internet.

The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.

Correlation between cognitive deficits and Abeta deposits in transgenic APP+PS1 mice.

Doubly transgenic mAPP+mPS1 mice (15-16 months) had impaired cognitive function in a spatial learning and memory task that combined features of a water maze and a radial arm maze. Nontransgenic mice learned a new platform location each day during 4 consecutive acquisition trials, and exhibited memory for this location in a retention trial administered 30 min later. In contrast, transgenic mice were, on average, unable to improve their performance in finding the hidden platform over trials. The cognitive performance of individual mice within the transgenic group were inversely related to the amount of Abeta deposited in the frontal cortex and hippocampus. These findings imply that mAPP+mPS1 transgenic mice develop deficits in cognitive ability as Abeta deposits increase. These data argue that radial arm water maze testing of doubly transgenic mice may be a useful behavioral endpoint in evaluating the functional consequences of potential AD therapies, especially those designed to reduce Abeta load.

Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes.

This study provides a comprehensive behavioral characterization during aging of transgenic mice bearing both presenilin-1 (PS1) and amyloid precursor protein (APP(670,671)) mutations. Doubly transgenic mice and non-transgenic controls were evaluated at ages wherein beta-amyloid (Abeta) neuropathology in APP+PS1 mice is low (5-7 months) or very extensive (15-17 months). Progressive cognitive impairment was observed in transgenic mice for both water maze acquisition and radial arm water maze working memory. However, transgenicity did not affect Y-maze alternations, circular platform performance, standard water maze retention, or visible platform recognition at either age, nor did transgenicity affect anxiety levels in elevated plus-maze testing. In sensorimotor tasks, transgenic mice showed a progressive increase in open field activity, a progressive impairment in string agility, and an early-onset impairment in balance beam. None of these sensorimotor changes appeared to be contributory to any cognitive impairments observed, however. Non-transgenic mice showed no progressive behavioral change in any measure evaluated. Given the age-related cognitive impairments presently observed in APP+PS1 transgenic mice and their progressive Abeta deposition/neuroinflammation, Abeta neuropathology could be involved in these progressive cognitive impairments. As such, the APP+PS1 transgenic mouse offers unique opportunities to develop therapeutics to treat or prevent Alzheimer's Disease through modulation of Abeta deposition/neuroinflammation.

Left and right atrial volume by freehand three-dimensional echocardiography: in vivo validation using magnetic resonance imaging.

INTRODUCTION: Measurement of left and right atrial size is important for the management of arrhythmias, valvular and congenital heart disease. We have demonstrated that freehand three-dimensional (3D) echocardiography is more accurate and reproducible than two-dimensional (2D) echocardiography for measurement of left ventricular mass and volume. However, no prior study has validated the accuracy of freehand 3D for the determination of left or right atrial volume. METHODS: End-systolic (maximum) left and right atrial volumes were determined in 21 volunteer patients and normal subjects by one, two, and freehand 3D transthoracic echocardiography and compared to volumes obtained by gradient recalled magnetic resonance imaging. Three-dimensional echocardiographic determination of atrial volume was obtained using an acoustic spatial locator, a line-of-intersection display, and a surface reconstruction algorithm. Two-dimensional echocardiographic atrial volumes were obtained from apical biplane images of the left atrium and an apical single plane image of the right atrium using a summation of disks method. One-dimensional (ID) estimates of left atrial volume were determined by cubing the M-mode ID antero-posterior dimension obtained on the parasternal long axis view. RESULTS: An excellent correlation was Obtained between freedhand 3D echocardiography and magnetic resonce imaging (MRI) for the left atrium (r = 0.90, SEE=9.6 ml) and for the right atrium (r = 0.91, SEE = 8.8 ml) with a small bias (left atrium 5.25 ml, right atrium 12.06 ml) and narrow limits of agreement (left atrium 22.14 ml, right atrium 25.54 ml). Two-dimensional echocardiography correlated less well (left atrium r = 0.87, SEE = 10.23 ml, right atrium r = 0.79, SEE = 19.74 ml), and had a higher bias (left atrium 14.46 ml, right atrium 8.99 ml) and larger limits of agreement (left atrium 24.37 ml, right atrium 41.16 ml). One-dimensional estimates of left atrial volume correlated poorly with magnetic resonance determined left atrial volume (r = 0.80, SEE = 6.61 ml) and had unacceptably high bias (45.09 ml) and limits of agreement (35.52 ml). Interobserver variability was lowest for 3D echocardiography (left atrium 7.2 ml, 11%, right atrium 8.7 ml, 16%). CONCLUSIONS: Freehand 3D echocardiography using the line of intersection display for guidance of image positioning and a polyhedral surface reconstruction algorithm is a valid, accurate, reproducible method for determining left and right atrial volume in humans that is comparable to magnetic resonance imaging and is superior to current ID and 2D echocardiographic techniques.

Progressive and gender-dependent cognitive impairment in the APP(SW) transgenic mouse model for Alzheimer's disease.

To determine if early cognitive sensorimotor deficits exist in APP(SW) transgenic mice overexpressing human amyloid precursor protein (APP). Tg+ and Tg- animals at both 3 and 9 months of age (3M and 9M, respectively) were evaluated in a comprehensive battery of measures. The performance of all Tg+ mice at both ages was no different from all Tg- controls in Y-maze alternations, water maze acquisition, passive avoidance, and active avoidance testing. By contrast, results from other tasks revealed substantive cognitive deficits in Tg+ mice that were usually gender-dependent and sometimes progressive in nature. Between 3M and 9M, a progressive impairment was observed in circular platform performance by Tg+ males, as was a progressive deficit in visible platform testing for all Tg+ animals. Other transgenic effects included both impaired water maze retention and circular platform performance in 3M Tg+ females; this later effect was responsible for an overall (males + females) Tg+ deficit in circular platform performance at 3M. Sensorimotor testing revealed several Tg+ effects, most notably an increased activity of Tg+ males in both open field and Y-maze at 3M. Significant correlations between a number of behavioral measures were observed, although factor analysis suggests that each task measured components of sensorimotor/cognitive function not measured by other tasks. Finally, Tg+ mice had lower survivability than Tg- animals through 9M (85 vs. 96%). In summary, these results demonstrate the presence of gender-related and progressive cognitive deficits in APP(SW) transgenic mice at a relatively early age (i.e., prior to overt, beta-amyloid deposition in the brain), suggesting a pathophysiologic role for elevated levels of 'soluble' beta-amyloid in such impairments.

Sentences and rehearsals increase rated similarity: support for assimilation-in-salience theory.

The present study concerns how organization produces good retention. Exp. 1 indicated that college students rated two words in sentences as more similar than the same two words alone. In Exp. 2 they rated the two words of old presumably rehearsed pairs as more similar than the two words of new pairs. A sentence is a type of organization, and words that are rehearsed together are frequently subjectively organized. Therefore, the two experiments suggest that organized stimuli also assimilate among themselves (and evidence in the literature concurs). Organized stimuli also produce a highly salient (activated) single memorial group (unit) such as the meaning that a simple sentence comes to have according to evidence in the literature. So, the two experiments support the hypothesis that organized stimuli produce good retention, assimilation among themselves, and a highly salient group. Consequently, organized stimuli may also assimilate to the highly salient group and thereby increase in salience, with this increase enabling the good retention. This assimilation-in-salience theory of how organization produces good retention accords with perceptual evidence suggesting that a target increases in salience through its assimilation to a more salient simultaneously present context.

Regular versus randomized sentences, nouns versus prepositions, and assimilation in salience.

The authors' research supports an alternative to the theory that organization improves retention by producing fewer elements for processing. College students' recall of randomized words was better for nouns than for prepositions. Regular sentences improved recall, but this improvement was less for nouns than for prepositions. According to the alternative theory, a part assimilates (increases in similarity) to its high-in-salience organization-produced group, thus increases in salience, and hence is retained better. The high-in-salience group for a regular sentence should be the sentence's meaning. Because the nouns were recalled better, they were more similar in salience to the regular sentences' meanings than were the prepositions. Assimilation should be minimal when parts are very similar. Therefore, the nouns' assimilation in salience should have been less than the prepositions', explaining the nouns' less improvement in recall.

Hemodynamic effects of new intra-aortic balloon counterpulsation timing methods in patients: a multicenter evaluation.

BACKGROUND: To test whether later intra-aortic balloon pump (IABP) deflation approaching or simultaneous with left ventricular ejection would improve hemodynamics and myocardial efficiency with the use of new balloon deflation methods, 4 IABP timing techniques were evaluated in 43 patients. METHODS AND RESULTS: Later balloon deflation produced significantly greater percentage changes in mean aortic pressure (6% vs 1%), systolic pressure time index (-27% vs -20%), diastolic pressure time index (35% vs 19%), and the systolic pressure-time index/diastolic pressure-time index ratio (97% vs 51%), respectively. However, these changes increased peak systolic pressure (-15% vs -11%). Cardiac output and stroke volume indexes were not significantly altered over the 4 settings. CONCLUSIONS: These data suggest that systemic hemodynamics and myocardial efficiency may be improved by later balloon deflation approaching left ventricular ejection in comparison to conventional IABP timing.

Gait characteristics of individuals with multiple sclerosis before and after a 6-month aerobic training program.

Individuals who have multiple sclerosis (MS) typically experience problems with physical activities such as walking, resulting from the combined effects of skeletal muscle weakness, sensory disturbances, spasticity, gait ataxia, and reduction in aerobic capacity. The aim of this study was to determine whether a 6-mo exercise program designed for aerobic conditioning might also affect gait abnormalities in individuals with MS. Subjects included 18 individuals with MS who presented a range of disability. Passive range of motion (PROM) in the lower limbs was measured and gait analyzed before and after exercise conditioning. Three-dimensional kinematics, ground reaction forces (GRF), and electromyographic information were acquired as subjects walked at self-selected velocities. Hip PROM increased following conditioning. Mean walking velocity, cadence, and posterior shear GRF (push-off force) decreased. During walking, maximum ankle dorsiflexion decreased and ankle plantarflexion increased. Total knee flexion/extension range during the walking cycle decreased slightly as did maximum hip extension. Results suggest this 6-mo training program had minimal effect on gait abnormalities.

The Weber fraction versus perceived similarity.

The Weber fraction type of discrimination outcome means that stimuli of high magnitude are difficult to discriminate. Simultaneous and successive discriminations between two long (high magnitude) lines and also between two short (low magnitude) lines were carried out. Over-all performance on the successive discrimination between the two long lines was much poorer than on the three other discriminations. This discrimination also produced the poorest performance on different stimuli relative to same stimuli. The latter result should indicate that the two successive long lines were perceived as most similar. These and additional results support the conclusion that over-all discrimination performance and perceived similarity were consistently associated even though they were not consistently associated with length and time of occurrence (simultaneous versus successive). Nevertheless, the association of discrimination with perceived similarity has received minimal attention in the psychophysics area.

An algorithm for determining gravity line location from posturographic recordings.

In posturographic recordings, the center of pressure (COP) displacement does not accurately reflect migration of the gravity line (GL), the vertical line passing through the body's center of gravity, COG. Since the horizontal ground reaction force, Fx, is proportional to the horizontal acceleration of the COG its second integral does represent the horizontal position of the gravity line (GLP). However, the initial constants of integration, initial velocity and position, are not known. In this note, a technique for estimating these integration constants is suggested: zero-point-to-zero-point integration. This method is based on a postulation that when Fx = 0, the GLP and COP coincide. By integrating Fx from one zero point to another zero point, both the instantaneous GLP and its velocity are determined. A validation of the suggested algorithm was performed using optical methods to determine the GLP during a one legged standing tasks. Cross-correlation values of GLP determined via videography and the suggested algorithm ranged from 0.79 to 0.96. These results suggest that the zero-point-to-zero-point-integration is an acceptable technique for determining GLP from posturographic recordings.

Assimilation and contrast in awareness.

Assimilation and contrast (context-produced increases and decreases in sensed similarity) in awareness may be basic to understanding vision, audition, cognition, and memory. Key considerations follow.

Assimilation in visibility: additional evidence.

The present research tested the theory that a less visible target increases in similarity to a more visible simultaneous context, and that therefore the target increases in visibility. This assimilation-in-visibility theory was tested using context + targets that were either 3-line brackets or 2-line right angles, contexts and targets that were the component lines of these context + targets, with the target always the identical single top line. Experiments with a total of 204 participants indicated that the 3-line context + targets resulted in better context + target versus context discriminations than target versus background discriminations than did the 2-line context + targets. This was so for both over-all errors and misses but not false alarms. It is concluded that only the 3-line context + targets increased the visibility of the 1-line target. Additional analysis indicated that the 2-line contexts of the 3-line context + targets were more visible than all the 1-line stimuli. So, the 1-line target assimilated to a simultaneous more visible 2-line context and thereby increased in visibility, thus improving the context + target versus context discrimination. This support for the assimilation-in-visibility theory is of interest because assimilation and contrast in visibility may play a large role in perception.

Comparison of three-dimensional echocardiographic assessment of volume, mass, and function in children with functionally single left ventricles with two-dimensional echocardiography and magnetic resonance imaging.

Diminished systolic function or inappropriate hypertrophy are considered risk factors for outcome following the Fontan procedure. These parameters are difficult to assess in univentricular hearts that do not conform to the uniform shapes prescribed by conventional 2-dimensional imaging volume algorithms. Three-dimensional echocardiography requires no geometric assumptions and has been validated in both normal and distorted left ventricles. To assess the feasibility and accuracy of this technique in patients with univentricular hearts, we compared 2- and 3-dimensional echocardiographic estimates of ventricular volume, ejection fraction, and mass in patients with functionally single left ventricles with results obtained by magnetic resonance imaging (MRI). Twelve patients with functionally single left ventricles (6 months to 22 years) underwent examination by all 3 modalities. Correlation and agreement with MRI were calculated for volumes, ejection fraction, and mass. Three-dimensional echocardiographic comparison with MRI yielded a bias of 3.4 +/- 5.5 ml and 14.2 +/- 8.3 ml for systolic and diastolic volumes, respectively. Agreement analysis for mass showed a bias of 5.8 +/- 8.4 grams. Two-dimensional echocardiography showed less agreement for both volumes and mass (bias of -2.9 +/- 8.1, 2.9 +/- 10.4 ml and -8.3 +/- 12.0 g for volume and mass, respectively, p >0.05). Ejection fraction by 3-dimensional echocardiography showed significantly closer agreement with MRI (bias of 4.4 +/- 5.3%) than 2-dimensional echocardiography (bias of 8.5 +/- 10.3%, p = 0.04). Thus, 3-dimensional echocardiography provides estimates of ventricular volumes, ejection fraction, and mass that are comparable to MRI in this select group of patients with single ventricles of left ventricular morphology.

Freehand three-dimensional echocardiography for determination of left ventricular volume and mass in patients with abnormal ventricles: comparison with magnetic resonance imaging.

OBJECTIVE: The objective of this study was to validate the freehand three-dimensional echocardiographic method in patients with abnormal ventricular geometry compared with two-dimensional echocardiography using magnetic resonance imaging as a standard. BACKGROUND: Two-dimensional echocardiographic methods for estimating left ventricular volume and mass in clinical use today are limited by inaccuracies and variations caused by use of geometric assumptions and errors in image plane positioning. Freehand three-dimensional echocardiography with operator guidance by a "line of intersection" display eliminates these assumptions and errors. This method of volume and mass computation has been validated as highly accurate and reproducible in healthy subjects. METHODS: Left ventricular end-systolic and end-diastolic volumes and myocardial mass were determined by freehand three-dimensional echocardiography, by conventional two-dimensional echocardiography using the apical biplane summation of discs method (volume) and the truncated ellipsoid method (mass), by M-mode echocardiography using the Penn method (mass), and by magnetic resonance imaging in 30 patients selected only for the presence of an abnormal ventricle. Results were compared by means of linear regression and the Bland-Altman method of analysis. RESULTS: There was excellent correlation, low bias, and low variability between three-dimensional echocardiography and magnetic resonance imaging for end-diastolic volume (r = 0.90, standard error of the estimate = 31.8 ml, bias = -28.4 ml), end-systolic volume (r = 0.93, standard error of the estimate = 24.1 ml, bias = -13.1 ml), and mass (r = 0.90, standard error of the estimate = 27.3 gm, bias = -22.6 ml). Two-dimensional echocardiography was less accurate and more variable as follows: end-diastolic volume (r = 0.70, standard error of the estimate = 39.8 ml, bias = -33.5 ml), end-systolic volume (r = 0.78, standard error of the estimate = 31.2 ml, bias = -26.7 ml), and mass (r = 0.80, standard error of the estimate = 37.3 gm, bias = 28.9 ml). M-mode echocardiography mass determination (Penn method) was least accurate and most variable (r = 0.075, standard error of the estimate = 78.3 gm, bias = 78.3 gm). CONCLUSIONS: Freehand three-dimensional echocardiography is a method of high accuracy and low variability for computing left ventricular volume and mass in clinical patients with abnormal ventricles. It is superior to conventional one- and two-dimensional echocardiography. The improvement achieved is attributed to elimination of geometric assumptions and image plane positioning errors and additional sampling of the ventricle.

Freehand three-dimensional echocardiography for measurement of left ventricular mass: in vivo anatomic validation using explanted human hearts.

OBJECTIVES: We sought to validate freehand three-dimensional echocardiography for measuring left ventricular mass and to compare its accuracy and variability with those of conventional echocardiographic methods. BACKGROUND: Accurate measurement of left ventricular mass is clinically important as a predictor of morbidity and mortality. Freehand three-dimensional echocardiography eliminates geometric assumptions used by conventional methods, minimizes image positioning errors using a line of intersection display and increases sampling of the ventricle. Preliminary studies have shown it to have high accuracy and low variability. METHODS: Twenty-eight patients awaiting heart transplantation were examined by conventional and freehand three-dimensional echocardiography. Left ventricular mass was determined by the M-mode ("Penn-cube") method, the two-dimensional truncated ellipsoid method and three-dimensional surface reconstruction. The ventricles of 20 explanted hearts were obtained, trimmed and weighed. Echocardiographic mass by each method was compared with true mass by linear regression. Accuracy, bias and interobserver variability were calculated. RESULTS: For three-dimensional echocardiography, the correlation coefficient, standard error of the estimate, root mean square percent error (accuracy), bias and interobserver variability were 0.992, 11.9 g, 4.8%, -4.9 g and 11.5%, respectively. For the two-dimensional truncated ellipsoid method they were 0.905, 38.5 g, 15.6%, 15.4 g and 23.3%. For the M-mode ("Penn-cube") method they were 0.721, 96.9 g, 53.0%, 109.2 g and 19.5%. CONCLUSIONS: Freehand three-dimensional echocardiography for measurement of left ventricular mass has high accuracy and low variability and is superior to conventional methods in hearts of abnormal size and geometry.

Group, assimilation, and increase in visibility association without a difference in features.

There is evidence that one group is associated with assimilation among its parts and an increase in visibility (IV) of at least one of its parts: the 1 group-assimilation-IV position. The present research supports this position using physically identical stimuli, hence eliminating differences in features. This was accomplished by comparing the effects of large and small backgrounds on responding to physically identical stimuli that appeared on these backgrounds. Compared to the small background, the large background produced a stronger two-line group according to a closure measure of grouping, more assimilation between two lines according to a same-different measure of perceived similarity, and a greater IV of one of two lines according to context+target versus context relative to target versus background discriminations. The large background was much larger than the two small lines, suggesting that it functioned as an anchor.

Talon cusp with associated adjacent supernumerary tooth.

Talon cusp may occur with other dental anomalies. A case is reported in which talon cusp is associated with a supernumerary tooth, suggesting genetic inheritance as a causative factor.