Squaric esters as peptide stapling reagents.

We report that squaric esters can serve as bifunctional reagents for selective peptide stapling reactions. Formation of the squaric amide staple occurs under mild conditions with amine-containing side chains. We show that short resin-bound peptides are readily stapled on solid phase and that stapling can occur at various relative positions along the peptide and with various amine tether lengths (e.g. Lysine, ornithine, etc). The squaric amide staples are stable to strong acid conditions used to cleave the stapled peptide from the resin and the stapled peptides show an increase in helicity as analyzed through circular dichroism.

Erratum: One welfare: Linking poverty, equid ownership and equid welfare in the brick kilns of India - ERRATUM.

[This corrects the article DOI: 10.1017/S0962728600032504.].

The meaning of play for children and young people with physical disabilities: A systematic thematic synthesis.

BACKGROUND: Children and young people with physical disabilities are often reported to play less than their typically developing peers. Few studies explore the meaning of play from the child's perspective; this study carried out a thematic synthesis of the findings of qualitative studies about the meaning of play following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: A search of CINAHL, AHMED, PsycINFO, MEDLINE, EMBASE, and ERIC was undertaken between September 2015 and March 2016. Qualitative studies exploring the meaning of play from the perspective of 0- to 18-year-olds with physical disabilities impacting function were included. Quality appraisal and thematic synthesis were undertaken in order to develop analytical themes. RESULTS: Thirteen studies met the inclusion criteria in part addressing the meaning of play for children and young people with physical disabilities. Synthesis of the findings identified 5 analytical themes: Play can feel both positive and negative; play can draw attention towards or away from my disability; play is a social interaction; I participate differently to my peers, and needing help feels normal. CONCLUSIONS: The themes highlight the potential for play experiences of individuals with physical disabilities being overlooked by parents and professionals; further research is needed to explore play experience from these individual's perspective.

Evidence for the effectiveness of botulinum toxin for spasmodic dysphonia from high-quality research designs.

The practice of evidence-based medicine promotes use of the knowledge ascertained from high quality research designs. The objective of this review was to determine what evidence has been provided from high quality research designs (e.g., randomized control trials or high quality prospective, matched group cohort studies), through December of 2006, relative to the effectiveness of botulinum toxin for treating spasmodic dysphonia. Results of the review indicated that no new high quality (Class I or Class II) studies have been published since 2001. One Class I study has been published since 1973, which found significant treatment effects for acoustic and perceptual variables of vocal function. Four Class II studies have been published during this same time frame, all finding significant treatment effects, though the nature of studied factors was variable between investigations. Based on the quality of evidence scale used, botulinum toxin can be considered an effective treatment for adductor spasmodic dysphonia.

Combined vitamin B6-magnesium treatment in autism spectrum disorder.

BACKGROUND: The use of mega-vitamin intervention began in the 1950s with the treatment of schizophrenic patients. Pyroxidine (vitamin B6) was first used with children diagnosed with "autism syndrome" when speech and language improvement was observed in some children as a result of large doses of B6. A number of studies attempted to assess the effects of vitamin B6-Magnesium (Mg) was found to reduce undesirable side effects from B6) on characteristics such as verbal communication, non-verbal communication, interpersonal skills, and physiological function, in individuals with autism. OBJECTIVES: To determine the efficacy of vitamin B6 and magnesium (B6-Mg) for treating social, communication, and behavioural responses of children and adults with autism. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), MEDLINE (1966 to January 2002), EMBASE (1980 to January 2002), PsycINFO (1887 to January 2002), Dissertation Abstracts International (1861 to January 2002). The search engine FirstSearch was also used (January 2002). All searches were updated in April 2005. Reference lists for all the obtained studies and other review articles were examined for additional studies. SELECTION CRITERIA: All studies in which the participants had been diagnosed with autistic spectrum disorder were randomly allocated prior to intervention and in which outcomes were compared to either a placebo or non-treated group were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated and extracted data from all potential studies identified for inclusion. MAIN RESULTS: This update includes a new trial (Kuriyama 2002) to bring the total of included studies to three (total n=33). One study, which used a cross-over design (Tolbert 1993) provided insufficient data to conduct an analysis. Another crossover study (Findling 1997) yielded no significant differences between treatment and placebo group performances following the B6 intervention on measures of social interaction, communication, compulsivity, impulsivity, or hyperactivity. The latest study (Kuriyama 2002) was motivated by evidence from epilepsy research and was focussed on a subgroup of children with pervasive developmental disorders (PDDs) who exhibited clinical features similar to those with pyroxidine-dependent epilepsy. This small study (n=8) only measured IQ and 'Social Quotient' and found a statistically significant benefit for IQ (5.2, 95% CI = [0.2 to 10.3]) when in the treated group, by using change scores. AUTHORS' CONCLUSIONS: Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism.

Botulinum toxin injections for the treatment of spasmodic dysphonia.

BACKGROUND: The use of botulinum toxin for the treatment of spasmodic dysphonia is currently the treatment of choice for management of this neurological voice disorder. Over the past 20 years, botulinum toxin has been used to treat both adductor and abductor forms of the disorder, with vocal improvement noted after treatment for both. A large number of studies have attempted to document the efficacy of botulinum toxin for improvement of vocal symptoms in individuals with spasmodic dysphonia. OBJECTIVES: To determine the effectiveness of botulinum toxin for treating spasmodic dysphonia. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to July 2003), EMBASE (1974 to July 2003 ), CINAHL (through July 2003), Dissertation Abstracts International (1975 to July 2003) and PsycINFO (1975 to July 2003). The search engine FirstSearch was also used (July 2003). Reference lists for all the obtained studies and other review articles were examined for additional studies. SELECTION CRITERIA: All studies in which the participants were randomly allocated prior to intervention and in which botulinum toxin was compared to either an alternative treatment, placebo or non-treated control group were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated all potential studies meeting the selection criteria noted above for inclusion. One study met the inclusion criteria and was included in the final analysis. MAIN RESULTS: Only one study in the literature met the inclusion criteria. This was the only study identified which reported a treatment/no treatment comparison. It reported significant beneficial effects for fundamental frequency (Fo), Fo Range, spectrographic analysis, independent ratings of voice severity and patient ratings of voice improvement. REVIEWERS' CONCLUSIONS: The evidence from randomized controlled trials does not allow firm conclusions to be drawn about the effectiveness of botulinum toxin for all types of spasmodic dysphonia, or for patients with different behavioral or clinical characteristics.

Speech and language therapy interventions for children with primary speech and language delay or disorder.

BACKGROUND: It is thought that approximately 6% of children have speech and language difficulties of which the majority will not have any other significant developmental difficulties. Whilst most children's difficulties resolve, children whose difficulties persist into primary school may have long-term problems concerning literacy, socialisation, behaviour and school attainment. OBJECTIVES: To examine the effectiveness of speech and language interventions for children with primary speech and language delay/disorder. SEARCH STRATEGY: The following databases were searched: The Cochrane Controlled Trials Register (Cochrane Library, CENTRAL: 2002/3), CINAHL (1982 - July 2002), EMBASE (1980 - Sept Week 4 2002), ERIC (1965 - 2002), MEDLINE (1966 - Sept Week 3 2002), PsycINFO (1872 - 2002/10 Week 2), The National Research Register (2002/3). In addition to this references were taken from reviews of the literature and reference lists from articles. SELECTION CRITERIA: The review considered randomised controlled trials of speech and language therapy interventions for children or adolescents with primary speech and language delay/disorder. DATA COLLECTION AND ANALYSIS: Titles and abstracts were identified and assessed for relevance, before the full text version was obtained of all potentially relevant articles. The data were categorised depending on the nature of the control group and considered in terms of the effects of intervention on expressive and receptive phonology, syntax and vocabulary. The outcomes used in the analysis were dependent on the focus of the study with only the primary effects of therapy being considered in this review. MAIN RESULTS: The results of twenty-five studies were used in the meta-analysis. The results suggest that speech and language therapy is effective for children with phonological (SMD=0.44, 95%CI: 0.01,0.86) or vocabulary difficulties (SMD=0.89, 95%CI: 0.21,1.56), but that there is less evidence that interventions are effective for children with receptive difficulties (SMD=-0.04, 95%CI: -0.64,0.56). Mixed findings were found concerning the effectiveness of expressive syntax interventions (n=233; SMD=1.02, 95%CI: 0.04-2.01). No significant differences were shown between clinician administered intervention and intervention implemented by trained parents, and studies did not show a difference between the effects of group and individual interventions (SMD=0.01, 95%CI: -0.26,1.17). The use of normal language peers in therapy was shown to have a positive effect on therapy outcome (SMD=2.29, 95%CI: 1.11,3.48). REVIEWER'S CONCLUSIONS: The review shows that overall there is a positive effect of speech and language therapy interventions for children with expressive phonological and expressive vocabulary difficulties. The evidence for expressive syntax difficulties is more mixed, and there is a need for further research to investigate intervention for receptive language difficulties. There is a large degree of heterogeneity in the results, and the sources of this need to be investigated.

Combined vitamin B6-magnesium treatment in autism spectrum disorder.

BACKGROUND: The use of mega-vitamin intervention began in the early 1950's with the treatment of schizophrenic patients. Pyroxidine (vitamin B6) was first used with children diagnosed with "autism syndrome" when speech and language improvement was observed in some children as a result of large doses of B6. A number of published studies attempted to assess the effects of vitamin B6-Mg (Mg was found to reduce undesirable side effects from B6) on a variety of characteristics such as verbal communication, non-verbal communication, interpersonal skills, and physiological function, in individuals with autism. OBJECTIVES: To determine the efficacy of vitamin B6 and magnesium (B6-Mg) for treating social, communication and behavioural responses of children and adults with autism. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), MEDLINE (1966- January 2002), EMBASE (1980-January 2002), PsychINFO (1887 - January 2002), Dissertation Abstracts International (1861 - January 2002). The search engine FirstSearch was also used (January 2002). Reference lists for all the obtained studies and other review articles were examined for additional studies. SELECTION CRITERIA: All studies in which the participants were randomly allocated prior to intervention and in which outcomes were compared to either a placebo or non-treated group were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated all potential studies identified as indicated above for inclusion. MAIN RESULTS: Two trials were included in the review. Both studies used a double-blind crossover design. One study (Tolbert 1993) provided insufficient data to conduct an analysis. The senior author was contacted for supporting data but was unable to provide the needed information. The remaining study (Findling, 1997) yielded no significant differences between treatment and placebo group performances following the B6 intervention on measures of social interaction, communication, compulsivity, impulsivity, or hyperactivity. REVIEWER'S CONCLUSIONS: Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism.

Successful Medicaid managed care organizations: it is not an oxymoron.

Success as a Medicaid health plan is achieved by those plans with a clear understanding of Medicaid program requirements. Executives of Medicaid health plans identify four common elements that result in winning plans: (1) Leadership must have significant experience with, or otherwise develop knowledge of, the Medicaid program's regulations and populations covered; (2) the plan must have an internal managed care culture and system that integrates finance, operations, and medical management; (3) management must have access to highly specialized information and data analysis capability; (4) leadership must have well-developed relationships with key stakeholders. While these elements seem intuitive, health plans often enter the marketplace without needed groundwork firmly in place.

Prevalence and natural history of primary speech and language delay: findings from a systematic review of the literature.

The prevalence and the natural history of primary speech and language delays were two of four domains covered in a systematic review of the literature related to screening for speech and language delay carried out for the NHS in the UK. The structure and process of the full literature review is introduced and criteria for inclusion in the two domains are specified. The resulting data set gave 16 prevalence estimates generated from 21 publications and 12 natural history studies generated from 18 publications. Results are summarized for six subdivisions of primary speech and language delays: (1) speech and/or language, (2) language only, (3) speech only, (4) expression with comprehension, (5) expression only and (6) comprehension only. Combination of the data suggests that both concurrent and predictive case definition can be problematic. Prediction improves if language is taken independently of speech and if expressive and receptive language are taken together. The results are discussed in terms of the need to develop a model of prevalence based on risk of subsequent difficulties.

Intraocular pressure, anterior chamber depth and axial length following intravenous mannitol.

The intraocular pressure (IOP), anterior chamber depth (ACD), and axial length (AL) were measured in 38 eyes of 19 subjects before and after intravenous mannitol injection (12.5 g). Intraocular pressures dropped over the initial 30 min then rose back to baseline by 2 hr. Time 0 min:14.2 mmHg, 15 min:12.7 mmHg, 30 min:11.4 mmHg, 60 min:12.0 mmHg, 90 min, 13.2 mmHg, 120 min:14.1 mmHg. Sitting and supine ACD and AL did not change following mannitol injection. This study supports an ocular hypotensive effect of mannitol without reducing vitreous volume using a relatively low dose of mannitol (12.5 g). This finding has important implications for its use in ocular surgery at this dosage.

The feasibility of universal screening for primary speech and language delay: findings from a systematic review of the literature.

This paper reports on a systematic review of the literature commissioned to examine the feasibility of universal screening for speech and language delay. The results, based on an examination of productivity figures, including positive predictive ability and likelihood ratio, indicate that a number of screening tests are adequate. Sensitivity was generally lower than specificity, and study quality was inversely related to both sensitivity and likelihood ratio, suggesting that it is easier to identify accurately children who do not have language and speech problems than those who do. The review concluded that there is insufficient evidence to warrant the introduction of universal screening at this stage. This paper discusses the type of data that would be needed to address this issue further and recommendations are made for alternative approaches to early identification.

Early family-based intervention in the path to alcohol problems: rationale and relationship between treatment process characteristics and child and parenting outcomes.

OBJECTIVE: Risk for subsequent development of alcohol problems is not uniform across the population of alcoholic families, but varies with parental comorbidity and family history. Recent studies have also identified disruptive child behavior problems in the preschool years as predictive of alcoholism in adulthood. Given the quality of risk structure in highest risk families, prevention programming is more appropriately family based rather than individual. METHOD: A family-based intervention program for the prevention of conduct problems among preschool-age sons of alcoholic fathers was implemented to change this potential mediating risk structure. A population-based recruitment strategy enrolled 52 alcoholic families in a 10-month intervention involving parent training and marital problem solving. The study examined the interplay between parent treatment investment and parent and therapist expectations and satisfaction in predicting change in child behavior and authoritative parenting style during the program, and for 6 months afterward among the 29 families whose sustained involvement allowed these effects to be evaluated. RESULTS: Parent expectations at pretreatment influenced their early investment in the program, which in turn predicted child and parenting outcomes. Parent and therapist satisfaction ratings during treatment were associated with one another and with expectations that the program would continue to promote changes in their child. Parent investment was a particularly salient influence on outcome, as higher investment throughout the program was associated with improvement in child behavior and authoritative parenting at termination. CONCLUSIONS: Findings indicate that treatment process characteristics mediate the influence of baseline parent functioning on treatment success and that treatment changes themselves predict later child outcomes.

Screening for primary speech and language delay: a systematic review of the literature.

Screening young children for developmental conditions such as speech and language delay is considered to be a part of the Child Health Surveillance programme in the UK. It is currently practised in many different ways throughout the country and like screening for other conditions conventionally identified in infancy, has been the subject of some concern for those responsible for providing such services. This systematic review (Law et al. 1998) was hypothesis driven and aimed to: i) establish whether, given the available evidence, there was sufficient evidence to warrant the introduction of universal screening for speech and language delays in children up to seven years of age; ii) identify gaps in the available literature; iii) identify priority areas in need of further investigation and iv); provide evidence-based recommendations for the future provision of services.

Meta-analysis of botulinum toxin treatment of spasmodic dysphonia: a review of 22 studies.

This meta-analysis focuses on the treatment effects of the use of botulinum toxin in laryngeal dystonia. The vocal symptoms are characterized by spasms of the laryngeal muscles thus the use of the term spasmodic dysphonia (SD). The objective of the intervention, i.e. botulinum toxin treatment, is to reduce or eliminate the vocal spasms and thus improve the acoustic regularity of the voice. The purpose of the present study was to assess the efficacy of botulinum toxin in the treatment of SD by engaging in a 'best synthesis' systematic summary of existing research. The average treated SD patient in the 22 studies subjected to meta-analysis obtained 97% improvement as a result of treatment with botulinum toxin.

The utility of meta-analysis in the determination of efficacy of treatment in aphasia: a reply to Robey (1994).

In response to Robey (1994) we argue that his judgment of our study and conclusions (Whurr, Lorch, & Nye, 1992) are inaccurate. We point out that our study was in fact an analysis of the effects of treatment for aphasic patients. Further, the results obtained in Robey's analysis, though obtained via a different strategy of analysis, yielded essentially the same degree of overall treatment outcome effect. Thus, we conclude that while Robey does provide a different model of effect size data organization and measurement, the results are no different and do not in fact contradict our data.

Acoustic characteristics of children who speak Arabic.

The vocal characteristics of mean fundamental frequency, jitter, shimmer, harmonics-to-noise ratio, and breathiness were analyzed in 110 (F = 54, M = 56) Arabic-speaking children. The subjects were from Amman, Jordan, ranging in age from 5 to 20 years. Each subject was tape recorded during the production of the vowels /a/ and /i/. Two second samples of each vowel were analyzed using GW Instrument's Sound Scope software program. Means, standard deviations, and ranges were obtained and summarized for the acoustic measures in each age and gender category.

Witelo--Polish vision scientist of the middle ages: father of physiological optics.

Unknown to the Western hemisphere, a Polish scientist, naturalist, anatomist, physiologist, philosopher and optician, Witelo, wrote an important ten volume manuscript, Peri-Optikes, usually cited in the literature as Perspectiva. This classic textbook was first published in 1535 in Nuremberg under the title: Vitellionis mathematici doctissimi ... vulgo Perspectivam vocant libri X, which is translated to English as Perspectiva. It was a vital source of information for such scientists as Leonardo da Vinci, Keppler and others in the next few centuries. Although many of his ideas were similar to Alhazan's, who earlier had written a significant optical manuscript De aspectibus, Witelo developed his own interpretation of many optical issues. He was one of the first scientists to discover spherical aberration of concave lenses and concave mirrors. He was also first to point out "that deflection of the light ray increases with the angle in which they approach two different optical substances and each increase is smaller than the previous one." Until recently, Witelo's achievements and contributions to the understanding of optical and anatomical aspects of the eye and visual function have remained unknown in western literature. Undoubtedly, Witelo should be recognized as the father of physiological optics.