Developmental Coordination Disorder and Unhealthy Weight Status in Taiwanese Children: The Roles of Sex and Age.

This study aimed to provide up-to-date information regarding the estimated prevalence of developmental coordination disorder (DCD) in Taiwanese children. Their unhealthy weight status was also examined, as well as the roles of sex and age. This cross-sectional study recruited 825 children aged between 4 and 12 years and categorized them into either typically developing children (TD, >16th percentile) or children at risk for DCD (rDCD, ≤16th percentile) based on the result of the Movement Assessment Battery for Children-2nd edition. Body mass index was calculated to determine weight status (i.e., normal weight, underweight, overweight, and obesity). The estimated prevalence of rDCD was 9.7%. There were significantly more boys in the rDCD groups (p < 0.001). Additionally, preschool children with rDCD were at greater risk for being underweight. However, there was no significant group difference which was found for overweight/obesity. A lower prevalence of rDCD was found in this study. Nevertheless, children with rDCD may be more likely to be underweight in early childhood. Early intervention should be provided to target this population.

Moderation of parental socioeconomic status on the relationship between birth health and developmental coordination disorder at early years.

Objective: This study investigated whether parental SES moderates the effect of birth health on Developmental Coordination Disorder (DCD) in preschool children. Methods: One hundred and twenty-two children aged 4 to 6 years were enrolled in the study. The Movement Assessment Battery for Children --2nd Edition (MABC-2) test was used to assess the motor coordination of children. They were preliminarily categorized into either the DCD (<=16th percentile, n = 23) or typically developing (TD) group (>16th percentile, n = 99) based on the testing results. All children in the DCD group were further confirmed to meet other diagnostic criteria of the DSM-V using the intellectual test and parental questionnaires. Moderation analysis was conducted using the PROCESS macro for SPSS, and 95% confidence intervals with a bootstrap procedure were calculated to identify the significant moderating effect. Results: Maternal education (unstandardized coefficient = 0.6805, SE = 0.3371, p < 0.05) and maternal employment status (unstandardized coefficient = 0.6100, SE = 0.3059, p < 0.05) were found to moderate the relationship between birth length and the probability of having DCD. Moreover, the relationship between birth weight and the probability of having DCD was moderated by the annual household income (unstandardized coefficient = -0.0043, SE = 0.0022, p < 0.05). Conclusion: The lower maternal education level and maternal unemployment strengthened the negative relationship between birth length and the probability of having DCD. Additionally, the negative relationship between birth weight and the probability of having DCD was statistically significant in high annual household salaries.

Axial rotation and pain are associated with facet joint osteoarthritis in adolescent idiopathic scoliosis.

OBJECTIVE: Facet joints are crucial for spinal stability but develop premature osteoarthritis in patients with adolescent idiopathic scoliosis (AIS). Here, we evaluated the association between facet joint cartilage and subchondral bone homeostasis, perceived back pain and 3-dimensional spinal deformity to better understand the role of facet joint degeneration in AIS progression and pain. METHOD: The osteoarthritic state of cartilage and bone of AIS facet joint surgical samples were characterized using histological OARSI scoring, visual morphological grading and µCT analysis, respectively. Back pain was self-reported using a numerical rating scale and expressed relative to the location on the patient's back. The scoliotic curves from our patient cohort were digitally reconstructed using biplanar radiographs and the eOS system (EOS imaging). The deformity was then reduced to three intervertebral angles (coronal, sagittal and axial) for each pair of bilateral facet joints. Statistical associations between the intervertebral angles, osteoarthritis parameters and pain intensity were performed using the Spearman method and Friedman test. RESULTS: Facet joint cartilage degeneration was associated with decreased subchondral bone volume and quality. Most importantly, asymmetrical, and overall degeneration of facet joints was strongly correlated to intervertebral axial rotation. Additionally, kyphotic intervertebral segments in the sagittal plane were good predictors of increased facet joint degeneration and back pain. CONCLUSION: Facet joint degeneration is associated with axial deformity, kyphotic intervertebral angle and back pain intensity in AIS. These results suggest that facet joints are important features to consider for rotational instability in AIS spines and related disease progression and perceived back pain.

[Early mortality and risk analysis in adult patients with maintenance hemodialysis].

Objective: To retrospectively analyze the early mortality and related risk factors in adult patients with maintenance hemodialysis (MHD). Methods: Adult MHD patients from 2008 to 2018 were enrolled and divided into training data group and validation data group. In training data group, multivariate logistic regression was used to analyze the risk factors of early death within 120 days after hemodialysis and establish a prediction model. The receiver operating characteristic (ROC) curve was applied to evaluate the prediction ability of the model. Results: A total of 4 885 patients were included. The cumulative mortality within 120 days was 20.97/100 person years, and that within 365 days was 12.25/100 person years. A total of 3 603 patients in the training data group were analyzed. The following risk factors were correlated with early mortality (all P<0.05), including age at start of dialysis over 60 years old (OR=1.792), non-chronic glomerulonephritis (OR=2.214), cardio-cerebrovascular disease (OR=2.695), plasma albumin less than 35 g/L (OR=1.358), platelet count less than 120×109/L (OR=2.194), serum creatinine less than 600 µmol/L (OR=1.652), blood urea nitrogen over 30 mmol/L (OR=1.887), blood phosphorus less than 1.13 mmol/L (OR=1.783), pulse pressure over 55 mmHg(1 mmHg=0.133 kPa) (OR=1.656), low density lipoprotein less than 1.5 mmol/L (OR=1.873), and blood calcium over 2.5 mmol/L (OR=1.876). Risk prediction model was established. The other 1 282 cases in the validation data group were verified. The area under ROC curve was 0.810, with sensitivity 85.7%, and specificity 62.5%. Conclusion: The mortality rate of adult MHD patients within 120 days after dialysis is high. The established prediction model can effectively predict the risk of early death.

To treat or not to treat? An evidence-based practice guide for the management of endometrial polyps.

Endometrial polyps are a common finding, with a prevalence of about 40%, and are usually diagnosed incidentally as most are asymptomatic. Symptomatic polyps usually present with abnormal uterine bleeding and/or sub-fertility. About 25% of polyps resolve spontaneously if managed conservatively. The usual management of endometrial polyps, symptomatic or asymptomatic, is polypectomy, performed primarily to exclude malignancy within the polyp despite the overall risk of malignancy being low (about 3%). The main risk factors for malignancy are menopause and abnormal uterine bleeding, with hypertension, obesity, diabetes mellitus, and tamoxifen use thought to play a lesser role. Transvaginal ultrasonography is the primary diagnostic tool for endometrial polyps although visualization by hysteroscopy is the gold standard for diagnosis. There is no proven preventative or medical treatment, with complete polyp removal under hysteroscopic guidance the recommended surgical treatment. Some women may decline surgical endometrial polyp management due to the small inherent risks. Conservative management is an option for asymptomatic premenopausal and postmenopausal women, whilst polypectomy is recommended for all women with abnormal uterine bleeding. Management should be individualized and made in consultation with the patient.

Comparative efficacy and safety of lock solutions for the prevention of catheter-related complications including infectious and bleeding events in adult haemodialysis patients: a systematic review and network meta-analysis.

BACKGROUND: Central venous catheters are used extensively as temporary or permanent vascular access for haemodialysis patients. Catheter-related bloodstream infections are the main complication of central venous catheters and increase morbidity and mortality in haemodialysis patients. OBJECTIVES: The aim was to assess the most appropriate lock solution for central venous catheters to prevent catheter-related bloodstream infections and other complications. DATA SOURCES: Medline, Embase and the Cochrane Central Register of Controlled Trials from the date of their inception to August 2018 were used as data sources. The reference lists of eligible studies and relevant reviews were also checked. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: Randomized controlled trials (RCTs) comparing different lock solutions for the prevention of central venous catheter-related infectious and bleeding complications for adult dialysis patients were included. INTERVENTIONS: Interventions were lock solutions for haemodialysis catheters. METHODS: The primary outcomes were catheter-related bloodstream infections and bleeding events. The secondary outcomes were catheter malfunction, exit-site infection, and all-cause mortality. We estimated summary risk ratios (RRs) using pairwise and network meta-analysis. We assessed the risk of bias of individual studies with the Cochrane risk of bias tool. RESULTS: Forty-nine trials (7020 patients) were included for this study. Compared with heparin 5000 U/mL, antibiotic locks (antibiotics with trisodium citrate (TSC), ethylenediamine tetraacetic acid (EDTA), heparin 5000 U/mL, low-dose heparin or urokinase) and ethanol locks were more effective in preventing catheter-related bloodstream infections. Antimicrobial agents plus low-dose heparin (500-2500 U/mL), TSC and low-dose heparin locks had lower risk of bleeding events than heparin 5000 U/mL. None of the lock solutions reduced rates of catheter malfunction and all-cause mortality compared with heparin 5000 U/mL. In summary, antibiotics plus low-dose heparin was ranked as the best lock solution. The overall results were not materially changed in sensitivity analyses. CONCLUSIONS: Taking into account both efficacy and safety, antibiotics plus low-dose heparin (500-2500 U/mL) may be the preferred lock solution.

Efficacy of Phacoemulsification Alone vs Phacoemulsification With Goniosynechialysis in Patients With Primary Angle-Closure Disease: A Randomized Clinical Trial.

IMPORTANCE: The effectiveness of intraocular pressure (IOP) lowering phacoemulsification combined with goniosynechialysis (GSL) compared with phacoemulsification without GSL remains unknown. OBJECTIVE: To compare the IOP outcome after 1 year in patients with synechial primary angle-closure disease (PACD) and cataract who underwent phacoemulsification with intraocular lens implantation (PEI) alone compared with PEI with GSL (PEI-GSL). DESIGN, SETTING, AND PARTICIPANTS: A multicenter randomized clinical trial was conducted from September 29, 2011, to March 16, 2015; data analysis was performed from April 1, 2015, to March 4, 2019. Patients with PACD, defined as primary angle closure or primary angle-closure glaucoma, and at least 90° peripheral anterior synechiae (PAS) with cataract were included. Patients were randomized to undergo PEI alone or PEI-GSL. Patients were followed up for 1 year with standardized evaluations. Intention-to-treat analysis was performed. INTERVENTIONS: Phacoemulsification with intraocular lens implantation alone or with GSL. MAIN OUTCOMES AND MEASURES: Successful control of IOP at 12 months, defined as IOP 21 mm Hg or lower without use of topical IOP-lowering medications and a decrease in IOP of 20% or more from baseline IOP. RESULTS: Data from 78 patients (78 eyes) were analyzed. Of these, 37 patients were Chinese (47.4%) and 54 were women (69.2%); mean (SD) age was 67.7 (8.9) years. Mean deviation (SD) at baseline was -13.5 dB (9.4 dB). Forty patients were randomized to the PEI group and 38 to the PEI-GSL group. The mean (SD) IOP at baseline was 22.3 (8.5) mm Hg for the PEI group and 22.9 (5.3) mm Hg for the PEI-GSL group. At 1 year, the mean IOP was 14.3 (5.0) mm Hg for the PEI group and 15.9 (4.5) mm Hg for the PEI-GSL group. Successful control at 1 year occurred in 21 patients (52.5%) in the PEI group and 22 patients (57.9%) in the PEI-GSL group (mean difference, 5.4%; 95% CI, -18.0% to 28.2%; P = .63). In eyes that achieved successful control, mean IOP at 1 year was 12.5 (2.7) mm Hg (range, 7.0-19.0) for the PEI group and 13.6 (2.4) mm Hg (range, 9.0-18.0) for the PEI-GSL group. The number of medications at baseline and 1 year decreased from a mean of 2.2 (0.8) to 0.5 (0.9) in the PEI group and 1.9 (0.9) to 0.6 (1.2) in the PEI-GSL group (P < .001 for each), with a mean change difference of 0.4% (95% CI, -0.02% to 0.9%; P = .06). There were 3 postoperative complications (7.5%) in the PEI group and 3 (7.9%) in the PEI-GSL group. These included IOP spike (IOP≥30 mm Hg) (n = 3), excessive anterior chamber inflammation (n = 1), and posterior capsule opacification (n = 2). CONCLUSIONS AND RELEVANCE: This randomized clinical trial was unable to show that PEI-GSL added additional IOP lowering compared with PEI alone in patients with PACD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02376725.

Noncanonical functions of microRNA pathway enzymes - Drosha, DGCR8, Dicer and Ago proteins.

MicroRNAs (miRNAs) are small regulatory noncoding RNAs that are generated in the canonical RNA interference (RNAi) pathway. Drosha, DiGeorge syndrome critical region 8 (DGCR8) and Dicer are key players in miRNA biogenesis. Argonaute (Ago) proteins bind to miRNAs and are guided by them to find messenger RNA targets and carry out post-transcriptional silencing of protein-coding genes. Recently, emerging evidence suggests that RNAi factors have a range of noncanonical functions that are beyond miRNA biogenesis. These functions pertain to various biological processes, such as development, transcriptional regulation, RNA processing and maintenance of genome integrity. Here, we review recent literature reporting miRNA-independent, noncanonical functions of Drosha, DGCR8, Dicer and Ago proteins and discuss the importance of these functions.

Morphological and molecular evidence for two new species in Lepiota from China.

Two new species in Lepiota sect. Ovisporae are described from tropical China. Lepiota angusticystidiata has a pileus with brownish yellow squamules covering a trichodermial palisade, ellipsoidal basidiospores, and narrowly clavate cheilocystidia; L. brunneosquamulosa has a tomentose, squamulose pileus with brownish yellow to yellowish brown concentric zones covering a trichodermial palisade, rarely with short elements, ellipsoidal or subcylindrical basidiospores with straight adaxial side, and no cheilocystidia. Phylogenetic relationships among species of sect. Ovisporae were inferred based on DNA sequences of the internal transcribed spacer region (ITS1-5.8S-ITS2 = ITS), the 5' end of the 28S gene (D1-D2-D3 variable domains), and partial sequences of the intergenic spacer (IGS1) of the nuc rDNA and the mitochondrial small ribosomal RNA gene (mtSSU), supporting the delineation of these new species.

Perceptual and Motor Performance of Combat-Sport Athletes Differs According to Specific Demands of the Discipline.

The specific demands of a combat-sport discipline may be reflected in the perceptual-motor performance of its athletes. Taekwondo, which emphasizes kicking, might require faster perceptual processing to compensate for longer latencies to initiate lower-limb movements and to give rapid visual feedback for dynamic postural control, while Karate, which emphasizes both striking with the hands and kicking, might require exceptional eye-hand coordination and fast perceptual processing. In samples of 38 Taekwondo athletes (16 females, 22 males; mean age = 19.9 years, SD = 1.2), 24 Karate athletes (9 females, 15 males; mean age = 18.9 years, SD = 0.9), and 35 Nonathletes (20 females, 15 males; mean age = 20.6 years, SD = 1.5), we measured eye-hand coordination with the Finger-Nose-Finger task, and both perceptual-processing speed and attentional control with the Covert Orienting of Visual Attention (COVAT) task. Eye-hand coordination was significantly better for Karate athletes than for Taekwondo athletes and Nonathletes, but reaction times for the upper extremities in the COVAT task-indicative of perceptual-processing speed-were faster for Taekwondo athletes than for Karate athletes and Nonathletes. In addition, we found no significant difference among groups in attentional control, as indexed by the reaction-time cost of an invalid cue in the COVAT task. The results suggest that athletes in different combat sports exhibit distinct profiles of perceptual-motor performance.

Identifying the biomarkers of multiple sclerosis based on non-coding RNA signature.

OBJECTIVE: miRNAs are key regulators in multiple sclerosis. To gain a better understanding of the molecular mechanisms of multiple sclerosis, differentially expressed microRNAs (DE-miRNAs) and genes (DEGs) were analyzed. MATERIALS AND METHODS: The miRNA expression profile GSE43590 including 11 samples of peripheral blood T-cells from relapsing-remitting MS patients and 9 normal samples as well as gene expression profile GSE52139 including 8 periplaque samples and 8 normal samples were downloaded from Gene Expression Omnibus. Then, DE-miRNAs and DEGs were identified using limma. Moreover, the target genes of DE-miRNAs were screened. Additionally, the integrated regulatory network of DEGs, DE-miRNAs and targets was constructed using Cytoscape. What's more, the functional modules were also screened using MINE in Cytoscape. Lastly, the functional annotation of genes in modules was conducted using DAVID. RESULTS: A total of 2394 DEGs were screened in 8 periplaque samples. Additionally, 296 DE-miRNAs were identified in the 11 samples of peripheral blood T-cells from relapsing-remitting MS patients. Besides, 6 functional modules (A-F) were screened. Among them, has-miR-197 could target HNF4A. What's more, HNF4A could interact with CYP3A4. Additionally, has-miR-125b could target ID1 and ID3. Besides, ID1 could interact with THBS1. Furthermore, functional enrichment showed that CYP3A4 was significantly related to vitamin metabolic process. For the pathway enrichment, ID1 and ID3 were significantly enriched in TGF-beta signaling pathway. CONCLUSIONS: Some important DE-miRNAs (such as has-miR-197and has-miR-125b) might be crucial for MS by regulating the expressions of their target genes.

A GPU based high-resolution multilevel biomechanical head and neck model for validating deformable image registration.

PURPOSE: Validating the usage of deformable image registration (dir) for daily patient positioning is critical for adaptive radiotherapy (RT) applications pertaining to head and neck (HN) radiotherapy. The authors present a methodology for generating biomechanically realistic ground-truth data for validating dir algorithms for HN anatomy by (a) developing a high-resolution deformable biomechanical HN model from a planning CT, (b) simulating deformations for a range of interfraction posture changes and physiological regression, and (c) generating subsequent CT images representing the deformed anatomy. METHODS: The biomechanical model was developed using HN kVCT datasets and the corresponding structure contours. The voxels inside a given 3D contour boundary were clustered using a graphics processing unit (GPU) based algorithm that accounted for inconsistencies and gaps in the boundary to form a volumetric structure. While the bony anatomy was modeled as rigid body, the muscle and soft tissue structures were modeled as mass-spring-damper models with elastic material properties that corresponded to the underlying contoured anatomies. Within a given muscle structure, the voxels were classified using a uniform grid and a normalized mass was assigned to each voxel based on its Hounsfield number. The soft tissue deformation for a given skeletal actuation was performed using an implicit Euler integration with each iteration split into two substeps: one for the muscle structures and the other for the remaining soft tissues. Posture changes were simulated by articulating the skeletal structure and enabling the soft structures to deform accordingly. Physiological changes representing tumor regression were simulated by reducing the target volume and enabling the surrounding soft structures to deform accordingly. Finally, the authors also discuss a new approach to generate kVCT images representing the deformed anatomy that accounts for gaps and antialiasing artifacts that may be caused by the biomechanical deformation process. Accuracy and stability of the model response were validated using ground-truth simulations representing soft tissue behavior under local and global deformations. Numerical accuracy of the HN deformations was analyzed by applying nonrigid skeletal transformations acquired from interfraction kVCT images to the model's skeletal structures and comparing the subsequent soft tissue deformations of the model with the clinical anatomy. RESULTS: The GPU based framework enabled the model deformation to be performed at 60 frames/s, facilitating simulations of posture changes and physiological regressions at interactive speeds. The soft tissue response was accurate with a R(2) value of >0.98 when compared to ground-truth global and local force deformation analysis. The deformation of the HN anatomy by the model agreed with the clinically observed deformations with an average correlation coefficient of 0.956. For a clinically relevant range of posture and physiological changes, the model deformations stabilized with an uncertainty of less than 0.01 mm. CONCLUSIONS: Documenting dose delivery for HN radiotherapy is essential accounting for posture and physiological changes. The biomechanical model discussed in this paper was able to deform in real-time, allowing interactive simulations and visualization of such changes. The model would allow patient specific validations of the dir method and has the potential to be a significant aid in adaptive radiotherapy techniques.

Feasibility of automated pancreas segmentation based on dynamic MRI.

OBJECTIVE: MRI-guided radiotherapy is particularly attractive for abdominal targets with low CT contrast. To fully utilize this modality for pancreas tracking, automated segmentation tools are needed. A hybrid gradient, region growth and shape constraint (hGReS) method to segment two-dimensional (2D) upper abdominal dynamic MRI (dMRI) is developed for this purpose. METHODS: 2D coronal dynamic MR images of two healthy volunteers were acquired with a frame rate of 5 frames per second. The regions of interest (ROIs) included the liver, pancreas and stomach. The first frame was used as the source where the centres of the ROIs were manually annotated. These centre locations were propagated to the next dMRI frame. Four-neighborhood region transfer growth was performed from these initial seeds before refinement using shape constraints. RESULTS from hGReS and two other automated segmentation methods using integrated edge detection and region growth (IER) and level set, respectively, were compared with manual contours using Dice's index (DI). RESULTS: For the first patient, the hGReS resulted in the organ segmentation accuracy as a measure by the DI (0.77) for the pancreas, superior to the level set method (0.72) and IER (0.71). The hGReS was shown to be reproducible on the second subject, achieving a DI of 0.82, 0.92 and 0.93 for the pancreas, stomach and liver, respectively. Motion trajectories derived from the hGReS were highly correlated to respiratory motion. CONCLUSION: We have shown the feasibility of automated segmentation of the pancreas anatomy on dMRI. ADVANCES IN KNOWLEDGE: Using the hybrid method improves segmentation robustness of low-contrast images.

A nonvoxel-based dose convolution/superposition algorithm optimized for scalable GPU architectures.

PURPOSE: Real-time adaptive planning and treatment has been infeasible due in part to its high computational complexity. There have been many recent efforts to utilize graphics processing units (GPUs) to accelerate the computational performance and dose accuracy in radiation therapy. Data structure and memory access patterns are the key GPU factors that determine the computational performance and accuracy. In this paper, the authors present a nonvoxel-based (NVB) approach to maximize computational and memory access efficiency and throughput on the GPU. METHODS: The proposed algorithm employs a ray-tracing mechanism to restructure the 3D data sets computed from the CT anatomy into a nonvoxel-based framework. In a process that takes only a few milliseconds of computing time, the algorithm restructured the data sets by ray-tracing through precalculated CT volumes to realign the coordinate system along the convolution direction, as defined by zenithal and azimuthal angles. During the ray-tracing step, the data were resampled according to radial sampling and parallel ray-spacing parameters making the algorithm independent of the original CT resolution. The nonvoxel-based algorithm presented in this paper also demonstrated a trade-off in computational performance and dose accuracy for different coordinate system configurations. In order to find the best balance between the computed speedup and the accuracy, the authors employed an exhaustive parameter search on all sampling parameters that defined the coordinate system configuration: zenithal, azimuthal, and radial sampling of the convolution algorithm, as well as the parallel ray spacing during ray tracing. The angular sampling parameters were varied between 4 and 48 discrete angles, while both radial sampling and parallel ray spacing were varied from 0.5 to 10 mm. The gamma distribution analysis method (γ) was used to compare the dose distributions using 2% and 2 mm dose difference and distance-to-agreement criteria, respectively. Accuracy was investigated using three distinct phantoms with varied geometries and heterogeneities and on a series of 14 segmented lung CT data sets. Performance gains were calculated using three 256 mm cube homogenous water phantoms, with isotropic voxel dimensions of 1, 2, and 4 mm. RESULTS: The nonvoxel-based GPU algorithm was independent of the data size and provided significant computational gains over the CPU algorithm for large CT data sizes. The parameter search analysis also showed that the ray combination of 8 zenithal and 8 azimuthal angles along with 1 mm radial sampling and 2 mm parallel ray spacing maintained dose accuracy with greater than 99% of voxels passing the γ test. Combining the acceleration obtained from GPU parallelization with the sampling optimization, the authors achieved a total performance improvement factor of >175 000 when compared to our voxel-based ground truth CPU benchmark and a factor of 20 compared with a voxel-based GPU dose convolution method. CONCLUSIONS: The nonvoxel-based convolution method yielded substantial performance improvements over a generic GPU implementation, while maintaining accuracy as compared to a CPU computed ground truth dose distribution. Such an algorithm can be a key contribution toward developing tools for adaptive radiation therapy systems.

High risk for obesity in children with a subtype of developmental coordination disorder.

The purpose of this study was to compare the prevalence of overweight and obesity in typically developing (TD) children, children with developmental coordination disorder (DCD) and balance problems (DCD-BP), and children with DCD without balance problems (DCD-NBP). Two thousand and fifty-seven children (1095 boys, 962 girls) ages 9-12 years were recruited from 18 elementary schools in Taiwan. The Movement Assessment Battery for Children was used to assess motor coordination ability. International cut-off points for body mass index were used to classify participants into the following groups: normal-weight, overweight or obese. Compared with TD children, children in the DCD-BP group were more than twice as likely to be obese (OR=2.28; 95% CI=1.41-3.68). DCD-BP children were also more likely to be obese compared to DCD-NBP children (OR=1.79; 95% CI=1.02-3.16). Boys in the DCD-BP group were more likely to be obese when compared to DCD-BP girls (OR=3.12; 95% CI=1.28-7.57). Similarly, DCD-NBP boys were more likely to be obese when compared to DCD-NBP girls (OR=2.67; 95% CI=1.21-5.89). Children with both DCD and BP were significantly more likely to be obese when compared to TD and DCD-NBP children. From an intervention perspective, the inclusion of regular physical activity, including activities that encourage development of both balance and energy expenditure, may be required to prevent obesity in this population.

Valosin-containing protein regulates the proteasome-mediated degradation of DNA-PKcs in glioma cells.

DNA-dependent protein kinase (DNA-PK) has an important role in the repair of DNA damage and regulates the radiation sensitivity of glioblastoma cells. The VCP (valosine-containing protein), a chaperone protein that regulates ubiquitin-dependent protein degradation, is phosphorylated by DNA-PK and recruited to DNA double-strand break sites to regulate DNA damage repair. However, it is not clear whether VCP is involved in DNA-PKcs (DNA-PK catalytic subunit) degradation or whether it regulates the radiosensitivity of glioblastoma. Our data demonstrated that DNA-PKcs was ubiquitinated and bound to VCP. VCP knockdown resulted in the accumulation of the DNA-PKcs protein in glioblastoma cells, and the proteasome inhibitor MG132 synergised this increase. As expected, this increase promoted the efficiency of DNA repair in several glioblastoma cell lines; in turn, this enhanced activity decreased the radiation sensitivity and prolonged the survival fraction of glioblastoma cells in vitro. Moreover, the VCP knockdown in glioblastoma cells reduced the survival time of the xenografted mice with radiation treatment relative to the control xenografted glioblastoma mice. In addition, the VCP protein was also downregulated in ~25% of GBM tissues from patients (WHO, grade IV astrocytoma), and the VCP protein level was correlated with patient survival (R(2)=0.5222, P<0.05). These findings demonstrated that VCP regulates DNA-PKcs degradation and increases the sensitivity of GBM cells to radiation.

Deficits in the covert orienting of attention in children with Developmental Coordination Disorder: does severity of DCD count?

Children with Developmental Coordination Disorder (DCD) show deficits in the covert orienting of visuospatial attention, suggesting an underlying issue in attentional disengagement and/or inhibitory control. However, an important theoretical issue that remains unclear is whether the pattern of deficits varies with DCD severity. Fifty-one children with moderate DCD (MDCD), 24 children with severe DCD (SDCD), and 38 typically developing (TD) children participated in the study. Their performance was compared on the covert orienting of visuospatial attention task (COVAT), specifically the voluntary control mode. Results showed that the pattern of performance differed between groups. At a short stimulus-response asynchrony (350 ms), the difference in response times for validly and invalidly cued trials was similar for all three groups. However, at the longer SOA (800 ms), both DCD groups continued to show a relative disadvantage for responses that followed invalid cues. This suggests that a deficit in response inhibition and/or attentional disengagement is manifest in children with both moderate and severe DCD. The implications of these findings for theory and treatment are discussed.

SU-E-T-608: Integrated Beam Orientation and Fluence Map Optimization in Radiation Therapy Treatment Planning.

PURPOSE: To efficiently select high-quality coplanar or non-coplanar beam orientations for IMRT treatments while formally and explicitly incorporating the effect of the selected beam orientations on the quality of the dose distribution obtained by the treatment plan optimization model. METHODS: Beam orientation models consider a discrete set of potential coplanar and/or non-coplanar beam locations around the patient. A new greedy algorithm is proposed to solve a model that integrates beam orientation optimization (BOO) and fluence map optimization (FMO). The algorithm iteratively adds beams to a FMO model. In each iteration, an attractiveness measure is associated with each remaining candidate beam orientation. This attractiveness measure is based explicitly on an optimal dose distribution that allows only the currently selected set of beams to be used. Several alternate attractiveness measures are considered which use either first-order information or both first and second-order information. Performance of the algorithm was assessed on a clinical lung cancer case. RESULTS: The developed beam selection algorithm was applied to a lung cancer case using either coplanar beams or both coplanar and non-coplanar beams. In the coplanar case, beam orientations were found that produce a superior dose distribution to that using an equal number of equi-spaced beams. In the non-coplanar case it was found that fewer beams were needed to produce a dose distribution of comparable quality to that found in the coplanar case. CONCLUSIONS: The developed solution approach showcases the potential benefits of integrating different steps in the treatment plan optimization process. By integrating the BOO and FMO models, treatment plan quality was explicitly incorporated into the beam selection process. BOO can be automated and implemented efficiently, which eliminates the guesswork involved in manually adjusting beam orientations in IMRT treatment planning.

SU-D-211-02: A Framework for 4pi Radiotherapy.

PURPOSE: Inclusion of highly non-coplanar treatment angles increases radiations dose conformality and critical organ sparing. However, implementation of this treatment strategy has been hampered by inaccurate solution space modeling, limited automated beam selection methods, the lack of efficient beam sequencing program and integrated collision prevention. The aim is to develop a 4pi radiotherapy paradigm that takes full advantage of modern computer-controlled robotic C-arm linear accelerators. METHODS: The beam geometry solution space was modeled by 3D surface scanning of the couch, gantry and patient. In order to utilize the entire solution space and optimize MLC resolution, variable source-to-tumor distances were introduced. Conformai radiation doses were computed using convolution/superposition from uniformly distributed solid angles. Beam orientation optimization was performed using a column generation and pricing approach, which was also used to optimize beam fluence intensity modulation. A level set method was then employed to automatically sequence beams so the treatment time and couch motion can be minimized while avoiding collision on the path. RESULTS: The machine and patient surface was accurately measured and a cocoon shaped solution space was created with an integrated gap buffer of 4 cm. 14 conformai beams were typically selected to maximize target dose coverage and minimize critical organ doses. Compared with manual non-coplanar and coplanar volumetric modulated arc therapy plans, an average 20% improvement was observed in high dose spillage, defined as the 50% isodose volume divided by the target volume, in a wide range of clinical cases including brain, lung, liver and partial breast cancer. CONCLUSIONS: We have established a framework that overcomes major technical difficulties associated with automated planning and delivery of highly non-coplanar treatment on the widely available C-arm linacs. Compared with coplanar volumetric modulated arc therapy plans, 4pi plans improve nearly all aspects of the dosimetry while remain highly deliverable.

SU-D-BRB-05: Small Animal Lung Compliance Imaging: Assessment System for Tissue Sensitivity to Radiation Induced Lung Injury.

PURPOSE: Recent clinical trials and animal studies have indicated that the tissue sensitivity to radiation induced lung injury (RILI) may be region- specific. In this study, we propose a new 4D cone beam CT (CBCT) basedcompliance imaging method to measure regional pulmonary function change in precisely irradiated small animal under CBCT guidance on small animal radiation research platform (SARRP) to facilitate our understanding of region-specific tissue sensitivity to RILI. METHODS: Four Sprague-Dawley rats underwent prospective pressure gated 4D CBCT on SARRP. Three animals were selected as control group which underwent a second 4D CBCT scan. The fourth animal was irradiated in the central lung (24 Gy) using 3 × 3 mm collimating cone 2 months prior to the scan. The specific compliance (Csp) was calculated via the real time pressure measurement from the ventilator and displacement field from 3D B-spline image registration between the end of inhale and end of exhale phases from the 4D CBCT scan. The 3D Csp maps from the control animal group were mapped to the irradiated animal as a Csp functional atlas for statistical analysis. We alsoevaluated the repeatability of the Csp measurement on a voxel-by-voxel basis. RESULTS: No significant Csp difference is found after two month of radiation between the irradiated rat (0.22±0.05) and the functional atlas (0.21±0.07). The observation is consistent with previous publications. The averaged linear correlation coefficient between the voxel-by-voxel Csp measurements from initial and repeat scans in control group is 0.98. CONCLUSIONS: We proposed a method that uses 4D CBCT based compliance imaging to measure region-specific tissue sensitivity of RILI. We compared the irradiated animal two months after radiation with the control group. Our study shows an excellent robustness of the proposed method for regional lung tissue specific compliance measurement. This work was supported in part by UVa George Amorino Pilot Grant.