Effectiveness of Neuromotor Task Training for Children with Developmental Coordination Disorder: A Pilot Study

The aim of this pilot study was to evaluate the effectiveness of a Neuromotor Task Training (NTT), recently developed for the treatment of children with Developmental Coordination Disorder (DCD) by pediatric physical therapists in the Netherlands. NTT is a task-oriented treatment program based upon recent insights from motor control and motor learning research. Ten children with DCD (intervention group) were tested before and after 9 and 18 treatment sessions on the Movement ABC and a dysgraphia scale in order to measure the effectiveness of treatment on gross and fine motor skills in general and handwriting in particular. Five children (no-treatment control group) were tested twice with a time lag of nine weeks on the Movement ABC in order to measure spontaneous improvement. No improvement was measured for the children in the notreatment control group, whereas a significant improvement was found for children in the intervention group for both quality of handwriting and performance on the Movement ABC after 18 treatment sessions

Peptides from chiral Calpha,alpha-disubstituted glycines : crystallographic characterization of conformation of Calpha-methyl, Calpha-isopropylglycine [(alphaMe)Val] in simple derivatives and model peptides

The mol. and crystal structures of R-L-(aMe)Val-R1 [R = ClCH2CO, R1 = OH; R = Z, R1 = Ala-Ala-OMe (I); R = Ac-Aib-Aib, Z-Aib, R1 = Aib-Aib-OCMe3; (aMe)Val = NHCMe(CHMe2)CO; Z = PhCH2O2C; Aib = NHCMe2CO] were detd. by x-ray diffraction. Tripeptide I adopts a type-I b-turn conformation stabilized by a

Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT)

Polymeric cytotoxic conjugates are being developed with the aim of preferential delivery of the anticancer agent to tumour. MAG-CPT comprises the topoisomerase I inhibitor camptothecin linked to a water-soluble polymeric backbone methacryloylglycynamide ( average molecular weight 18 kDa, 10% CPT by weight). It was administered as a 30-min infusion once every 4 weeks to patients with advanced solid malignancies. The objectives of our study were to determine the maximum tolerated dose, dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document responses to this treatment. The starting dose was 30 mgm(-2) (dose expressed as mg equivalent camptothecin). In total, 23 patients received 47 courses at six dose levels, with a maximum dose of 240 mgm(-2). Dose-limiting toxicities were myelosuppression, neutropaenic sepsis, and diarrhoea. One patient died after cycle 1 MAG-CPT at the maximum dose. The maximum tolerated dose and dose recommended for further clinical study was 200 mgm(-2). The half-lives of both MAG-CPT and released CPT were prolonged (46 days) and measurable levels of MAG-CPT were retrieved from plasma and urine 4 weeks after treatment. However, subsequent pharmacodynamic studies of this agent have led to its withdrawal from clinical development

Geophysical studies with laser-beam detectors of gravitational waves

The existing high technology laser-beam detectors of gravitational waves may find very useful applications in an unexpected area - geophysics. To make possible the detection of weak gravitational waves in the region of high frequencies of astrophysical interest, ~ 30 - 10^3 Hz, control systems of laser interferometers must permanently monitor, record and compensate much larger external interventions that take place in the region of low frequencies of geophysical interest, ~ 10^{-5} - 3 X 10^{-3} Hz. Such phenomena as tidal perturbations of land and gravity, normal mode oscillations of Earth, oscillations of the inner core of Earth, etc. will inevitably affect the performance of the interferometers and, therefore, the information about them will be stored in the data of control systems. We specifically identify the low-frequency information contained in distances between the interferometer mirrors (deformation of Earth) and angles between the mirrors' suspensions (deviations of local gravity vectors and plumb lines). We show that the access to the angular information may require some modest amendments to the optical scheme of the interferometers, and we suggest the ways of doing that. The detailed evaluation of environmental and instrumental noises indicates that they will not prevent, even if only marginally, the detection of interesting geophysical phenomena. Gravitational-wave instruments seem to be capable of reaching, as a by-product of their continuous operation, very ambitious geophysical goals, such as observation of the Earth's inner core oscillations.Comment: 29 pages including 8 figures, modifications and clarifications in response to referees' comments, to be published in Class. Quant. Gra

Rare musculoskeletal diseases in adults: a research priority setting partnership with the James Lind Alliance

Background Osteogenesis imperfecta, fibrous dysplasia/McCune-Albright syndrome and X-linked hypophosphatemia are three rare musculoskeletal diseases characterised by bone deformities, frequent fractures and pain. Little high-quality research exists on appropriate treatment and long-term management of these conditions in adults. This is further worsened by limited research funding in rare diseases and a general mismatch between the existing research priorities and those of the patients. This partnership adopted the James Lind Alliance approach to identify the top 10 research priorities for rare musculoskeletal diseases in adults through joint patient, carer and healthcare professional collaboration. Results The initial survey for question collection recruited 198 respondents, submitting a total of 988 questions. 77% of the respondents were patients with a rare musculoskeletal disease. Following out-of-scope question exclusion, repeating query grouping and scientific literature check for answers, 39 questions on treatment and long-term management remained. In the second public survey, 220 respondents, of whom 85% were patients with a rare musculoskeletal disease, their carers, relatives or friends, prioritised these uncertainties, which allowed selection of the top 25. In the last stage, patients, carers and healthcare professionals gathered for a priority setting workshop to reach a consensus on the final top 10 research priorities. These focus on the uncertainties surrounding appropriate treatment and holistic long-term disease management, highlighting several aspects indirect to abnormal bone metabolism, such as extra-skeletal symptoms, psychological care of both patients and their families and disease course through ageing. Conclusions This James Lind Alliance priority setting partnership is the first to investigate rare bone diseases. The priorities identified here were developed jointly by patients, carers and healthcare professionals. We encourage researchers, funding bodies and other stakeholders to use these priorities in guiding future research for those affected by rare musculoskeletal disorders

Optimal design of thermally stable proteins

Motivation: For many biotechnological purposes, it is desirable to redesign proteins to be more structurally and functionally stable at higher temperatures. For example, chemical reactions are intrinsically faster at higher temperatures, so using enzymes that are stable at higher temperatures would lead to more efficient industrial processes. We describe an innovative and computationally efficient method called Improved Configurational Entropy (ICE), which can be used to redesign a protein to be more thermally stable (i.e. stable at high temperatures). This can be accomplished by systematically modifying the amino acid sequence via local structural entropy (LSE) minimization. The minimization problem is modeled as a shortest path problem in an acyclic graph with nonnegative weights and is solved efficiently using Dijkstra's method

Modelling charge self-trapping in wide-gap dielectrics: Localization problem in local density functionals

We discuss the adiabatic self-trapping of small polarons within the density functional theory (DFT). In particular, we carried out plane-wave pseudo-potential calculations of the triplet exciton in NaCl and found no energy minimum corresponding to the self-trapped exciton (STE) contrary to the experimental evidence and previous calculations. To explore the origin of this problem we modelled the self-trapped hole in NaCl using hybrid density functionals and an embedded cluster method. Calculations show that the stability of the self-trapped state of the hole drastically depends on the amount of the exact exchange in the density functional: at less than 30% of the Hartree-Fock exchange, only delocalized hole is stable, at 50% - both delocalized and self-trapped states are stable, while further increase of exact exchange results in only the self-trapped state being stable. We argue that the main contributions to the self-trapping energy such as the kinetic energy of the localizing charge, the chemical bond formation of the di-halogen quasi molecule, and the lattice polarization, are represented incorrectly within the Kohn-Sham (KS) based approaches.Comment: 6 figures, 1 tabl

Motor coordination problems in children and adolescents with ADHD rated by parents and teachers: effects of age and gender

Summary. Objective. ADHD is frequently accompanied by motor coordination problems. However, the co-occurrence of poor motor performance has received less attention in research than other coexisting problems in ADHD. The underlying mechanisms of this association remain unclear. Therefore, we investigated the prevalence of motor coordination problems in a large sample of children with ADHD, and the relationship between motor coordination problems and inattentive and hyperactive/impulsive symptoms. Furthermore, we assessed whether the association between ADHD and motor coordination problems was comparable across ages and was similar for both genders. Method. We investigated 486 children with ADHD and 269 normal controls. Motor coordination problems were rated by parents (Developmental Coordination Disorder Questionnaire) and teachers (Groningen Motor Observation Scale). Results. Parents and teachers reported motor coordination problems in about one third of children with ADHD. Problems of fine and gross motor skills, coordination skills and motor control were all related to inattentive rather than hyperactive/impulsive symptoms. Relative to controls, motor coordination problems in ADHD were still present in teenagers according to parents; the prevalence diminished somewhat according to teachers. Boys and girls with ADHD were comparably affected, but motor performance in controls was better in girls than in boys. Conclusions. Motor coordination problems were reported in one third of children with ADHD and affected both boys and girls. These problems were also apparent in adolescents with ADHD. Clinicians treating children with ADHD should pay attention to co-occurring motor coordination problems because of the high prevalence and the negative impact of motor coordination problems on daily life