Do lycra garments improve function and movement in children with cerebral palsy?

The mother of a 5-year-old boy with athetoid cerebral palsy complains of difficulties putting his Lycra suit on each day. She is keen to know if it actually helps improve his function and movement. STRUCTURED CLINICAL QUESTION In children with cerebral palsy (population), do Lycra garments (intervention) improve function and posture (outcome)? SEARCH STRATEGY The search was performed in October 2009

Cognitive Function of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate

BACKGROUND: SPD489-404 was the first 2-year safety study of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. In accordance with advice from the European Medicines Agency, assessment of cognitive function was a predefined safety outcome in SPD489-404. OBJECTIVE: The objective of this study was to assess cognitive function over 2 years in study SPD489-404, using the Cambridge Neuropsychological Test Automated Battery (CANTAB). METHODS: Participants aged 6-17 years received dose-optimised open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) for 104 weeks. Cognition was assessed using four CANTAB tasks; Delayed Matching to Sample (DMS), Spatial Working Memory (SWM), Stop Signal Task (SST) and Reaction Time (RTI). Key and additional variables were pre-specified for each CANTAB task; groupwise mean percentage changes in key variables from baseline of > 5% were considered potentially clinically significant. RESULTS: All 314 enrolled participants received lisdexamfetamine dimesylate and were included in the safety population, and 191 (60.8%) completed the study. No potentially clinically significant deteriorations from baseline were observed in any key CANTAB variable over the 2 years of the study. Based on predefined thresholds, potentially clinically significant improvements from baseline were observed at 6 months (DMS median reaction time, mean per cent change, - 6.6%; SWM total between-search errors, - 22.8%; SST stop signal reaction time, -18.9%), and at the last on-treatment assessment (DMS median reaction time, - 6.5%; SWM total between-search errors, - 32.6%; SST stop signal reaction time, - 25.7%). CONCLUSIONS: Lisdexamfetamine dimesylate treatment for 2 years was not associated with deterioration of cognitive function in children and adolescents with attention-deficit/hyperactivity disorder. Although improvements in some cognitive measures were observed, lack of a control group makes interpretation of the findings difficult. Further studies of the impact of stimulants on cognition are required

Qualitative kinematics of planar robots: Intelligent connection

AbstractThis paper proposes a qualitative representation for robot kinematics in order to close the gap, raised by the perception–action problem, with a focus on intelligent connection of qualitative states to their corresponding numeric data in a robotic system. First, qualitative geometric primitives are introduced by combining a qualitative orientation component and qualitative translation component using normalisation techniques. A position in Cartesian space can be mathematically described by the scalable primitives. Secondly, qualitative robot kinematics of an n-link planar robot is derived in terms of the qualitative geometry primitives. Finally, it shows how to connect quantitativeness and qualitativeness of a robotic system. On the one hand, the integration of normalisation and domain knowledge generates normalised labels to introduce the meaningful parameters into the proposed representation. On the other hand, the normalised labels of this representation can be converted to a quantitative description using aggregation operators, whose numeric outputs can be used to generate desired trajectories based on mature interpolation techniques

“OASIS-F”: development of a fuzzy online assessment system

A web-based tutorial and examination system has been developed in the Department of Electrical and Electronic Engineering at The University of Auckland. OASIS is an Online ASsessment and Information System. OASIS comprises an extensive question database and server-side program that delivers questions to students, marks their responses and records students’ activities and performance. In OASIS skills are developed by solving practical problems, which are all marked to give instant feedback. The students can practice on these problems from any web browser at any location on or off campus. Using OASIS does not require any special application software since all of the processing is done on the web server. Since 2000 the emphasis has been on giving students core-competency and skills but in a further development of OASIS a ‘fuzzy’ marking scheme is being introduced to allow marking of ‘softer’ subject material where ‘crisp’ numerical answers are inappropriate. Thus it will be possible to assess a student’s ‘understanding’ of some topic. OASIS-fuzzy allows a consistent marking scheme for these situations by assessing the student’s ability to ‘see the wood for the trees’. In OASIS-fuzzy the system measures what is in effect the ‘centre of gravity’ of the student’s knowledge on a particular topic by assessing their ability to rank information about that topic in order of importance. This we believe to be a measure of their ‘understanding’ of the topic. This paper presents a brief description of the system, its structure and its features

Functional outcomes from a head-to-head, randomized, double-blind trial of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder and an inadequate response to methylphenidate

Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in multiple domains of patients' lives. A secondary objective of this randomized, active-controlled, head-to-head, double-blind, dose-optimized clinical trial was to compare the effects of lisdexamfetamine dimesylate (LDX) and atomoxetine (ATX) on functional impairment in children and adolescents with ADHD. Patients aged 6-17 years with an ADHD Rating Scale IV total score ≥ 28 and an inadequate response to methylphenidate treatment (judged by investigators) were randomized (1:1) to once-daily LDX or ATX for 9 weeks. Parents/guardians completed the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at baseline and at week 9 or early termination. p values were nominal and not corrected for multiple comparisons. Of 267 randomized patients, 200 completed the study (LDX 99, ATX 101). At baseline, mean WFIRS-P total score in the LDX group was 0.95 [standard deviation (SD) 0.474; 95% confidence interval (CI) 0.87, 1.03] and in the ATX group was 0.91 (0.513; 0.82, 1.00). Scores in all WFIRS-P domains improved from baseline to endpoint in both groups, with least-squares mean changes in total score of -0.35 (95% CI -0.42, -0.29) for LDX and -0.27 (-0.33, -0.20) for ATX. The difference between LDX and ATX was statistically significant (p < 0.05) for the Learning and School (effect size of LDX vs ATX, 0.43) and Social Activities (0.34) domains and for total score (0.27). Both treatments reduced functional impairment in children and adolescents with ADHD; LDX was statistically significantly more effective than ATX in two of six domains and in total score

Resilience and return-to-work pain interventions:systematic review

Background:- Resilience is a developing concept in relation to pain, but has not yet been reviewed in return-to-work (RTW) contexts. Aims:- To explore the role of resilience enhancement in promoting work participation for chronic pain sufferers, by reviewing the effectiveness of existing interventions. Methods:- Resilience was operationalized as: self-efficacy, active coping, positive affect, positive growth, positive reinforcement, optimism, purpose in life and acceptance. Five databases were searched for randomized controlled trials (RCTs) whose interventions included an element of resilience designed to help RTW/staying at work for chronic pain sufferers. Study appraisal comprised the Cochrane risk of bias (RoB) tool and additional quality assessment. Findings were synthesized narratively and between-group differences of outcomes were reported. Heterogeneous PICO (population, intervention, comparator, outcome) elements precluded meta-analysis. Results:- Thirty-four papers from 24 RCTs were included. Interventions varied; most were multidisciplinary, combining behavioural, physical and psychological pain management and vocational rehabilitation. Four found RTW/staying at work improved with intensive multidisciplinary interventions compared with less intensive, or no, treatment. Of these, one had low RoB; three scored poorly on allocation concealment and selective outcome reporting. Four trials had mixed results, e.g. interventions enabling reduced sick leave for people on short-term not long-term leave; 16 showed no improvement. Five trials reported resilience outcomes were improved by interventions but these were not always trials in which RTW improved. Conclusions:- Effectiveness of resilience interventions for chronic pain sufferers on RTW is uncertain and not as helpful as anticipated. Further agreement on its conceptualization and terminology and that of RTW is needed

Analysis of wheat SAGE tags reveals evidence for widespread antisense transcription

BACKGROUND: Serial Analysis of Gene Expression (SAGE) is a powerful tool for genome-wide transcription studies. Unlike microarrays, it has the ability to detect novel forms of RNA such as alternatively spliced and antisense transcripts, without the need for prior knowledge of their existence. One limitation of using SAGE on an organism with a complex genome and lacking detailed sequence information, such as the hexaploid bread wheat Triticum aestivum, is accurate annotation of the tags generated. Without accurate annotation it is impossible to fully understand the dynamic processes involved in such complex polyploid organisms. Hence we have developed and utilised novel procedures to characterise, in detail, SAGE tags generated from the whole grain transcriptome of hexaploid wheat. RESULTS: Examination of 71,930 Long SAGE tags generated from six libraries derived from two wheat genotypes grown under two different conditions suggested that SAGE is a reliable and reproducible technique for use in studying the hexaploid wheat transcriptome. However, our results also showed that in poorly annotated and/or poorly sequenced genomes, such as hexaploid wheat, considerably more information can be extracted from SAGE data by carrying out a systematic analysis of both perfect and "fuzzy" (partially matched) tags. This detailed analysis of the SAGE data shows first that while there is evidence of alternative polyadenylation this appears to occur exclusively within the 3' untranslated regions. Secondly, we found no strong evidence for widespread alternative splicing in the developing wheat grain transcriptome. However, analysis of our SAGE data shows that antisense transcripts are probably widespread within the transcriptome and appear to be derived from numerous locations within the genome. Examination of antisense transcripts showing sequence similarity to the Puroindoline a and Puroindoline b genes suggests that such antisense transcripts might have a role in the regulation of gene expression. CONCLUSION: Our results indicate that the detailed analysis of transcriptome data, such as SAGE tags, is essential to understand fully the factors that regulate gene expression and that such analysis of the wheat grain transcriptome reveals that antisense transcripts maybe widespread and hence probably play a significant role in the regulation of gene expression during grain development

Hinge Region in DNA Packaging Terminase pUL15 of Herpes Simplex Virus: A Potential Allosteric Target for Antiviral Drugs

Approximately 80% of adults are infected with a member of the herpesviridae family. Herpesviruses establish life-long latent infections within neurons, which may reactivate into lytic infections due to stress or immune suppression. There are nine human herpesviruses (HHV) posing health concerns from benign conditions to life threatening encephalitis, including cancers associated with viral infections. The current treatment options for most HHV conditions mainly include several nucleoside and nucleotide analogs targeting viral DNA polymerase. Although these drugs help manage infections, their common mechanism of action may lead to the development of drug resistance, which is particularly devastating in immunocompromised patients. Therefore, new classes of drugs directed against novel targets in HHVs are necessary to alleviate this issue. We analyzed the conservation rates of all proteins in herpes simplex virus 1 (HHV-1), a representative of the HHV family and one of the most common viruses infecting the human population. Furthermore, we generated a full-length structure model of the most conserved HHV-1 protein, the DNA packaging terminase pUL15. A series of computational analyses were performed on the model to identify ATP and DNA binding sites and characterize the dynamics of the protein. Our study indicates that proteins involved in HHV-1 DNA packaging and cleavage are amongst the most conserved gene products of HHVs. Since the packaging protein pUL15 is the most conserved among all HHV-1 gene products, the virus will have a lower chance of developing resistance to small molecules targeting pUL15. A subsequent analysis of the structure of pUL15 revealed distinct ATP and DNA binding domains and the elastic network model identifies a functionally important hinge region between the two domains of pUL15. The atomic information on the active and allosteric sites in the ATP- and DNA-bound model of pUL15 presented in this study can inform the structure-based drug discovery of a new class of drugs to treat a wide range of HHVs

Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder:results from a randomized, controlled trial

Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6–17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners’ Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment − placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours)

Cold- and light-induced changes in the transcriptome of wheat leading to phase transition from vegetative to reproductive growth

<p>Abstract</p> <p>Background</p> <p>For plants to flower at the appropriate time, they must be able to perceive and respond to various internal and external cues. Wheat is generally a long-day plant that will go through phase transition from vegetative to floral growth as days are lengthening in spring and early summer. In addition to this response to day-length, wheat cultivars may be classified as either winter or spring varieties depending on whether they require to be exposed to an extended period of cold in order to become competent to flower. Using a growth regime to mimic the conditions that occur during a typical winter in Britain, and a microarray approach to determine changes in gene expression over time, we have surveyed the genes of the major pathways involved in floral transition. We have paid particular attention to wheat orthologues and functional equivalents of genes involved in the phase transition in <it>Arabidopsis</it>. We also surveyed all the MADS-box genes that could be identified as such on the Affymetrix genechip wheat genome array.</p> <p>Results</p> <p>We observed novel responses of several genes thought to be of major importance in vernalisation-induced phase transition, and identified several MADS-box genes that might play an important role in the onset of flowering. In addition, we saw responses in genes of the Gibberellin pathway that would indicate that this pathway also has some role to play in phase transition.</p> <p>Conclusion</p> <p>Phase transition in wheat is more complex than previously reported, and there is evidence that day-length has an influence on genes that were once thought to respond exclusively to an extended period of cold.</p