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Kids who are changing the world
\"Forty-five young people from around the world (including twelve from the U.S. and four from Canada) are doing something every day to make the world a better place. They discovered issues that concerned them and did something about it. With skills ranging from singing, drawing, and painting to fund-raising, public demonstrations, and events, they have fought climate change and pollution, and worked to protect animals and their natural habitats.\"--Amazon.com.
Book
Psychometric assessment of the French European Developmental Coordination Disorder Questionnaire (DCDQ-FE)
The Developmental Coordination Disorder Questionnaire'07 (DCDQ'07) is a parent-report measure to identify children at risk for Developmental Coordination Disorder (DCD). We developed a French version of the DCDQ'07 (DCDQ-FE) that has shown excellent inter-language reliability (intraclass correlation coefficient (ICC) = 0.91) and is culturally relevant for use in European countries. The aims of this study were to examine the internal consistency, test-retest reliability, construct validity of the Developmental Coordination Disorder Questionnaire-French European (DCDQ-FE), as well as establish a cut-off score.
The psychometric properties of the DCDQ-FE were examined with a clinical group of 30 children (mean age: 9.4 years, SD = 2.6) and a control group of 43 children (mean age: 9.1 years, SD = 2.4). Their parents (n = 73) filled out the DCDQ-FE at a first sitting and 70 of them filled it out 38 days later in average for test-retest reliability. The children were assessed using the Movement Assessment Battery for Children-2 (MABC-2) so as to measure the convergent validity of the DCDQ-FE. The cut-off score was determined with an additional sample of 42 children according to scores on the MABC-2 (≥ 16th percentile) (n = 115).
Internal consistency of the DCDQ-FE was excellent (Cronbach's alpha = 0.96) and test-retest reliability was good (ICC = 0.956) with no differences between scores obtained at the two sittings (p > 0.05). Differences in scores between children in the clinical and control groups (Z = -6.58, p < 0.001) provide evidence of construct validity. The correlation obtained between DCDQ-FE and MABC-2 scores (Spearman's rho correlation coefficient = 0.802, p < 0.001) supports convergent validity. Using a cut-off of 56, overall sensitivity and specificity were 85.0% and 81.6% respectively (area under the curve = 0.896). The DCDQ-FE is a reliable and valid questionnaire for detecting children who are at risk for DCD in a European-French population of children aged 5 to 15 years old.
Journal Article
أطلس الطاقة في العالم : هل التنمية العادلة والنظيفة ممكنة ؟
لقد اتخذت معظم الدراسات الحديثة من الجملة منطلقا لها إلى دراسة اللغة، بوصفها أكبر وحدة لغوية تكشف عن النظام التركيبي لأية لغة، فقد تجاوزت هذه الدراسات بحث المفردات، إلى دراسة تركيب الكلام وبنائه، والكشف عن علاقاته ونظامه، من خلال بحث الجملة تركيبا وبناءا. لذا، اختار المؤلف هذا البحث الذي يهدف من خلاله إلى الكشف عن جهود النحاة في هذا الميدان، وذلك بتناول : الجمل التي لا محل لها من الإعراب، التي تعد القسيم الثاني للجملة العربية. وقد سوغ إختياري أيضا ما لقيته هذه الجمل من عزوف كثير من الدراسين عنها، بسبب تسميتها التي قد توحي لطائفة منهم، بقلة جدواها، على الرغم من أصالتها، إذ لا تقبل هذه الجمل التأويل بالمفرد. وقد اختار المؤلف ميدانا تطبيقيا لدراسته، يتفق الجميع على تمثيله للغة العربية بأفضل صورها، وهو القرآن الكريم كتاب العربية الأكبر ومصدر الشريعة الأول، ميدانا لهذه الدراسة، للكشف عن هذا النوع من الجمل فيه، تركيبا وبناءا ودلالة.
BOOK
Reproducible evaluation of classification methods in Alzheimer's disease: Framework and application to MRI and PET data
A large number of papers have introduced novel machine learning and feature extraction methods for automatic classification of Alzheimer's disease (AD). However, while the vast majority of these works use the public dataset ADNI for evaluation, they are difficult to reproduce because different key components of the validation are often not readily available. These components include selected participants and input data, image preprocessing and cross-validation procedures. The performance of the different approaches is also difficult to compare objectively. In particular, it is often difficult to assess which part of the method (e.g. preprocessing, feature extraction or classification algorithms) provides a real improvement, if any. In the present paper, we propose a framework for reproducible and objective classification experiments in AD using three publicly available datasets (ADNI, AIBL and OASIS). The framework comprises: i) automatic conversion of the three datasets into a standard format (BIDS); ii) a modular set of preprocessing pipelines, feature extraction and classification methods, together with an evaluation framework, that provide a baseline for benchmarking the different components. We demonstrate the use of the framework for a large-scale evaluation on 1960 participants using T1 MRI and FDG PET data. In this evaluation, we assess the influence of different modalities, preprocessing, feature types (regional or voxel-based features), classifiers, training set sizes and datasets. Performances were in line with the state-of-the-art. FDG PET outperformed T1 MRI for all classification tasks. No difference in performance was found for the use of different atlases, image smoothing, partial volume correction of FDG PET images, or feature type. Linear SVM and L2-logistic regression resulted in similar performance and both outperformed random forests. The classification performance increased along with the number of subjects used for training. Classifiers trained on ADNI generalized well to AIBL and OASIS. All the code of the framework and the experiments is publicly available: general-purpose tools have been integrated into the Clinica software (www.clinica.run) and the paper-specific code is available at: https://gitlab.icm-institute.org/aramislab/AD-ML.
Journal Article
FHL1 is a major host factor for chikungunya virus infection
Chikungunya virus (CHIKV) is a re-emerging alphavirus that is transmitted to humans by mosquito bites and causes musculoskeletal and joint pain
1
,
2
. Despite intensive investigations, the human cellular factors that are critical for CHIKV infection remain unknown, hampering the understanding of viral pathogenesis and the development of anti-CHIKV therapies. Here we identified the four-and-a-half LIM domain protein 1 (FHL1)
3
as a host factor that is required for CHIKV permissiveness and pathogenesis in humans and mice. Ablation of FHL1 expression results in the inhibition of infection by several CHIKV strains and o’nyong-nyong virus, but not by other alphaviruses and flaviviruses. Conversely, expression of FHL1 promotes CHIKV infection in cells that do not normally express it. FHL1 interacts directly with the hypervariable domain of the nsP3 protein of CHIKV and is essential for the replication of viral RNA. FHL1 is highly expressed in CHIKV-target cells and is particularly abundant in muscles
3
,
4
. Dermal fibroblasts and muscle cells derived from patients with Emery–Dreifuss muscular dystrophy that lack functional FHL1
5
are resistant to CHIKV infection. Furthermore, CHIKV infection is undetectable in Fhl1-knockout mice. Overall, this study shows that FHL1 is a key factor expressed by the host that enables CHIKV infection and identifies the interaction between nsP3 and FHL1 as a promising target for the development of anti-CHIKV therapies.
FHL1 is a key factor expressed by humans and mice that is required for chikungunya virus infection and is therefore a promising target for the development of therapies against chikungunya virus.
Journal Article
Harmonization of radiomic feature distributions: impact on classification of hepatic tissue in CT imaging
Objectives
Following the craze for radiomic features (RF), their lack of reliability raised the question of the generalizability of classification models. Inter-site harmonization of images therefore becomes a central issue. We compared RF harmonization processing designed to detect liver diseases in CT images.
Methods
We retrospectively analyzed 76 multi-center portal CT series of non-diseased (NDL) and diseased liver (DL) patients. In each series, we positioned volumes of interest in spleen and liver, then extracted 9 RF (histogram and texture). We evaluated two RF harmonization approaches. First, in each series, we computed the Z-score of liver measurements based on those computed in the spleen. Second, we evaluated the ComBat method according to each imaging center; parameters were computed in the spleen and applied to the liver. We compared RF distributions and classification performances before/after harmonization. We classified NDL versus spleen and versus DL tissues.
Results
The RF distributions were all different between liver and spleen (
p
< 0.05). The Z-score harmonization outperformed for the detection of liver versus spleen: AUC = 93.1% (
p
< 0.001). For the detection of DL versus NDL, in a case/control setting, we found no differences between the harmonizations: mean AUC = 73.6% (
p
= 0.49). Using the whole datasets, the performances were improved using ComBat (
p
= 0.05) AUC = 82.4% and degraded with Z-score AUC = 67.4% (
p
= 0.008).
Conclusions
Data harmonization requires to first focus on data structuring to not degrade the performances of subsequent classifications. Liver tissue classification after harmonization of spleen-based RF is a promising strategy for improving the detection of DL tissue.
Key Points
•
Variability of acquisition parameter makes radiomics of CT features non-reproducible
.
•
Data harmonization can help circumvent the inter-site variability of acquisition protocols.
•
Inter-site harmonization must be carefully implemented and requires designing consistent data sets.
Journal Article
Cellular and Genomic Features of Muscle Differentiation from Isogenic Fibroblasts and Myoblasts
The ability to recapitulate muscle differentiation in vitro enables the exploration of mechanisms underlying myogenesis and muscle diseases. However, obtaining myoblasts from patients with neuromuscular diseases or from healthy subjects poses ethical and procedural challenges that limit such investigations. An alternative consists in converting skin fibroblasts into myogenic cells by forcing the expression of the myogenic regulator MYOD. Here, we directly compared cellular phenotype, transcriptome, and nuclear lamina-associated domains (LADs) in myo-converted human fibroblasts and myotubes differentiated from myoblasts. We used isogenic cells from a 16-year-old donor, ruling out, for the first time to our knowledge, genetic factors as a source of variations between the two myogenic models. We show that myo-conversion of fibroblasts upregulates genes controlling myogenic pathways leading to multinucleated cells expressing muscle cell markers. However, myotubes are more advanced in myogenesis than myo-converted fibroblasts at the phenotypic and transcriptomic levels. While most LADs are shared between the two cell types, each also displays unique domains of lamin A/C interactions. Furthermore, myotube-specific LADs are more gene-rich and less heterochromatic than shared LADs or LADs unique to myo-converted fibroblasts, and they uniquely sequester developmental genes. Thus, myo-converted fibroblasts and myotubes retain cell type-specific features of radial and functional genome organization. Our results favor a view of myo-converted fibroblasts as a practical model to investigate the phenotypic and genomic properties of muscle cell differentiation in normal and pathological contexts, but also highlight current limitations in using fibroblasts as a source of myogenic cells.
Journal Article
RECIST 1.1 assessments variability: a systematic pictorial review of blinded double reads
Reader variability is intrinsic to radiologic oncology assessments, necessitating measures to enhance consistency and accuracy. RECIST 1.1 criteria play a crucial role in mitigating this variability by standardizing evaluations, aiming to establish an accepted “truth” confirmed by histology or patient survival. Clinical trials utilize Blind Independent Centralized Review (BICR) techniques to manage variability, employing double reads and adjudicators to address inter-observer discordance effectively.It is essential to dissect the root causes of variability in response assessments, with a specific focus on the factors influencing RECIST evaluations. We propose proactive measures for radiologists to address variability sources such as radiologist expertise, image quality, and accessibility of contextual information, which significantly impact interpretation and assessment precision. Adherence to standardization and RECIST guidelines is pivotal in diminishing variability and ensuring uniform results across studies.Variability factors, including lesion selection, new lesion appearance, and confirmation bias, can have profound implications on assessment accuracy and interpretation, underscoring the importance of identifying and addressing these factors. Delving into the causes of variability aids in enhancing the accuracy and consistency of response assessments in oncology, underscoring the role of standardized evaluation protocols and mitigating risk factors that contribute to variability. Access to contextual information is crucial.Critical relevance statementBy understanding the causes of diagnosis variability, we can enhance the accuracy and consistency of response assessments in oncology, ultimately improving patient care and clinical outcomes.Key PointsBaseline lesion selection and detection of new lesions play a major role in the occurrence of discordance.Image interpretation is influenced by contextual information, the lack of which can lead to diagnostic uncertainty.Radiologists must be trained in RECIST criteria to reduce errors and variability.
Journal Article
Childhood cognitive skill trajectories and suicide by mid-adulthood: an investigation of the 1958 British Birth Cohort
Poor cognitive abilities and low intellectual quotient (IQ) are associated with an increased risk of suicide attempts and suicide mortality. However, knowledge of how this association develops across the life-course is limited. Our study aims to establish whether individuals who died by suicide by mid-adulthood are distinguishable by their child-to-adolescence cognitive trajectories.
Participants were from the 1958 British Birth Cohort and were assessed for academic performance at ages 7, 11, and 16 and intelligence at 11 years. Suicides occurring by September 2012 were identified from linked national death certificates. We compared mean mathematics and reading abilities and rate of change across 7-16 years for individuals who died by suicide v. those still alive, with and without adjustment for potential early-life confounding factors. Analyses were based on 14 505 participants.
Fifty-five participants (48 males) had died by suicide by age 54 years. While males who died by suicide did not differ from participants still alive in reading scores at age 7 [effect size (g) = -0.04, p = 0.759], their reading scores had a less steep improvement up to age 16 compared to other participants. Adjustments for early-life confounding factors explained these differences. A similar pattern was observed for mathematics scores. There was no difference between individuals who died by suicide v. participants still alive on intelligence at 11 years.
While no differences in tests of academic performance and IQ were observed, individuals who died by suicide had a less steep improvement in reading abilities over time compared to same-age peers.
Journal Article
RECIST 1.1 and lesion selection: How to deal with ambiguity at baseline?
Response Evaluation Criteria In Solid Tumors (RECIST) is still the predominant criteria base for assessing tumor burden in oncology clinical trials. Despite several improvements that followed its first publication, RECIST continues to allow readers a lot of freedom in their evaluations. Notably in the selection of tumors at baseline. This subjectivity is the source of many suboptimal evaluations. When starting a baseline analysis, radiologists cannot always identify tumor malignancy with any certainty. Also, with RECIST, some findings can be deemed equivocal by radiologists with no confirmatory ground truth to rely on. In the specific case of Blinded Independent Central Review clinical trials with double reads using RECIST, the selection of equivocal tumors can have two major consequences: inter-reader variability and modified sensitivity of the therapeutic response. Apart from the main causes leading to the selection of an equivocal lesion, due to the uncertainty of the radiological characteristics or due to the censoring of on-site evaluations, several other situations can be described more precisely. These latter involve cases where an equivocal is selected as target or non-target lesions, the management of equivocal lymph nodes and the case of few target lesions. In all cases, awareness of the impact of selecting a non-malignant lesion will lead radiologists to make selections in the most rational way. Also, in clinical trials where the primary endpoint differs between phase 2 (response-related) and phase 3 (progression-related) trials, our impact analysis will help them to devise strategies for the management of equivocal lesions.
Journal Article