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Hole U1395B, drilled southeast of Montserrat during Integrated Ocean Drilling Program Expedition 340, provides a long (>1 Ma) and detailed record of eruptive and mass-wasting events (>130 discrete events). This record can be used to explore the temporal evolution in volcanic activity and landslides at an arc volcano. Analysis of tephra fall and volcaniclastic turbidite deposits in the drill cores reveals three heightened periods of volcanic activity on the island of Montserrat (∼930 to ∼900 ka, ∼810 to ∼760 ka, and ∼190 to ∼120 ka) that coincide with periods of increased volcano instability and mass-wasting. The youngest of these periods marks the peak in activity at the Soufrière Hills volcano. The largest flank collapse of this volcano (∼130 ka) occurred toward the end of this period, and two younger landslides also occurred during a period of relatively elevated volcanism. These three landslides represent the only large (>0.3 km3) flank collapses of the Soufrière Hills edifice, and their timing also coincides with periods of rapid sea level rise (>5 m/ka). Available age data from other island arc volcanoes suggest a general correlation between the timing of large landslides and periods of rapid sea level rise, but this is not observed for volcanoes in intraplate ocean settings. We thus infer that rapid sea level rise may modulate the timing of collapse at island arc volcanoes, but not in larger ocean-island settings.

©2015. The Authors. Volcanic edifice collapses generate some of Earth's largest landslides. How such unloading affects the magma storage systems is important for both hazard assessment and for determining long-term controls on volcano growth and decay. Here we present a detailed stratigraphic and petrological analyses of volcanic landslide and eruption deposits offshore Montserrat, in a subduction zone setting, sampled during Integrated Ocean Drilling Program Expedition 340. A large (6-10km3) collapse of the Soufrière Hills Volcano at ~130ka was followed by explosive basaltic volcanism and the formation of a new basaltic volcanic center, the South Soufrière Hills, estimated to have initiated

IODP Expedition 340 successfully drilled a series of sites offshore Montserrat, Martinique and Dominica in the Lesser Antilles from March to April 2012. These are among the few drill sites gathered around volcanic islands, and the first scientific drilling of large and likely tsunamigenic volcanic island-arc landslide deposits. These cores provide evidence and tests of previous hypotheses for the composition and origin of those deposits. Sites U1394, U1399, and U1400 that penetrated landslide deposits recovered exclusively seafloor sediment, comprising mainly turbidites and hemipelagic deposits, and lacked debris avalanche deposits. This supports the concepts that i/ volcanic debris avalanches tend to stop at the slope break, and ii/ widespread and voluminous failures of preexisting low-gradient seafloor sediment can be triggered by initial emplacement of material from the volcano. Offshore Martinique (U1399 and 1400), the landslide deposits comprised blocks of parallel strata that were tilted or microfaulted, sometimes separated by intervals of homogenized sediment (intense shearing), while Site U1394 offshore Montserrat penetrated a flat-lying block of intact strata. The most likely mechanism for generating these large-scale seafloor sediment failures appears to be propagation of a decollement from proximal areas loaded and incised by a volcanic debris avalanche. These results have implications for the magnitude of tsunami generation. Under some conditions, volcanic island landslide deposits composed of mainly seafloor sediment will tend to form smaller magnitude tsunamis than equivalent volumes of subaerial block-rich mass flows rapidly entering water. Expedition 340 also successfully drilled sites to access the undisturbed record of eruption fallout layers intercalated with marine sediment which provide an outstanding high-resolution data set to analyze eruption and landslides cycles, improve understanding of magmatic evolution as well as offshore sedimentation processes.

Abstract: Studying the older volcanic centers on Montserrat, Centre Hills and Silver Hills, may reveal how volcanic activity can change over long time periods (≥1 Myr), and whether the recent activity at the Soufrière Hills is typical of volcanism throughout Montserrat's history. Here we present the first detailed mapping of the Silver Hills, the oldest and arguably least studied volcanic center on Montserrat. Volcanism at the Silver Hills was dominated by episodic andesite lava dome growth and collapse, produced Vulcanian style eruptions, and experienced periodic sector collapse events, similar to the style of volcanic activity that has been documented for the Centre Hills and Soufrière Hills. We also present an updated geochronology of volcanism on Montserrat, by revising existing ages and obtaining new 40Ar/39Ar dates and paleomagnetic ages from marine tephra layers. We show that the centers of the Silver, Centre, and Soufrière Hills were active during at least ∼2.17–1.03 Ma, ∼1.14–0.38 Ma, and ∼0.45 Ma to present, respectively. Combined with timings of volcanism on Basse‐Terre, Guadeloupe, these ages suggest that ∼0.5–1 Ma is a common lifespan for volcanic centers in the Lesser Antilles. These new dates identify a previously unrecognized overlap in activity between the different volcanic centers, which appears to be a common phenomenon in island arcs. We also identify an older stage of Soufrière Hills activity ∼450–290 ka characterized by the eruption of hornblende‐orthopyroxene‐phyric lavas, demonstrating that the petrology of the Soufrière Hills eruptive products has changed at least twice throughout the volcano's development. [ABSTRACT FROM AUTHOR]

Factors influencing quality of life for persons with Asperger syndrome are not yet understood. Men, ages 18 to 21, completed the World Health Organization Quality Of Life measure, the Perceived Support Network Inventory, and a semi-structured interview. Asperger syndrome affects quality of life beyond the obvious social impact. The 12 men with Asperger syndrome reported a significantly lower social and physical quality of life than did the 13 men in the control group. Education, living arrangements, and number of friends were remarkably similar between groups. Those with Asperger syndrome had less positive employment experiences and showed more preference for solitary activities. Interventions need to be based on a holistic model. [ABSTRACT FROM AUTHOR]

Impaired muscle parameters may further compromise the already compromised skeleton in individuals with OI. This cross-sectional study aimed to compare muscle function and body composition in adults with various OI types and healthy controls. Sixty-eight adults with OI (mean age 42.2 yr; 27 men) and 68 healthy age- and sex-matched controls were recruited. Maximal isometric muscle force was assessed by handheld dynamometry (hand grip, hip flexors, shoulder abductors, and ankle dorsiflexors), muscle endurance by posture maintenance tests (shoulder abduction, hip flexion, and wall sit), and functional lower limb strength by 30-s chair rise test. In a sub cohort, dynamic muscle function (peak power and force) was assessed by a ground reaction force plate, and lean and fat mass, muscle and fat cross-sectional area (CSA), and muscle density by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Multiple linear regression models were fitted with group (OI type I, III, IV/V, or controls), country, sex, and age in the fixed effects part. Overall, adults with various types of OI had lower isometric, endurance, and functional muscle strength (mean difference [MD] = OI type I: 19-43%, OI type IV/V: 25-68%, OI type III: 20-72%) compared to controls. Furthermore, adults with OI type I had lower dynamic muscle function (peak force [MD = 25-29%] and power [MD = 18-60%]), lean mass (MD = 10-17%), muscle CSA (MD = 9-21%), and muscle density (MD = 2-3%) but higher adiposity indices (MD = 24-42%) compared to controls. Functional lower limb strength and maximal muscle force were significantly different between OI types, whereas muscle endurance was not. To conclude, adults with OI present with markedly impaired muscle function which may partially be explained by their altered body composition. Our findings emphasize the need for proper assessment of various muscle parameters and (research into) appropriate and safe muscle strengthening approaches in this population., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To compare bone parameters between individuals with hypermobile Ehlers-Danlos syndrome (hEDS) and generalized joint hypermobility spectrum disorder (G-HSD), both diagnosed according to the most recent diagnostic criteria, and with controls., Methods: Twenty female adults with hEDS (mean age 43.8 years), 20 with G-HSD (mean age 41.8 years), and 37 healthy controls (mean age 40.8 years) participated. Body composition and bone parameters at whole body and lumbar spine were assessed by dual-energy X-ray absorptiometry. Peripheral quantitative computed tomography at the lower leg evaluated body composition (66 % site), and trabecular (4 % site) and cortical (66 % site) bone parameters at the tibia., Results: No significantly different body composition and bone parameters were observed between hEDS and G-HSD. Compared to controls, individuals with hEDS and G-HSD had lower muscle mass (p = 0.004 and p < 0.001, respectively) and cross-sectional area (p = 0.025 and p < 0.001, respectively), cortical bone mineral content (BMC; p = 0.024 and p = 0.027, respectively) and area (p = 0.019 and p = 0.010, respectively). Additionally, individuals with hEDS had lower muscle density (p = 0.009), trabecular BMC (p = 0.027) and bone mineral density (p = 0.022), and individuals with G-HSD lower stress-strain index (p = 0.019), and periosteal and endosteal circumference (p = 0.002 and 0.025, respectively), compared to controls., Conclusion: Results indicated lower cortical bone mineral content and smaller cortices in hEDS and G-HSD compared to controls. Individuals with hEDS and G-HSD had no different bone parameters, suggesting that these impairments might not be reflected by the different diagnostic classification. Therefore, we recommend regular physical activity, and training to reduce the risk of falling in both hEDS or G-HSD., Competing Interests: Declaration of competing interest There are no financial interests that any of the authors (Coussens M, Banica T, Lapauw B, De Wandele I, Rombaut L, Malfait F, Calders P) may have, which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous heritable connective tissue disorder mainly characterized by bone fragility and increased fracture risk. This study investigated bone parameters in adults with OI type I and their relationship with physical activity and muscle function parameters in comparison with controls. A total of 27 (15 women, 12 men) adults with OI type I and 27 healthy age- and sex-matched controls, with mean age 45 years (range 18-72 years), were included. Peripheral quantitative computed tomography was performed at the lower leg and forearm to assess muscle density, muscle and fat cross-sectional area (CSA) (66% site), and trabecular (4% site) and cortical bone parameters (66% site) at radius and tibia. Physical activity (step count and moderate-to-vigorous physical activity [MVPA]) was assessed by accelerometry, muscle function parameters by Leonardo mechanography (single two-legged jump - peak power), and hand grip dynamometry (maximal hand grip strength). Overall, the OI type I group had significantly lower muscle CSA at the lower leg and forearm, lower trabecular and cortical bone mineral content, lower polar stress-strain index (SSIp), and smaller cortices but higher cortical bone mineral density and lower step count and MVPA in comparison with controls. Maximal hand grip strength was positively associated with SSIp at radius (p = 0.012) in the control group but not in the OI type I group (p = 0.338) (difference in associations: p = 0.012). No other significantly different associations between bone and muscle function parameters or physical activity (step count or MVPA) were found in the OI type I versus control group. We conclude that adults with OI type I have smaller bones, lower trabecular bone mass, lower estimates of bone strength, and higher cortical density in comparison with controls and that there are some indications of a disturbed biomechanical muscle-bone relationship in adults with OI type I. © 2022 American Society for Bone and Mineral Research (ASBMR)., (© 2022 American Society for Bone and Mineral Research (ASBMR).)

Participation has become an important measure of outcome in child rehabilitation as young children with developmental disabilities are increasingly at risk of decreased participation. Therefore, this study garnered information on clinicians' perspectives regarding perceived facilitators and barriers when rendering participation-based interventions using a qualitative research design. Semi-structured interviews of clinicians (Ns = 12, 25-57 years) were conducted and evaluated via an inductive thematic analysis. Results denote that current mechanisms of providing participation-based interventions resembled traditionally focused interventions; thus, resulting in a knowledge-to-practice gap. Clinicians desired more opportunities to communicate with caregivers and to be able to influence the children' s natural environments. They also identified shortness of time, resources, and rigid health care regulations as barriers hampering the efficacy of participation-based services., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To evaluate differences in physical impairment, muscle strength, muscle mass and muscle density between patients with hypermobile Ehlers Danlos Syndrome (hEDS), hypermobile spectrum disorder (HSD), and healthy controls., Methods: Female adults with hEDS (n=20) and HSD (n=23), diagnosed to the most recent criteria, and age-matched healthy controls (n=28) completed the Arthritis Impact Measurement Scale (physical functioning) and performed maximal muscle strength and strength endurance tests of lower and upper limbs (hand grip, posture maintenance, 30 seconds chair rise and isokinetic tests). Muscle mass and density were evaluated by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography., Results: No differences in physical functioning and muscle strength were found between adults with hEDS and HSD. Furthermore, no differences in muscle mass and density were observed between the three groups. Nevertheless, when both patient groups were compared to controls, physical functioning, maximal muscle strength and muscle strength endurance were significantly lower (all p<0.001), except for the hand flexors., Conclusion: Physical functioning, muscle strength, density and mass did not significantly differ between individuals with hEDS and HSD. Compared to controls, physical functioning and muscle strength (maximal and endurance) were significantly lower. Consequently, (functional) strength training in individuals with hEDS and HSD is necessary., Competing Interests: The authors have no conflict of interest.

Objective: Reduced maximal muscle strength and strength endurance have been found in patients with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder (hEDS/HSD) and are recognized as common associated features of the disorder. However, the extent to which these parameters change over time is currently not documented. Therefore, the purpose of this 8-year follow-up study was to investigate this evolution., Methods: Thirty female patients (mean age 41 years) with hEDS/HSD and 17 controls participated at baseline and 8 years later. Maximal muscle strength and strength endurance tests of the knee flexors and extensors, and 2 lower-extremity posture maintenance tests were performed to evaluate static strength endurance. In addition, muscle mass and density were evaluated by dual-energy x-ray absorptiometry and peripheral quantitative computed tomography., Results: Maximal muscle strength and strength endurance were significantly lower at both baseline and follow-up in the hEDS/HSD group compared to the control group (P ≤ 0.007). Maximal muscle strength of the knee flexors (decreased in the control group: pɳ 2 = 0.139), strength endurance of the knee extensors (decreased in the hEDS/HSD group and increased in the control group: pɳ 2 = 0.244), and muscle density (decreased in the hEDS/HSD group: pɳ 2 = 0.263) showed a significantly different evolution over 8 years. No other significant differences in evolution were found., Conclusion: Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients., (© 2020, American College of Rheumatology.)

Objectives: Participation refers to a person's involvement in activities and roles that provide interaction with others as well as engagement in family and community activities. Young children with developmental disabilities (DD) such as attention deficit hyperactive disorder, autism spectrum disorder and developmental coordination disorder are limited in their participation compared with their typically developing peers. This study aimed to obtain information regarding parental needs and strategies used to enable their child's participation., Design: A thematic inductive approach with in-depth interviews was used to explore parental experiences. Eleven women and two men, between 30 and 40 years of age, who had a child (4-9 years old) with a DD diagnosis based on Diagnostic and Statistical Manual of Mental Disorders criteria, participated in semistructured interviews., Results: Two central themes emerged: parental needs and parental strategies used to enable their child's participation. Parental needs were the following: increasing awareness, ameliorating parental burden, providing tailored interventions and supporting parents in finding suitable leisure activities. Parental strategies aimed at increasing their child's resiliency, attaining maximal fit between activity requirements and child capacity, and creating inclusive opportunities and awareness., Conclusions: Understanding what families' needs are and how families use and integrate strategies within the context of their daily lives provides practitioners with insights needed to support families' resiliency in promoting their children's participation. The results have implications for professionals as this information can be used to inform, refine, or tailor participation-based and family-centred services., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: "Ehlers - Danlos syndrome" (EDS) is a heritable connective disorder influencing multiple aspects of daily life. Most studies have focused on describing the physical symptoms and level of disability, but little knowledge exists about the psychosocial effects of the pathology. Participation in employment is an aspect that strongly influences quality of life of patients with chronic pathologies. This study, therefore, aimed to explore the lived experiences in employment participation of patients diagnosed with "hypermobile EDS"., Methods: An inductive thematic analysis, using semi-structured interviews was used. Nine patients, purposively selected by a continuum sampling strategy, were included. Interviews were audio-recorded and transcribed verbatim., Results: Data analysis resulted in three main themes: (1) elements assisting participation in employment, (2) limitations in employment participation, and (3) unemployment due to the "hypermobile EDS". On the one hand, the results show that related health complaints can impede employment participation to an important extent. On the other hand, patients also report several aspects of work that can affect their well-being in a positive way., Conclusion: There are specific reasons for a person with "hypermobile EDS" to participate in employment. These reasons are different for each person and may even vary in time.Implications for rehabilitation"Hypermobile EDS" greatly impacts activities and participation in daily life. "Living with limitations" is the central theme in the lives of "Hypermobile EDS" patients.Various aspects influence work participation in people with "Hypermobile EDS", such as work pressure, tasks, and transport to work.Work has positive effects in the lives of people with "Hypermobile EDS."Work can create difficulties when the job requirements and tasks do not match the functional abilities of a person with "Hypermobile EDS."

Background: Skeletal dysplasia are genetic disorders of cartilage and bone, characterized by impairments commonly resulting in short stature, altered movement biomechanics, pain, fatigue and reduced functional performance. While current tools quantify functional mobility performance, they have not been standardly used in this population group and do not capture patient-reported symptoms such as pain or fatigue. This study evaluated a new tool, the Screening Tool for Everyday Mobility and Symptoms (STEMS), designed to accurately and objectively assess functional mobility and associated symptomology for individuals with skeletal dysplasia., Methods: Individuals aged 5-75 years with a skeletal dysplasia completed the STEMS, the Functional Mobility Scale (FMS) and Six Minute Walk Test (6MWT). The correlation among the STEMS, use of mobility aides, FMS and 6MWT normalised for leg length was calculated. One-way analysis of variance compared the STEMS symptomatology to normalised 6MWT distance., Results: One hundred and fifty individuals with skeletal dysplasia (76 achondroplasia, 42 osteogenesis imperfecta, 32 other; 74 < 18 years, 76 ≥ 18 years) participated. Almost two thirds of the group reported pain and/or fatigue when mobilising at home, at work or school and within the community, but only twenty percent recorded use of a mobility device. The STEMS setting category demonstrated highly significant correlations with the corresponding FMS category (r = - 0.983 to - 0.0994, all p < 0.001), and a low significant correlation with the normalised 6MWT distance (r = - 0.323 to - 0.394, all p < 0.001). A decreased normalised 6MWT distance was recorded for individuals who reported symptoms of pain and/or fatigue when mobilising at home or at work/school (all p ≤ 0.004). Those who reported pain only when mobilising in the community had a normal 6MWT distance (p = 0.43-0.46)., Conclusions: The Screening Tool for Everyday Mobility and Symptoms (STEMS) is a useful new tool to identify and record mobility aide use and associated self-reported symptoms across three environmental settings for adults and children with skeletal dysplasia. The STEMS may assist clinicians to monitor individuals for changes in functional mobility and symptoms over time, identify individuals who are functioning poorly compared to peers and need further assessment, and to measure effectiveness of treatment interventions in both clinical and research settings.

Participation, defined as 'involvement in life situations' according to the World Health Organisation, is a well-recognized concept and critical indicator of quality of life. In addition it has become an important outcome measure in child rehabilitation. However, little is known about the level of participation of young children with Developmental Disabilities. The aim of this study was to capture their subjective experiences of participation. An adapted informed consent based on a comic strip was used to get the children's assent. A Photo Elicitation study was used, in which photographs were taken by the children when they were involved in meaningful activities. The photographs were then used to facilitate communication with the children and to initiate in depth-interviews. Forty-seven interviews with 16 children between five and nine years were conducted based on their photographs. This method generated rich data, confirming that young children with Developmental Disabilities were able to inform us accurately on their experiences of participation. Data was analysed by means of an inductive thematic analysis. Results showed that children perceived their participation as satisfying when they can play, learn and join in family gatherings resulting in feelings of inclusion, recognition and belonging. When there are-on occasions-moments that their participation was obstructed, the children used two strategies to resolve it. Or they walked away from it and choose not to participate, or when autonomously motivated for the activity, they relied primarily on their context (i.e. mothers) as enabling their participation. Related to the data, children discussed themes related to their person, activities, connections and mediators between those themes. These themes fit well within earlier and current research on the subject of participation., Competing Interests: The authors have declared that no competing interests exist.

Background: During the early years of a child's life, participation is essential for learning and development. Children with disabilities are at risk for decreased participation. The interplay between environment and participation is identified as one of the most important factors influencing successful participation. The objective of this scoping review was to synthesize peer-reviewed literature about barriers and facilitators of participation according to the perspective of parents of children younger than 6 years with Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and/ or Developmental Coordination Disorder (DCD)., Methods: The scoping review followed Arksey and O'Malley's framework. Relevant studies were identified by a comprehensive search of scientific databases (PubMed and Web of Science). Studies describing perspectives of parents regarding their child's participation, written in English, and published between 2001 and September 2017 were included., Results: A total of 854 articles were retrieved, with 13 meeting the criteria. Elements contributing to perceived barriers and facilitators were identified and organized according to the International Classification of Functioning, Child-Youth framework. Concepts contained in these studies were linked to "activities and participation" (general tasks and demands, such as bedtime and dinner routines, and social, civic life, such as play and leisure). Environment-focused factors identified were situated on "support and relationships, " "attitudes, " and "services, systems, and policies.", Conclusion: The review revealed guidelines focusing on family-centred care, communication with, and providing information to parents with young children with developmental disabilities (ADHD, DCD, and/ or ASD)., (© 2019 John Wiley & Sons Ltd.)

Objectives To synthesize the evidence on the psychometrics functional capacity evaluation (FCE) methods. Methods A systematic literature search in nine databases. The resulting articles were screened based on predefined in- and exclusion criteria. Two reviewers independently performed this screening. Included studies were appraised based on their methodological quality. Results The search resulted in 20 eligible studies about nine different FCE methods. The Baltimore Therapeutic Equipment work simulator showed a moderate predictive validity. The Ergo-Kit (EK) showed moderate variability and high inter- and intra-rater reliability. Low discriminative abilities and high convergent validity were found for the EK. Concurrent validity of the EK and the ERGOS Work Simulator was low to moderate. Moderate to high test-retest, inter- and intra-reliability was found in the Isernhagen Work-Systems (IWS) FCE. The predictive validity of the IWS was low. The physical work performance evaluation (PWPE) showed moderate test-retest reliability and moderate to high inter-rater reliability. Low internal and external responsiveness were found for the PWPE, predictive validity was high. The predictive validity of the short-form FCE was also high but need to be further examined on several psychometric properties. Low discriminative and convergent validity were found for the work disability functional assessment battery. The WorkHab showed moderate to high test-retest, inter- and intra-rater reliability. Conclusion Well-known FCE methods have been rigorously studied, but some of the research indicates weaknesses in their reliability and validity. Future research should address how these weaknesses can be overcome.

Background: Rehabilitation services are increasingly targeting involvement in daily life. In the International Classification of Functioning, Disability and Health this is referred to as "participation". How-ever, questions have arisen regarding the conceptualization of participation, and consensus is lacking., Methods: The first phase of this study is a critical review of the literature to detect recurring conceptual problems in the application of participation and how researchers deal with these. The second phase is a systematic review to identify how participation measures are operationalized., Results: The critical review found possible solutions to 4 recurring key limitations: (i) how to deal with ambiguity and vagueness regarding the term "participation"; (ii) how to differentiate between activity and participation; (iii) what is the current empirical knowledge about the subjective aspects of participation; (iv) what are the different ways to measure participation. The systematic review found 18 instruments operationalizing participation in different ways: (i) unidimensional: frequency of performing activities; (ii) unidimensional: limitations in experiencing participation when performing activities; (iii) multidimensional: multiple subjective dimensions when performing activities; and (iv) multidimensional: objective and subjective dimensions., Discussion and Conclusion: Notwithstanding an increasing body of knowledge, some issues remain unclear and how participation is measured is subject to debate. This results in difficulties in the use of participation in clinical practice. However, insight into the current body of knowledge and awareness of shortcomings might help clinicians who aim to apply participation in practice.

Objective: Motivation is suggested as an important factor in pediatric motor rehabilitation. Therefore, we reviewed the existing evidence of (motivational) motor rehabilitation paradigms, and how motivation influences rehabilitation outcome using self-determination theory as conceptual framework., Methods: PubMed and Web-of-Science databases were systematically searched until June 2015. Data were independently extracted and critiqued for quality by three authors. Studies reporting motivational aspects were included. Most studies examined new technology (e.g., virtual reality [VR])., Results: Out of 479 records, three RCT, six case-control, and six non-comparative studies were included with mixed quality. Motivation was rarely reported. Training individualization to the child's capabilities with more variety seemed promising to increase motivation. Motivation increased when the exercises seemed helpful for daily activities., Conclusions: Motivation in pediatric rehabilitation should be comprehensively assessed within a theoretical framework as there are indications that motivated children have better rehabilitation outcomes, depending on the aspect of motivation.

Many DNA lesions associated with lymphoid malignancies are linked to off-target cleavage by the RAG1/2 recombinase. However, off-target cleavage has mostly been analyzed in the context of DNA repair defects, confounding any mechanistic understanding of cleavage deregulation. We identified a conserved SQ phosphorylation site on RAG2 365 to 366 that is involved in feedback control of RAG cleavage. Mutation of serine 365 to a non-phosphorylatable alanine permits bi-allelic and bi-locus RAG-mediated breaks in the same cell, leading to reciprocal translocations. This phenomenon is analogous to the phenotype we described for ATM kinase inactivation. Here, we establish deregulated cleavage itself as a driver of chromosomal instability without the associated repair defect. Intriguingly, a RAG2-S365E phosphomimetic rescues the deregulated cleavage of ATM inactivation, reducing the incidence of reciprocal translocations. These data support a model in which feedback control of cleavage and maintenance of genome stability involves ATM-mediated phosphorylation of RAG2., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The consequences of the Ehlers-Danlos Syndrome hypermobility type (EDS-HT) affect many aspects of daily life. "Living with limitations" is a central theme in the life of patients affected by this heritable disorder of connective tissue. The aim of the present study was to explore the lived experiences of women with EDS-HT concerning diagnosis, influence on daily life and becoming and being a mother., Method: A phenomenological-hermeneutical study, using in-depth interviews. Patients were selected by a purposive sampling strategy., Results: This study shows that the EDS-HT syndrome affects daily life. Ten woman between 31 and 65 years were interviewed. They have between 2 and 5 children. The data analysis results in six themes. (1) Getting a diagnosis is a relief and supports the choice to become a mother; (2) EDS-HT causes emotional distress, imposes a physical burden and has a major impact on social behavior; (3) EDS-HT demands a restructuring of everyday activities; (4) Children's and mothers' expectations do not correspond; (5) Having a supportive social and physical environment is of major importance; (6) The presence of the child reduces the feeling of illness of the mother., Conclusion: The diagnosis of EDS-HT is a catalysing factor in the choice of whether or not to become a mother. EDS-HT has a huge impact on bodily functions, which in turn influences activities and participation., Implications: This study gives insight in the activities of daily life of persons with EDS-HT. Health care professionals can be of great importance to help patients in (re)organizing their lives according to the available energy and in supporting their choices. They can help defining goals and setting priorities in daily life., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The overexpression of microRNA cluster miR-17-92 has been implicated in development of solid tumors and hematological malignancies. The role of miR-17-92 in lymphomagenesis has been extensively investigated; however, because of the developmental defects caused by miR-17-92 dysregulation, its ability to drive tumorigenesis has remained undetermined until recently. Here we demonstrate that overexpression of miR-17-92 in a limited number of hematopoietic cells is sufficient to cause B cell malignancies. In sum, our study provides a novel and physiologically relevant model that exposes the potent ability of miR-17-92 to act as a driver of tumorigenesis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Misrepair of DNA double-strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin (Ig) and T cell receptor (Tcr) loci has been implicated in pathogenesis of lymphoid malignancies in humans and in mice. Defects in DNA damage response factors such as ataxia telangiectasia mutated (ATM) protein and combined deficiencies in classical non-homologous end joining and p53 predispose to RAG-initiated genomic rearrangements and lymphomagenesis. Although we showed previously that RAG1/RAG2 shepherd the broken DNA ends to classical non-homologous end joining for proper repair, roles for the RAG proteins in preserving genomic stability remain poorly defined. Here we show that the RAG2 carboxy (C) terminus, although dispensable for recombination, is critical for maintaining genomic stability. Thymocytes from 'core' Rag2 homozygotes (Rag2(c/c) mice) show dramatic disruption of Tcrα/δ locus integrity. Furthermore, all Rag2(c/c) p53(-/-) mice, unlike Rag1(c/c) p53(-/-) and p53(-/-) animals, rapidly develop thymic lymphomas bearing complex chromosomal translocations, amplifications and deletions involving the Tcrα/δ and Igh loci. We also find these features in lymphomas from Atm(-/-) mice. We show that, like ATM-deficiency, core RAG2 severely destabilizes the RAG post-cleavage complex. These results reveal a novel genome guardian role for RAG2 and suggest that similar 'end release/end persistence' mechanisms underlie genomic instability and lymphomagenesis in Rag2(c/c) p53(-/-) and Atm(-/-) mice.

In various types of stem cells, including embryonic stem (ES) cells and hematopoietic stem cells, telomerase functions to ensure long-term self-renewal capacity via maintenance of telomere reserve. Expression of the catalytic component of telomerase, telomerase reverse transcriptase (Tert), which is essential for telomerase activity, is limiting in many types of cells and therefore plays an important role in establishing telomerase activity levels. However, the mechanisms regulating expression of Tert in cells, including stem cells, are presently poorly understood. In the present study, we sought to identify genes involved in the regulation of Tert expression in stem cells by performing a screen in murine ES (mES) cells using a shRNA expression library targeting murine transcriptional regulators. Of 18 candidate transcriptional regulators of Tert expression identified in this screen, only one candidate, hypoxia inducible factor 1 alpha (Hif1alpha), did not have a significant effect on mES cell morphology, survival, or growth rate. Direct shRNA-mediated knockdown of Hif1alpha expression confirmed that suppression of Hif1alpha levels was accompanied by a reduction in both Tert mRNA and telomerase activity levels. Furthermore, gradual telomere attrition was observed during extensive proliferation of Hif1alpha-targeted mES cells. Switching Hif1alpha-targeted mES cells to a hypoxic environment largely restored Hif1alpha levels, as well as Tert expression, telomerase activity levels, and telomere length. Together, these findings suggest a direct effect of Hif1alpha on telomerase regulation in mES cells, and imply that Hif1alpha may have a physiologically relevant role in maintenance of functional levels of telomerase in stem cells.

The role of axial structures, especially the notochord, in metanephric kidney development has not been directly examined. Here, we showed that disruption of the notochord and floor plate by diphtheria toxin (DTA)-mediated cell ablation did not disrupt nephrogenesis, but resulted in kidney fusions, resembling horseshoe kidneys in humans. Axial disruptions led to more medially positioned metanephric mesenchyme (MM) in midgestation. However, neither axial disruption nor the ensuing positional shift of the MM affected the formation of nephrons and other structures within the kidney. Response to Shh signaling was greatly reduced in midline cell populations in the mutants. To further ascertain the molecular mechanism underlying these abnormalities, we specifically inactivated Shh in the notochord and floor plate. We found that depleting the axial source of Shh was sufficient to cause kidney fusion, even in the presence of the notochord. These results suggested that the notochord is dispensable for nephrogenesis but required for the correct positioning of the metanephric kidney. Axial Shh signal appears to be critical in conferring the effects of axial structures on kidney positioning along the mediolateral axis. These studies also provide insights into the pathogenesis of horseshoe kidneys and how congenital kidney defects can be caused by signals outside the renal primordia., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

A prospective, cross-sectional, observational study in preterm and term infants was performed to compare multimodal measurements of body composition, namely, limb ultrasound, bone quantitative ultrasound, and dual X-ray absorptiometry (DXA). One hundred and two preterm and term infants appropriate for gestational age were enrolled from the newborn nursery and neonatal intensive care unit. Infants were included when they were medically stable, in an open crib, on full enteral feeds and within 1 week of anticipated discharge. Correlations among the various measurements of body composition were performed using standard techniques. A comparison between preterm infant (born at 28-32 weeks) reaching term to term-born infants was performed. Limb ultrasound estimates of cross-sectional areas of lean and fat tissue in a region of tissue (i.e., the leg) were remarkably correlated with regional and whole-body estimates of fat-free mass and fat obtained from DXA suggesting the potential usefulness of muscle ultrasound as an investigative tool for studying aspects of body composition in this fragile population. There was a weak but significant correlation between quantitative ultrasound measurements of bone strength and DXA-derived bone mineral density (BMD). Preterm infants reaching term had significantly lower body weight, length, head circumference, muscle and fat cross-sectional area, bone speed of sound, whole-body and regional lean body mass, fat mass, and BMD compared to term-born infants. Current postnatal care and nutritional support in preterm infants is still unable to match the in-utero environment for optimal growth and bone development. The use of relatively simple bedside, noninvasive body composition measurements may assist in understanding how changes in different components of body composition early in life affect later growth and development., (2009 Wiley-Liss, Inc.)

Tbx18 is a T-Box transcription factor that has specific expression and indispensible function in the lower urinary tract. Here, we report the generation and characterization of a bacterial artificial chromosome (BAC) transgene expressing Cre under the control of Tbx18 regulatory elements. When crossed to the ROSA26R-lacZ reporter mice, the Tbx18-Cre transgene mediates loxP recombination in the mesenchymal derivatives in the lower urinary tract, especially in the smooth muscle cells (SMCs) and the stromal cells. There is no expression of this transgene in the urothelium or in the kidney. This Tbx18-Cre transgene recapitulates the endogenous Tbx18 expression in the urinary system and can be used for the study of the development, physiology, and diseases in the urinary tract. Its additional expression in the epicardium, limb, vibrissae, and other structures would be useful for studies in the relevant fields., (Copyright 2009 Wiley-Liss, Inc.)

In mammals, Sirt1, a member of the sirtuin family of proteins, functions as a nicotinamide adenine dinucleotide-dependent protein deactylase, and has important physiological roles, including the regulation of glucose metabolism, cell survival, and mitochondrial respiration. The initial investigations of Sirt1 deficient mice have revealed a phenotype that includes a reduced lifespan, small size, and an increased frequency of abnormal sperm. We have now performed a detailed analysis of the molecular and functional effects of Sirt1 deficiency in the germ line of Sirt1 knock-out (-/-) mice. We find that Sirt1 deficiency markedly attenuates spermatogenesis, but not oogenesis. Numbers of mature sperm and spermatogenic precursors, as early as d15.5 of development, are significantly reduced ( approximately 2-10-fold less; P

Telomere length maintenance in the germ line from generation to generation is essential for the perpetuation of eukaryotic organisms. This task is performed by a specialized reverse transcriptase called telomerase. While this critical function of telomerase has been well established, the mechanisms that regulate telomerase in the germ line are still poorly understood. We now show, using a Pou5f1-GFP transgenic mouse model, that telomerase suppression in quiescent male primordial germ cells (PGCs) is accompanied by a decrease in expression of murine telomerase reverse transcriptase (TERT). To further assess the role of TERT in quiescent PGCs, we developed a chicken Actb gene promoter/cytomegalovirus enhancer (CAG)-Tert transgenic mouse strain that constitutively expresses murine TERT. Telomerase activity was detected in quiescent PGCs from CAG-Tert transgenic embryos, demonstrating that re-activation of TERT expression is sufficient to restore telomerase activity in these cells and implying that TERT expression is an important mechanism of telomerase regulation in PGCs. Fluorescence-activated cell-sorting (FACS) analysis of PGC frequency and cell cycle status revealed no effect of either overexpression or deficiency of TERT in CAG-Tert transgenic mice or Tert knock-out mice respectively. These results demonstrate that TERT per se does not affect proliferation or development of PGCs, in contrast with recent studies that suggest that TERT has a telomere-independent effect in certain stem cells. It is possible that the direct effect of TERT on cell behavior may be dependent on cell type.