Impaired Cognitive Functioning in Patients with Tyrosinemia Type I Receiving Nitisinone

ObjectiveTo examine cognitive functioning in patients with tyrosinemia type I treated with nitisinone and a protein-restricted diet.Study designWe performed a cross-sectional study to establish cognitive functioning in children with tyrosinemia type I compared with their unaffected siblings. Intelligence was measured using age-appropriate Wechsler Scales. To assess cognitive development over time, we retrieved sequential IQ scores in a single-center subset of patients. We also evaluated whether plasma phenylalanine and tyrosine levels during treatment was correlated with cognitive development.ResultsAverage total IQ score in 10 patients with tyrosinemia type I receiving nitisinone was significantly lower compared with their unaffected siblings (71 ± 13 vs 91 ± 13; P = .008). Both verbal and performance IQ subscores differed (77 ± 14 vs 95 ± 11; P < .05 and 70 ± 11 vs 87 ± 15; P < .05, respectively). Repeated IQ measurements in a single-center subset of 5 patients revealed a decline in average IQ score over time, from 96 ± 15 to 69 ± 11 (P < .001). No significant association was found between IQ score and either plasma tyrosine or phenylalanine concentration.ConclusionPatients with tyrosinemia type I treated with nitisinone are at risk for impaired cognitive function despite a protein-restricted diet

Long-term psychosocial functioning after Ilizarov limb lengthening during childhood: 37 patients followed for 2–14 years

Background and purpose Few studies have been concerned with the patient's perception of the outcome of limb lengthening. We describe the psychological and social functioning after at least 2 years of follow-up in patients who had had a leg length discrepancy and who had undergone an Ilizarov limb lengthening procedure

Motives for choosing growth-enhancing hormone treatment in adolescents with idiopathic short stature: a questionnaire and structured interview study

Background Growth-enhancing hormone treatment is considered a possible intervention in short but otherwise healthy adolescents. Although height gain is an obvious measure for evaluating hormone treatment, this may not be the ultimate goal for the person, but rather a means to reach other goals such as the amelioration of current height-related psychosocial problems or the enhancement of future prospects in life and society. The aim of our study was to clarify the motives of adolescents and their parents when choosing to participate in a growth-enhancing trial combining growth hormone and puberty-delaying hormone treatment. Methods Participants were early pubertal adolescents (25 girls, 13 boys) aged from 11 to 13 years (mean age 11.5 years) with a height standard deviation score (SDS) ranging from -1.03 to -3.43. All had been classified as idiopathic short stature or persistent short stature born small for the gestational age (intrauterine growth retardation) on the basis of a height SDS below -2, or had a height SDS between -1 and -2 and a predicted adult height SDS below -2. The adolescents and their parents completed questionnaires and a structured interview on the presence of height-related stressors, parental worries about their child's behavior and future prospects, problems in psychosocial functioning, and treatment expectations. Questionnaire scores were compared to norms of the general Dutch population. Results The adolescents reported normal psychosocial functioning and highly positive expectations of the treatment in terms of height gain, whereas the parents reported that their children encountered some behavioral problems (being anxious/depressed, and social and attention problems) and height-related stressors (being teased and juvenilized). About 40% of the parents were worried about their children's future prospects for finding a spouse or job. The motives of the adolescents and their parents exhibited rather different profiles. The most prevalent parental worries related to the current or future functioning of their children, while a few cases were characterized by no observed motives or by psychosocial problems only reported by the adolescents themselves. Conclusion The motives for participating in a growth-enhancing hormone trial are more obvious in the parents than in the adolescents themselves. Two out of three parents report worries about the future opportunities or observe modest current psychosocial problems in their children. The adolescents want to gain height, but the motivation underlying this remains unclear. Few of the adolescents experience psychosocial problems. Our analyses revealed differences among individuals in terms of motives, which implies that in an evaluation of hormone treatment, the importance of divergent outcome variables will also differ among individuals. Effectiveness evaluations of hormone treatment to increase height and the consequential fulfillment of other goals must be awaited

Design of the Quality of Life in Motion (QLIM) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of a combined physical exercise and psychosocial training program to improve physical fitness in children with cancer

<p>Abstract</p> <p>Background</p> <p>Childhood cancer and its treatment have considerable impact on a child's physical and mental wellbeing. Especially long-term administration of chemotherapy and/or radiotherapy impairs physical fitness both during and after therapy, when children often present with muscle weakness and/or low cardiorespiratory fitness. Physical exercise can improve these two elements of physical fitness, but the positive effects of physical exercise might be further increased when a child's wellbeing is simultaneously enhanced by psychosocial training. Feeling better may increase the willingness and motivation to engage in sports activities. Therefore, this multi-centre study evaluates the short and long-term changes in physical fitness of a child with a childhood malignancy, using a combined physical exercise and psychosocial intervention program, implemented during or shortly after treatment. Also examined is whether positive effects on physical fitness reduce inactivity-related adverse health problems, improve quality of life, and are cost-effective.</p> <p>Methods</p> <p>This multi-centre randomized controlled trial compares a combined physical and psychosocial intervention program for children with cancer, with care as usual (controls). Children with cancer (aged 8-18 years) treated with chemotherapy and/or radiotherapy, and who are no longer than 1 year post-treatment, are eligible for participation. A total of 100 children are being recruited from the paediatric oncology/haematology departments of three Dutch university medical centres. Patients are stratified according to pubertal stage (girls: age ≤10 or >10 years; boys: ≤11 or >11 years), type of malignancy (haematological or solid tumour), and moment of inclusion into the study (during or after treatment), and are randomly assigned to the intervention or control group.</p> <p>Discussion</p> <p>Childhood cancer patients undergoing long-term cancer therapy may benefit from a combined physical exercise and psychosocial intervention program since it may maintain or enhance their physical fitness and increase their quality of life. However, the feasibility, patient need, and effectiveness of such a program should be established before the program can be implemented as part of standard care.</p> <p>Trial registration number</p> <p>NTR1531 (The Netherlands National Trial Register)</p

Risk Factors for Persistent Fatigue With Significant School Absence in Children and Adolescents

OBJECTIVE: To assess children and adolescents with severe fatigue who are referred to pediatricians and to examine whether factors can be identified at their first visit that predict worse outcomes at 1 year. METHODS: Ninety-one patients, aged 8 to 18 years completed questionnaires about sleep, somatic symptoms, physical activity, and fatigue. They were reassessed 12 months later. Measurements at baseline and outcome were analyzed by using univariable logistic regression with persistent, severe fatigue (yes/no) and persistent school absence (yes/no) as dependent variables and baseline scores as independent variables. RESULTS: After 12 months, 50.6% of the children and adolescents showed improvement; 29.1% had persistent fatigue, and 20.3% had persistent fatigue with significant school absence. Factors associated with the poorest outcome were sleep problems (odds ratio [OR]: 1.4 [95% confidence interval (CI): 1.1-1.8]), initial fatigue score (OR: 1.1 [95% CI: 1.0-1.2]), somatic complaints such as hot and cold spells (OR: 1.9 [95% CI: 1.2-3.0]), blurred vision ( OR: 2.1 [95% CI: 1.1-4.0]), pain in arms and legs (OR: 2.0 [95% CI: 1.0-3.2]), back pain (OR: 1.8 [95% CI: 1.0-3.2]), constipation ( OR: 1.7 [95% CI: 1.0-2.7]), and memory deficits (OR: 1.8 [95% CI: 1.0-3.2]). Resolved fatigue was associated with male gender (OR: 5.0 [95% CI: 1.6-15.5]) and a physically active lifestyle (OR: 1.3 [95% CI: 1.1-1.5]). CONCLUSIONS: Assessment of predictive factors at the first visit enables the pediatrician to identify those patients with severe fatigue who are at risk of a poor outcome. Female gender, poor sleep quality, physically inactive lifestyle, and specific somatic complaints were important predictive factors. Pediatrics 2009; 124: e89-e9

Microstructure and Properties of AA 2195 T8 Material and Friction Stir Welds

The study shows the main properties of AA2195 in relation to the microstructure developing in the friction stir weld process, which were comprehensively investigated in the ESA Technology and Research Programme Damage Tolerance of Cryogenic Pressure Vessels (TRP T401-02 MC). Friction Stir Welding (FSW) on 5 mm sheets of AA2195 in T8 condition was performed and process parameters were optimized. Non-destructive Inspection (NDI) methods were used to detect potential defects and metallographic investigations were applied in order to detect their origin. The properties on the friction stir joints were determined and the influence of temperature down to 20 K is shown. Particular attention is given to the microstructure and the fracture characteristics of the friction stir welds and base material. Optical and scanning electron microscopy investigations are used to determine the failure mode. Additionally, the influence of temperature is discussed on the basis of samples fractured at RT, 77 K, 20 K and 4 K. The metallographic analysis of NDI results of friction stir welds indicates that a thorough process control can avoid the main large defects in FS welds. High strength FSW joints of AA2195 can be achieved with promising toughness down to cryogenic temperatures. The potential for the application in future launcher systems is discussed with respect to potential future serial production

Self-investigation to explore the impact of juvenile arthritis on adolescent life: A case-study

Objective: To gain insight into the personal experience and feelings of an adolescent with a chronic disease. Methods: We report on the application of the self-confrontation method (SCM), illustrated by a case-example of an adolescent with juvenile idiopathic arthritis. Results: Although taken at face value she was not impeded by the arthritis, through self-assessment with the SCM this adolescent acknowledged and addressed the emotional struggle to keep the arthritis secret and to constantly test the physical limits of her body. After the process of self-reflection, the adolescent showed a better integration of her arthritis experiences into her life story. Conclusion: With the SCM the adolescent could explore her own functioning and well-being on a manifest, as well as on an emotional and motivational level. Practice implications: In future research, by studying the self-investigations of a group of adolescents with chronic diseases, common risk factors for the development of a stable identity during adolescence might be identified. In clinical care, the SCM promotes self-knowledge, allowing for an intrinsic motivation to deal with the emotional impact of the disease

The views of young adults and their parents on hormone treatment for short stature in adolescence

Aim: To examine the view of young adults and their parents on growth hormone (GH) and gonadotropin-releasing hormone agonist (GnRHa) treatment in adolescence for idiopathic short stature (ISS) or short stature born small for gestational age (SGA). Methods: Thirty young adults with ISS or SGA (18 treated, 12 untreated; age 17-23 years; 5.5 years after treatment) completed questionnaires and they and their parents were interviewed. Results: Self-perceived current psychosocial functioning did not differ between the treated and untreated young adults, but several treated participants perceived psychosocial problems during adolescence. Most treated participants would have chosen again to receive hormone treatment, but they mentioned disadvantages of the treatment and were, as well as untreated participants, reticent upon recommending hormone treatment to others. Conclusion: GH/GnRHa treatment did not appear to have adverse long-term psychosocial consequences and the participants were glad to have taken the opportunity to receive hormone treatment. However, the treated group mentioned several disadvantages of the treatment and perceived some height-related psychosocial problems during adolescence. In considering hormone treatment, the positive as well as the negative aspects of the treatment as perceived by the participants are to be taken into consideration. Copyright (c) 2008 S. Karger AG, Basel

ABOUT THE DEMISABILITY OF PROPELLANT TANKS DURING ATMOSPHERIC RE-ENTRY FROM LEO

The concern about the on-ground risk caused by spacecraft fragments surviving atmospheric re-entry has significantly grown during the past decade, resulting in numerous activities of the space community like re-entry simulation tool development, improvement, and validation, as well as research for design-for-demise (D4D). The purpose of the first group is to increase the confidence in numerical re-entry risk predictions, while the second activity aims to develop new spacecraft design techniques which are likely to improve the demise behavior significantly. Standard (Titanium) propellant tanks for LEO (Low Earth Orbit) missions appear regularly within the group of spacecraft (satellite) components causing the highest on-ground risk, i.e. in the order of 20% for a 1-ton class Earth observation satellite. Thus, tanks are one of the primary targets for any D4D activity. Various ideas for demisable propellant tank concepts have been published recently, including aluminum tanks (e.g. based on aluminum-lithium alloys) or composite tanks (e.g. Carbon-fiber overwrapped metallic liners). The demonstration of the actual demisability of such new tank concepts has turned out to be difficult, sometimes even questionable. Intensive laboratory tests in arc-jet heated or plasma wind-tunnels and laser facilities have provided extensive results. Numerical simulations have been conducted to reproduce these experimental findings. This paper will contain a critical review of the latest experimental and numerical results about the demisability of satellite propellant tanks during atmospheric re-entry from LEO

Behavior and development in children and age at the time of first anesthetic exposure

Several experimental studies have suggested that early exposure to anesthetic agents, i.e., before completion of synaptogenesis, can result in widespread apoptotic neuronal degeneration and late cognitive impairment, but human data are lacking. The authors performed a retrospective pilot study to test the feasibility and calculate sample sizes for a larger epidemiologic study of disturbed neurobehavioral development as a function of age at the time of first anesthetic exposure. Pediatric urological procedures were selected because the timing of surgery depends mainly on the age at which a diagnosis is made. Neurobehavioral development was assessed using the validated 120-item parental Child Behavior CheckList/4-18 in 314 children who were operated for pediatric urological procedures between the ages of 0 and 6 yr. Of 243 questionnaires returned, the total problem score was clinically deviant in 41 (23%) of children aged less than 24 months at the time of first surgery and 13 (20%) aged greater than 24 months. Crude and adjusted odds ratios for a clinically deviant Child Behavior CheckList/4-18 score increased with younger age at the time of surgery, but the confidence intervals were very wide. Adjusted odds ratio was 1.38 (0.59-3.22) when operated at age less than 6 months, 1.19 (0.45-3.18) when operated between 6 and 12 months of age, and 1.20 (0.45-3.20) when operated between 12 and 24 months (using operated at greater than 24 months of age as reference category). A properly powered cohort study would require at least 2,268 children. Children undergoing urologic surgery at age less than 24 months showed more behavioral disturbances than children in whom surgery was performed after age 2 yr, although the results were not statistically significant. To confirm or refute an effect of anesthesia on cognitive development, at least 2,268 children need to be studied. With retrospective study designs, residual confounding remains an issue that can only be solved in prospective randomized studie