Dysgraphia Differs Between Children With Developmental Coordination Disorder and/or Reading Disorder.

Handwriting deficits, or dysgraphia, are present in several neurodevelopmental disorders. To investigate whether dysgraphia differs according to the associated disorder, we performed a detailed analysis of handwriting in children with developmental coordination disorders (DCD), reading disorder (RD), or comorbid RD and DCD. Handwriting deficits were investigated at the product (quality of the trace) and the process (movement that generates the trace) levels. Nineteen children with singular RD (among which eight with dysgraphia), 13 children with singular DCD (among which seven with dysgraphia), 16 children with comorbid RD+DCD (among which 11 with dysgraphia), and 20 typically developing children, age 7 to 12, performed the BHK (Brave Handwriting Kinder) test, a standardized assessment of handwriting, on a graphic tablet. Developmental coordination disorders primarily affected handwriting quality, while RD affected slowness and, to a lesser extent, quality. Children with RD, solely or comorbid with DCD, wasted time by lifting and stopping the pen when writing. The comorbidity added to but did not worsen, handwriting difficulties. These results reflect distinct motor impairments and/or strategies in children with DCD or RD. We identified subtypes of dysgraphia and advocated for a fine-grained analysis of the writing process and the assessment of motor and reading skills when studying dysgraphia.

Tools and Methods for Diagnosing Developmental Dysgraphia in the Digital Age: A State of the Art.

Handwriting is a complex perceptual motor task that requires years of training and practice before complete mastery. Its acquisition is crucial, since handwriting is the basis, together with reading, of the acquisition of higher-level skills such as spelling, grammar, syntax, and text composition. Despite the correct learning and practice of handwriting, some children never master this skill to a sufficient level. These handwriting deficits, referred to as developmental dysgraphia, can seriously impact the acquisition of other skills and thus the academic success of the child if they are not diagnosed and handled early. In this review, we present a non-exhaustive listing of the tools that are the most reported in the literature for the analysis of handwriting and the diagnosis of dysgraphia. A variety of tools focusing on either the final handwriting product or the handwriting process are described here. On one hand, paper-and-pen tools are widely used throughout the world to assess handwriting quality and/or speed, but no universal gold-standard diagnostic test exists. On the other hand, several very promising computerized tools for the diagnosis of dysgraphia have been developed in the last decade, but some improvements are required before they can be available to clinicians. Based on these observations, we will discuss the pros and cons of the existing tools and the perspectives related to the development of a universal, standardized test of dysgraphia combining both paper-and-pen and computerized approaches and including different graphomotor and writing tasks.

Towards a Holistic Model Explaining Hearing Protection Device Use among Workers.

Offering hearing protection devices (HPDs) to workers exposed to hazardous noise is a noise control strategy often used to prevent noise-induced hearing loss (NIHL). However, HPDs are used incorrectly and inconsistently, which explains their limited efficiency. Numerous models based on social cognition theories identify the significant factors associated with inconsistent HPD use and aim to improve HPD training programs and to increase HPD use. However, these models do not detail (dis)comfort aspects originating from complex interactions between characteristics of the triad "environment/person/HPD" while these aspects are known to largely influence HPD (mis)use. This paper proposes a holistic model explaining HPD (mis)use, based on the integration of a comfort model adapted to HPDs into an existing behavioral model already developed for HPDs. The model also takes into account the temporal dimension, which makes it possible to capture the scope of change in HPD-related health behaviors. This holistic description of HPD use could be used as a tool for stakeholders involved in HPD use to effectively prevent NIHL among workers.

A critical review of the literature on comfort of hearing protection devices: analysis of the comfort measurement variability.

Objective. This article proposes a comprehensive literature review of past works addressing hearing protection device (HPD) comfort with the aim of identifying the main sources of variability in comfort evaluation. Methods. A literature review of study samples was performed: documents were hand searched and Internet searched using PubMed, Web of Science, Google Scholar, ProQuest Dissertations and Theses Professional, Scopus or Google search engines. While comfort constructs and measurement methods are reviewed for both earplugs and earmuff HPD types, results and analyses are provided for earplugs only. Results. The literature shows that the multiple sources of the perceived comfort measurement variability are related to the complexity of the concept of comfort and to the various physical and psychosocial characteristics of the triad 'environment/person/earplug', which differ from one study to the other. Conclusions. Considering the current state of knowledge and in order to decrease comfort measurements variability, it is advised to: (a) use a multidimensional construct of comfort and derive a comfort index for each comfort dimension;, (b) use exhaustive and valid questionnaires; (c) quantify as many triad characteristics as possible and use them as independent or control variables; (d) assess the quality of the earplug fitting and the attenuation efficiency.

Analysis of Graphomotor Tests with Machine Learning Algorithms for an Early and Universal Pre-Diagnosis of Dysgraphia.

Five to ten percent of school-aged children display dysgraphia, a neuro-motor disorder that causes difficulties in handwriting, which becomes a handicap in the daily life of these children. Yet, the diagnosis of dysgraphia remains tedious, subjective and dependent to the language besides stepping in late in the schooling. We propose a pre-diagnosis tool for dysgraphia using drawings called graphomotor tests. These tests are recorded using graphical tablets. We evaluate several machine-learning models and compare them to build this tool. A database comprising 305 children from the region of Grenoble, including 43 children with dysgraphia, has been established and diagnosed by specialists using the BHK test, which is the gold standard for the diagnosis of dysgraphia in France. We performed tests of classification by extracting, correcting and selecting features from the raw data collected with the tablets and achieved a maximum accuracy of 73% with cross-validation for three models. These promising results highlight the relevance of graphomotor tests to diagnose dysgraphia earlier and more broadly.

Acquisition of handwriting in children with and without dysgraphia: A computational approach.

Handwriting is a complex skill to acquire and it requires years of training to be mastered. Children presenting dysgraphia exhibit difficulties automatizing their handwriting. This can bring anxiety and can negatively impact education. 280 children were recruited in schools and specialized clinics to perform the Concise Evaluation Scale for Children's Handwriting (BHK) on digital tablets. Within this dataset, we identified children with dysgraphia. Twelve digital features describing handwriting through different aspects (static, kinematic, pressure and tilt) were extracted and used to create linear models to investigate handwriting acquisition throughout education. K-means clustering was performed to define a new classification of dysgraphia. Linear models show that three features only (two kinematic and one static) showed a significant association to predict change of handwriting quality in control children. Most kinematic and statics features interacted with age. Results suggest that children with dysgraphia do not simply differ from ones without dysgraphia by quantitative differences on the BHK scale but present a different development in terms of static, kinematic, pressure and tilt features. The K-means clustering yielded 3 clusters (Ci). Children in C1 presented mild dysgraphia usually not detected in schools whereas children in C2 and C3 exhibited severe dysgraphia. Notably, C2 contained individuals displaying abnormalities in term of kinematics and pressure whilst C3 regrouped children showing mainly tilt problems. The current results open new opportunities for automatic detection of children with dysgraphia in classroom. We also believe that the training of pressure and tilt may open new therapeutic opportunities through serious games.

A critical review of the literature on comfort of hearing protection devices: definition of comfort and identification of its main attributes for earplug types.

Objective: This article presents a comprehensive literature review of past works addressing Hearing Protection Devices (HPD) comfort and to put them into perspective regarding a proposed holistic multidimensional construct of HPD comfort.Design: Literature review.Study samples: Documents were hand searched and Internet searched using "PubMed", "Web of Science", "Google Scholar", "ProQuest Dissertations and Theses Professional", "Scopus" or "Google" search engines. While comfort constructs and measurement methods are reviewed for both earplugs and earmuff types, results and analyses are provided for the earplug type only.Results: This article proposed a multidimensional construct of HPD comfort based on four dimensions: physical, functional, acoustical and psychological. Seen through the prism of the proposed holistic construct of HPD comfort, the main comfort attributes of earplugs have been identified for each comfort dimension.Conclusions: The observed lack of consensus on the definition of HPD comfort in the scientific community makes it difficult to prioritise the importance of comfort attributes yet necessary for future design of comfortable earplugs.

Automated human-level diagnosis of dysgraphia using a consumer tablet.

The academic and behavioral progress of children is associated with the timely development of reading and writing skills. Dysgraphia, characterized as a handwriting learning disability, is usually associated with dyslexia, developmental coordination disorder (dyspraxia), or attention deficit disorder, which are all neuro-developmental disorders. Dysgraphia can seriously impair children in their everyday life and require therapeutic care. Early detection of handwriting difficulties is, therefore, of great importance in pediatrics. Since the beginning of the 20th century, numerous handwriting scales have been developed to assess the quality of handwriting. However, these tests usually involve an expert investigating visually sentences written by a subject on paper, and, therefore, they are subjective, expensive, and scale poorly. Moreover, they ignore potentially important characteristics of motor control such as writing dynamics, pen pressure, or pen tilt. However, with the increasing availability of digital tablets, features to measure these ignored characteristics are now potentially available at scale and very low cost. In this work, we developed a diagnostic tool requiring only a commodity tablet. To this end, we modeled data of 298 children, including 56 with dysgraphia. Children performed the BHK test on a digital tablet covered with a sheet of paper. We extracted 53 handwriting features describing various aspects of handwriting, and used the Random Forest classifier to diagnose dysgraphia. Our method achieved 96.6% sensibility and 99.2% specificity. Given the intra-rater and inter-rater levels of agreement in the BHK test, our technique has comparable accuracy for experts and can be deployed directly as a diagnostics tool.

Analysis of cursive letters, syllables, and words handwriting in a French second-grade child with Developmental Coordination Disorder and comparison with typically developing children.

Poor handwriting is a core deficit in Developmental Coordination Disorder (DCD). In a previous study, we compared the evolution of cursive letters handwriting in a girl with DCD throughout her second-grade year with that of typically developing (TD) children. We found that her handwriting evolved much less than that of TD children and remained similar to that of pre-schoolers at all stages, suggesting that her handwriting skills have reached a steady state level. We present here a continuation of this work, in which we focused on the velocity aspects of handwriting in another French child with DCD. Indeed, different velocity patterns have been observed in Chinese and English children with DCD. In the French cursive style of writing, consecutive letters are joined, a major difference with the English script style of writing. We thus analyzed the handwriting of a second-grade French girl with DCD, not only for isolated letters but also for syllables and words, in comparison to that of TD first-graders (6-7 years old; N = 85) and second-graders (7-8 years old; N = 88). Each written track was digitized, and nine kinematic parameters were measured to evaluate writing fluency. Results showed that the productions of the child with DCD were more similar to those of first-graders than to those of second-graders. In line with our previous study, the most discriminative parameters between the child with DCD and TD children were size and mean speed. Moreover, her handwriting was less fluent than that of TD children. In contrast to previous observations, we observed a higher writing velocity of the child with DCD when compared to TD children, whatever the complexity of the item, and no significant difference with TD children in the pausing time during writing. These differences may reflect linguistic specificities. For syllables and words, each letter was treated separately as a single unit, thus reflecting a problem in anticipation and automation.

Heat shock factor 1 binds to and transcribes satellite II and III sequences at several pericentromeric regions in heat-shocked cells.

Cells respond to stress by activating the synthesis of heat shock proteins (HSPs) which protect the cells against the deleterious effects of stress. This mechanism is controlled by the heat shock factor 1 (HSF1). In parallel to HSP gene transcription, in human cells, HSF1 also binds to and transcribes satellite III repeated sequences present in numerous copies in the 9q12 pericentromeric region of chromosome 9. These HSF1 accumulation sites are termed nuclear stress bodies (nSBs). In tumor cells, however, the number of nSBs is higher than the number of 9q12 copies, suggesting the existence of other HSF1 targets. In this paper, we were interested in characterizing these other HSF1 binding sites. We show that HSF1 indeed binds to the pericentromeric region of 14 chromosomes, thereby directing the formation of 'secondary nSBs'. The appearance of secondary nSBs depends on the number of satellite sequences present in the target locus, and on the cellular amount of HSF1 protein. Moreover, secondary nSBs also correspond to transcription sites, thus demonstrating that heat shock induces a genome-wide transcription of satellite sequences. Finally, by analyzing published transcriptomic data, we show that the derepression of these large heterochromatic blocks does not significantly affect the transcription of neighboring genes.

Heat-shock factor 1 controls genome-wide acetylation in heat-shocked cells.

A major regulatory function has been evidenced here for HSF1, the key transcription factor of the heat-shock response, in a large-scale remodeling of the cell epigenome. Indeed, upon heat shock, HSF1, in addition to its well-known transactivating activities, mediates a genome-wide and massive histone deacetylation. Investigating the underlying mechanisms, we show that HSF1 specifically associates with and uses HDAC1 and HDAC2 to trigger this heat-shock-dependent histone deacetylation. This work therefore identifies HSF1 as a master regulator of global chromatin acetylation and reveals a cross-talk between HSF1 and histone deacetylases in the general control of genome organization in response to heat shock.

Heterotrimerization of heat-shock factors 1 and 2 provides a transcriptional switch in response to distinct stimuli.

Organisms respond to circumstances threatening the cellular protein homeostasis by activation of heat-shock transcription factors (HSFs), which play important roles in stress resistance, development, and longevity. Of the four HSFs in vertebrates (HSF1-4), HSF1 is activated by stress, whereas HSF2 lacks intrinsic stress responsiveness. The mechanism by which HSF2 is recruited to stress-inducible promoters and how HSF2 is activated is not known. However, changes in the HSF2 expression occur, coinciding with the functions of HSF2 in development. Here, we demonstrate that HSF1 and HSF2 form heterotrimers when bound to satellite III DNA in nuclear stress bodies, subnuclear structures in which HSF1 induces transcription. By depleting HSF2, we show that HSF1-HSF2 heterotrimerization is a mechanism regulating transcription. Upon stress, HSF2 DNA binding is HSF1 dependent. Intriguingly, when the elevated expression of HSF2 during development is mimicked, HSF2 binds to DNA and becomes transcriptionally competent. HSF2 activation leads to activation of also HSF1, revealing a functional interdependency that is mediated through the conserved trimerization domains of these factors. We propose that heterotrimerization of HSF1 and HSF2 integrates transcriptional activation in response to distinct stress and developmental stimuli.

Human sat III and Drosophila hsr omega transcripts: a common paradigm for regulation of nuclear RNA processing in stressed cells.

Exposure of cells to stressful conditions elicits a highly conserved defense mechanism termed the heat shock response, resulting in the production of specialized proteins which protect the cells against the deleterious effects of stress. The heat shock response involves not only a widespread inhibition of the ongoing transcription and activation of heat shock genes, but also important changes in post-transcriptional processing. In particular, a blockade in splicing and other post-transcriptional processing has been described following stress in different organisms, together with an altered spatial distribution of the proteins involved in these activities. However, the specific mechanisms that regulate these activities under conditions of stress are little understood. Non-coding RNA molecules are increasingly known to be involved in the regulation of various activities in the cell, ranging from chromatin structure to splicing and RNA degradation. In this review, we consider two non-coding RNAs, the hsr(omega) transcripts in Drosophila and the sat III transcripts in human cells, that seem to be involved in the dynamics of RNA-processing factors in normal and/or stressed cells, and thus provide new paradigms for understanding transcriptional and post-transcriptional regulations in normal and stressed cells.

A key role for stress-induced satellite III transcripts in the relocalization of splicing factors into nuclear stress granules.

Exposure of cells to stressful conditions results in the rapid synthesis of a subset of specialized proteins termed heat shock proteins (HSPs) which function in protecting the cell against damage. The stress-induced activation of hsp genes is controlled by the heat shock transcription factor 1 (HSF1). At the cellular level, one of the most striking effects of stress is the rapid and reversible redistribution of HSF1 into a few nuclear structures termed nuclear stress granules which form primarily on the 9q12 locus in humans. Within these structures, HSF1 binds to satellite III repeated elements and drives the RNA polymerase II-dependent transcription of these sequences into stable RNAs which remain associated with the 9q12 locus for a certain time after synthesis. Other proteins, in particular splicing factors, were also shown to relocalize to the granules upon stress. Here, we investigated the role of stress-induced satellite III transcripts in the relocalization of splicing factors to the granules. We show that the recruitment of the two serine/arginine-rich (SR) proteins SF2/ASF and SRp30c requires the presence of stress-induced satellite III transcripts. In agreement with these findings, we identified the second RNA-recognition motif (RRM2) of hSF2/ASF as the motif required for the targeting to the granules, and we showed by immunoprecipitation that the endogenous hSF2/ASF protein is present in a complex with satellite III transcripts in stressed cells in vivo. Interestingly, satellite III transcripts also immunoprecipitate together with small nuclear ribonucleoproteins (snRNPs) in vivo whereas the intronless hsp70 transcripts do not, supporting the proposal that these transcripts are subject to splicing. Altogether, these data highlight the central role for satellite III transcripts in the targeting and/or retention of splicing factors into the granules upon stress.

Stress-induced transcription of satellite III repeats.

Exposure of mammalian cells to stress induces the activation of heat shock transcription factor 1 (HSF1) and the subsequent transcription of heat shock genes. Activation of the heat shock response also correlates with a rapid relocalization of HSF1 within a few nuclear structures termed nuclear stress granules. These stress-induced structures, which form primarily on the 9q12 region in humans through direct binding of HSF1 to satellite III repeats, do not colocalize with transcription sites of known hsp genes. In this paper, we show that nuclear stress granules correspond to RNA polymerase II transcription factories where satellite III repeats are transcribed into large and stable RNAs that remain associated with the 9q12 region, even throughout mitosis. This work not only reveals the existence of a new major heat-induced transcript in human cells that may play a role in chromatin structure, but also provides evidence for a transcriptional activity within a locus considered so far as heterochromatic and silent.

In vivo binding of active heat shock transcription factor 1 to human chromosome 9 heterochromatin during stress.

Activation of the mammalian heat shock transcription factor (HSF)1 by stress is a multistep process resulting in the transcription of heat shock genes. Coincident with these events is the rapid and reversible redistribution of HSF1 to discrete nuclear structures termed HSF1 granules, whose function is still unknown. Key features are that the number of granules correlates with cell ploidy, suggesting the existence of a chromosomal target. Here we show that in humans, HSF1 granules localize to the 9q11-q12 heterochromatic region. Within this locus, HSF1 binds through direct DNA-protein interaction with a nucleosome-containing subclass of satellite III repeats. HSF1 granule formation only requires the DNA binding competence and the trimerization of the factor. This is the first example of a transcriptional activator that accumulates transiently and reversibly on a chromosome-specific heterochromatic locus.