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Background: Impairments in language and communication are core features of autism spectrum disorders (ASDs). The basis for this association is poorly understood. How early language is related to each of the triad of impairments characteristic of ASDs is also in need of clarification. Aims: This is the first study that aims to determine the extent to which shared genetic and environmental factors underlie the association between early language performance and autistic-like traits (ALTs) in middle childhood. Methods & Procedures: Data came from a population-based twin sample (n = 6087 pairs) assessed prospectively at 2, 3, 4 and 8 years. ALTs measured by the Childhood Asperger Syndrome Test (CAST) at 8 years were investigated in relation to language assessed by the MacArthur Communicative Development Inventory (CDI) at 2, 3 and 4 years. Multivariate model fitting techniques were used to analyse the origins of this association. Outcomes & Results: Total CAST scores, as well as Social and Communication subscales, at 8 years were weakly but significantly negatively correlated with language ability at 2, 3 and 4 years. Correlations between language and restrictive and repetitive behaviours and interests (RRBI) were not significant. The phenotypic correlations between language and Social and Communication ALTs were almost entirely mediated by shared genetic influences. There were specific genetic influences on early language that were not shared with ALTs, and specific genetic influences on ALTs not shared with earlier language performance. Conclusions: This is the first study to demonstrate shared genetic influences in relation to language performance as an early antecedent of later ALTs. These results support the idea that the triad of core features in ALTs are aetiologically heterogeneous, with early language relating to social and communication impairments but not RRBIs. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: We declared the following interests based on NICE’s policy on conflicts of interests (https://www.nice.org.uk/Media/Default/About/Who-we-are/Policies-and-procedures/declaration-of-interests-policy.pdf): none. The guideline authors’ full statements can be viewed at https://www.nice.org.uk/guidance/ng241/history.

Importance: Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed., Objective: To estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs., Design, Setting, and Participants: In this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed., Exposures: CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention., Main Outcomes and Measures: The incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated., Results: In the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were -£1942/QALY (-$2680/QALY), -£89/QALY (-$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs., Conclusions and Relevance: In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.

Competing Interests: Competing interests: We declared the following interests based on NICE’s policy on conflicts of interests (https://www.nice.org.uk/Media/Default/About/Who-we-are/Policies-and-procedures/declaration-of-interests-policy.pdf):

Background: Acne vulgaris is a common skin condition that may cause psychosocial distress. There is evidence that topical treatment combinations, chemical peels and photochemical therapy (combined blue/red light) are effective for mild-to-moderate acne, while topical treatment combinations, oral antibiotics combined with topical treatments, oral isotretinoin and photodynamic therapy are most effective for moderate-to-severe acne. Effective treatments have varying costs. The National Institute for Health and Care Excellence (NICE) in England considers cost-effectiveness when producing national clinical, public health and social care guidance., Aim: To assess the cost-effectiveness of treatments for mild-to-moderate and moderate-to-severe acne to inform relevant NICE guidance., Methods: A decision-analytical model compared costs and quality-adjusted life-years (QALYs) of effective topical pharmacological, oral pharmacological, physical and combined treatments for mild-to-moderate and moderate-to-severe acne, from the perspective of the National Health Service in England. Effectiveness data were derived from a network meta-analysis. Other model input parameters were based on published sources, supplemented by expert opinion., Results: All of the assessed treatments were more cost-effective than treatment with placebo (general practitioner visits without active treatment). For mild-to-moderate acne, topical treatment combinations and photochemical therapy (combined blue/red light) were most cost-effective. For moderate-to-severe acne, topical treatment combinations, oral antibiotics combined with topical treatments, and oral isotretinoin were the most cost-effective. Results showed uncertainty, as reflected in the wide confidence intervals around mean treatment rankings., Conclusion: A range of treatments are cost-effective for the management of acne. Well-conducted studies are needed to examine the long-term clinical efficacy and cost-effectiveness of the full range of acne treatments., (© 2022 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Various treatments for acne vulgaris exist, but little is known about their comparative effectiveness in relation to acne severity., Objectives: To identify best treatments for mild-to-moderate and moderate-to-severe acne, as determined by clinician-assessed morphological features., Methods: We undertook a systematic review and network meta-analysis of randomized controlled trials (RCTs) assessing topical pharmacological, oral pharmacological, physical and combined treatments for mild-to-moderate and moderate-to-severe acne, published up to May 2020. Outcomes included percentage change in total lesion count from baseline, treatment discontinuation for any reason, and discontinuation owing to side-effects. Risk of bias was assessed using the Cochrane risk-of-bias tool and bias adjustment models. Effects for treatments with ≥ 50 observations each compared with placebo are reported below., Results: We included 179 RCTs with approximately 35 000 observations across 49 treatment classes. For mild-to-moderate acne, the most effective options for each treatment type were as follows: topical pharmacological - combined retinoid with benzoyl peroxide (BPO) [mean difference 26·16%, 95% credible interval (CrI) 16·75-35·36%]; physical - chemical peels, e.g. salicylic or mandelic acid (39·70%, 95% CrI 12·54-66·78%) and photochemical therapy (combined blue/red light) (35·36%, 95% CrI 17·75-53·08%). Oral pharmacological treatments (e.g. antibiotics, hormonal contraceptives) did not appear to be effective after bias adjustment. BPO and topical retinoids were less well tolerated than placebo. For moderate-to-severe acne, the most effective options for each treatment type were as follows: topical pharmacological - combined retinoid with lincosamide (clindamycin) (44·43%, 95% CrI 29·20-60·02%); oral pharmacological - isotretinoin of total cumulative dose ≥ 120 mg kg -1 per single course (58·09%, 95% CrI 36·99-79·29%); physical - photodynamic therapy (light therapy enhanced by a photosensitizing chemical) (40·45%, 95% CrI 26·17-54·11%); combined - BPO with topical retinoid and oral tetracycline (43·53%, 95% CrI 29·49-57·70%). Topical retinoids and oral tetracyclines were less well tolerated than placebo. The quality of included RCTs was moderate to very low, with evidence of inconsistency between direct and indirect evidence. Uncertainty in findings was high, in particular for chemical peels, photochemical therapy and photodynamic therapy. However, conclusions were robust to potential bias in the evidence., Conclusions: Topical pharmacological treatment combinations, chemical peels and photochemical therapy were most effective for mild-to-moderate acne. Topical pharmacological treatment combinations, oral antibiotics combined with topical pharmacological treatments, oral isotretinoin and photodynamic therapy were most effective for moderate-to-severe acne. Further research is warranted for chemical peels, photochemical therapy and photodynamic therapy for which evidence was more limited. What is already known about this topic? Acne vulgaris is the eighth most common disease globally. Several topical, oral, physical and combined treatments for acne vulgaris exist. Network meta-analysis (NMA) synthesizes direct and indirect evidence and allows simultaneous inference for all treatments forming an evidence network. Previous NMAs have assessed a limited range of treatments for acne vulgaris and have not evaluated effectiveness of treatments for moderate-to-severe acne. What does this study add? For mild-to-moderate acne, topical treatment combinations, chemical peels, and photochemical therapy (combined blue/red light; blue light) are most effective. For moderate-to-severe acne, topical treatment combinations, oral antibiotics combined with topical treatments, oral isotretinoin and photodynamic therapy (light therapy enhanced by a photosensitizing chemical) are most effective. Based on these findings, along with further clinical and cost-effectiveness considerations, National Institute for Health and Care Excellence (NICE) guidance recommends, as first-line treatments, fixed topical treatment combinations for mild-to-moderate acne and fixed topical treatment combinations, or oral tetracyclines combined with topical treatments, for moderate-to-severe acne., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Competing Interests: Competing interests: We declared the following interests based on NICE’s policy on conflicts of interests (https://www.nice.org.uk/about/who-we-are/policies-and-procedures).

Competing Interests: Competing interests: We declared the following interests based on NICE’s policy on conflicts of interests (available at link [https://www.nice.org.uk/Media/Default/Get-involved/Fellows%20and%20scholars%20unsecure/Conflicts-of-interest-policy.pdf]). Provenance and peer review: commissioned; not externally peer reviewed.

Competing Interests: Competing interests: We declared the following interests based on NICE’s policy on conflicts of interests (www.nice.org.uk/Media/Default/About/Who-we-are/Policies-and-procedures/declaration-of-interests-policy.pdf). PE: provides medico-legal reports (which may include giving an opinion on life expectancy with children with cerebral palsy); trustee of Castang Foundation, a charity that supports research and management of cerebral palsy; has published a paper on long term and social impact of hypoxic-ischaemic encephalopathy; and completed an unpaid interview with an American pharmaceutical company about improvements in outcomes for 0-6 year olds. CF: was the chair for the NICE clinical guideline “Cerebral palsy in under 25s: assessment and management”; trustee of Whizz Kidz, a charity that funds powered mobility aids for children.

Competing Interests: Competing interests: We declare the following interests based on NICE's policy on conflicts of interests (available at www.nice.org.uk/Media/Default/About/Who-we-are/Policies-and-procedures/code-of-practice-for-declaring-and-managing-conflicts-of-interest.pdf): RP received payments to present a BMJ Mastercourses webinar on common problems in newborns and infants and a webinar on feeding problems in infants, and to conduct teaching with BMJ Learning.

Objectives: To determine the cost-effectiveness of natriuretic peptide (NP) testing and specialist outreach in patients with acute heart failure (AHF) residing off the cardiology ward., Methods: We used a Markov model to estimate costs and quality-adjusted life-years (QALYs) for patients presenting to hospital with suspected AHF. We examined diagnostic workup with and without the NP test in suspected new cases, and we examined the impact of specialist heart failure outreach in all suspected cases. Inputs for the model were derived from systematic reviews, the UK national heart failure audit, randomized controlled trials, expert consensus from a National Institute for Health and Care Excellence guideline development group, and a national online survey. The main benefit from specialist care (cardiology ward and specialist outreach) was the increased likelihood of discharge on disease-modifying drugs for people with left ventricular systolic dysfunction, which improve mortality and reduce re-admissions due to worsened heart failure (associated with lower utility). Costs included diagnostic investigations, admissions, pharmacological therapy, and follow-up heart failure care., Results: NP testing and specialist outreach are both higher cost, higher QALY, cost-effective strategies (incremental cost-effectiveness ratios of £11,656 and £2,883 per QALY gained, respectively). Combining NP and specialist outreach is the most cost-effective strategy. This result was robust to both univariate deterministic and probabilistic sensitivity analyses., Conclusions: NP testing for the diagnostic workup of new suspected AHF is cost-effective. The use of specialist heart failure outreach for inpatients with AHF residing off the cardiology ward is cost-effective. Both interventions will help improve outcomes for this high-risk group., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Many stroke survivors, despite improvements in mortality and morbidity, remain dependent on others for everyday activities. People with stroke need access to effective specialist multidisciplinary rehabilitation services that are organised and integrated within the whole system of health and social care. They also commonly come under the care of generalists in various clinical contexts, including intercurrent illness. This Clinical Medicine Concise Guideline abstracts key recommendations from the National Institute for Health and Care Excellence Clinical Guideline 162 on stroke rehabilitation of particular relevance to clinicians in general medicine, to inform their front-line practice and promote liaison and collaboration with the specialist service., (© Royal College of Physicians 2015. All rights reserved.)

Objectives: To determine and compare the diagnostic accuracy of serum natriuretic peptide levels (B type natriuretic peptide, N terminal probrain natriuretic peptide (NTproBNP), and mid-regional proatrial natriuretic peptide (MRproANP)) in people presenting with acute heart failure to acute care settings using thresholds recommended in the 2012 European Society of Cardiology guidelines for heart failure., Design: Systematic review and diagnostic meta-analysis., Data Sources: Medline, Embase, Cochrane central register of controlled trials, Cochrane database of systematic reviews, database of abstracts of reviews of effects, NHS economic evaluation database, and Health Technology Assessment up to 28 January 2014, using combinations of subject headings and terms relating to heart failure and natriuretic peptides., Eligibility Criteria for Selecting Studies: Eligible studies evaluated one or more natriuretic peptides (B type natriuretic peptide, NTproBNP, or MRproANP) in the diagnosis of acute heart failure against an acceptable reference standard in consecutive or randomly selected adults in an acute care setting. Studies were excluded if they did not present sufficient data to extract or calculate true positives, false positives, false negatives, and true negatives, or report age independent natriuretic peptide thresholds. Studies not available in English were also excluded., Results: 37 unique study cohorts described in 42 study reports were included, with a total of 48 test evaluations reporting 15 263 test results. At the lower recommended thresholds of 100 ng/L for B type natriuretic peptide and 300 ng/L for NTproBNP, the natriuretic peptides have sensitivities of 0.95 (95% confidence interval 0.93 to 0.96) and 0.99 (0.97 to 1.00) and negative predictive values of 0.94 (0.90 to 0.96) and 0.98 (0.89 to 1.0), respectively, for a diagnosis of acute heart failure. At the lower recommended threshold of 120 pmol/L, MRproANP has a sensitivity ranging from 0.95 (range 0.90-0.98) to 0.97 (0.95-0.98) and a negative predictive value ranging from 0.90 (0.80-0.96) to 0.97 (0.96-0.98). At higher thresholds the sensitivity declined progressively and specificity remained variable across the range of values. There was no statistically significant difference in diagnostic accuracy between plasma B type natriuretic peptide and NTproBNP., Conclusions: At the rule-out thresholds recommended in the 2012 European Society of Cardiology guidelines for heart failure, plasma B type natriuretic peptide, NTproBNP, and MRproANP have excellent ability to exclude acute heart failure. Specificity is variable, and so imaging to confirm a diagnosis of heart failure is required. There is no statistical difference between the diagnostic accuracy of plasma B type natriuretic peptide and NTproBNP. Introduction of natriuretic peptide measurement in the investigation of patients with suspected acute heart failure has the potential to allow rapid and accurate exclusion of the diagnosis., (© Roberts et al 2015.)

Objective: This study aimed to explore sex differences in autistic traits in relation to diagnosis, to elucidate factors that might differentially impact whether girls versus boys meet diagnostic criteria for autism or a related autism spectrum disorder (ASD)., Method: Data from a large population-based sample of children were examined. Girls and boys (aged 10-12 years) meeting diagnostic criteria for an ASD were compared with those failing to meet diagnostic criteria despite very high scores on a trait measure of ASD, the Childhood Autism Spectrum Test (CAST). Information about behavioral difficulties as reported by teachers, and early estimates of intellectual functioning, were compared., Results: Girls, but not boys, meeting diagnostic criteria for ASD showed significantly more additional problems (low intellectual level, behavioral difficulties) than peers with similarly high CAST scores who did not meet diagnostic criteria., Conclusions: These data suggest that, in the absence of additional intellectual or behavioral problems, girls are less likely than boys to meet diagnostic criteria for ASD at equivalently high levels of autistic-like traits. This might reflect gender bias in diagnosis or genuinely better adaptation/compensation in girls., (Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Stuttering affects approximately 5% of children up to the teenage years. There are many possible forms of intervention, one of which is pharmacotherapy. No review about the treatment of stuttering with pharmacological agents in children and adolescents has been undertaken. The objectives of this review were to determine the extent of previous research in this area and to assess the success of pharmacological agents in reducing the frequency of disfluency in child and adolescent stutterers (<18 years). A systematic search of MEDLINE, PsychInfo, Embase, and Cochrane Systematic Review databases was carried out to identify potential studies for the review. Studies that met specified criteria were selected for detailed examination, and the quality of evidence they provided was assessed according to 7 criteria that pertained to study design and data provision. Seven publications met the inclusion criteria for the review. Only 1 publication was classified as strong evidence quality, and this reported that clonidine did not reduce the frequency of disfluency in a group of 25 individuals who stuttered. All further publications were classified as either very low or low evidence quality. The agents examined were risperidone, olanzapine, clonidine, tiapride, haloperidol, and chlorpromazine.

Background: It has been questioned whether the process of twinning might be a risk factor for autism spectrum conditions (ASC) and autistic traits., Aim: We sought to determine whether autistic traits and probable disorder, as measured by the Childhood Autism Spectrum Test (CAST), were more pronounced in twins compared to singletons., Samples: Data were analyzed from two large population-based samples of UK children, twins (n = 5,142 twin pairs, aged 8 years) and singletons (n = 2,805, aged 5-9 years)., Results: Distributions of CAST scores in both groups were negatively skewed and scores for twins were more variable than singletons. Mean CAST total scores and standard errors (SE) were not significantly different for twins (5.1; SE 0.04) compared to singletons (4.9; SE 0.08). Moreover, contrary to expectations, the likelihood of scoring above the threshold for possible ASC was significantly lower in the twins than the singletons (OR = 0.69; P = 0.002). Subsidiary analyses of CAST scores according to sex, twin type, and subscale scores representing the subdomains of autism found a few significant differences (P<0.01), but the effect sizes for these differences were small and none exceeded η(2) = 0.005. The explanation for these small differences remains obscure, but the very small effect sizes mean they are of little importance., Conclusions: Our results do not provide evidence to support twinning as a risk factor in the development of autistic traits., (Copyright © 2011, International Society for Autism Research, Wiley-Liss, Inc.)

Aim: A deficit in non-word repetition (NWR), a measure of short-term phonological memory proposed as a marker for language impairment, is found not only in language impairment but also in reading impairment. We evaluated the strength of association between language impairment and reading impairment in children with current, past, and no language impairment and assessed any differential impairment of NWR, compared with two other tests of verbal memory in children with language impairment with and without reading impairment., Method: Our sample comprised children aged 6-16y 11mo participating in a study of the genetics of language impairment: 78 children from 68 families (53 males, 25 females) with current language impairment (C-LI), compared with their 74 siblings: 25 children (18 males, seven females) with a past history of language impairment and 49 children (27 males, 22 females) who had never had a language impairment. The tests used were the Clinical Evaluation of Language Fundamentals (CELF III), the Children's Test of Non-word Repetition (CN-Rep), the Wide Range Assessment of Memory and Learning (WRAML) verbal memory index, the Wechsler Intelligence Scale for Children-III (WISC-III) digit span, and the Wechsler Objective Reading Dimensions (WORD(UK) )., Results: Reading impairment was present in two-thirds of the children with current language impairment. NWR deficits were significantly worse in children with language impairment who had reading impairment in reading decoding (p=0.007 and 0.004 - average group compared with borderline and definitely impaired groups respectively) or spelling (p=0.002 and 0.005 - average group compared with borderline and severely impaired groups respectively) (not correlated with severity of language impairment) but not comprehension impairment. In contrast, WISC digit span and WRAML verbal memory were impaired in all children with language impairment and did not differentiate those who also had reading impairment., Interpretation: We suggest that current NWR ability may be a marker of a process specifically underlying language impairment, co-occurring with reading impairment involving reading decoding and spelling, rather than a generic correlate of language impairment. Other verbal memory deficits appear to be pervasive in children with language impairment., (© The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.)

Aim: The aim of this study was to assess whether any memory impairment co-occurring with language impairment is global, affecting both verbal and visual domains, or domain specific., Method: Visual and verbal memory, learning, and processing speed were assessed in children aged 6 years to 16 years 11 months (mean 9 y 9 m, SD 2 y 6 mo) with current, resolved, and no language impairment using the Wide Range Assessment of Memory and Learning (WRAML), a standardized memory and learning test for children, and the Children's Test of Non-Word Repetition (CNRep), a test of phonological short-term memory. Fifty-one children (38 males, 13 females) with current speech and language impairment from 49 families were compared with 13 siblings (11 males, 2 females) with a past history of language impairment and 26 (15 males, 11 females) who had never had language impairment., Results: Children with current language impairment showed impairment in all verbal memory measures compared with children who had never had language impairment, and these impairments were still evident in children with a past history of learning impairment. Visual memory and learning were not impaired compared with children who had never had language impairment. The severity of verbal memory impairment correlated with the degree of language impairment., Interpretation: We concluded that in language impairment there is domain specificity of memory impairment affecting verbal processing.

We investigated the relationship between challenging behavior and co-morbid psychopathology in adults with intellectual disability (ID) and autism spectrum disorders (ASDs) (N=124) as compared to adults with ID only (N=562). All participants were first time referrals to specialist mental health services and were living in community settings. Clinical diagnoses were based on ICD-10 criteria and presence of challenging behavior was assessed with the Disability Assessment Schedule (DAS-B). The analyses showed that ASD diagnosis was significantly associated with male gender, younger age and lower level of ID. Challenging behavior was about four times more likely in adults with ASD as compared to non-ASD adults. In those with challenging behavior, there were significant differences in co-morbid psychopathology between ASD and non-ASD adults. However, after controlling for level of ID, gender and age, there was no association between co-morbid psychopathology and presence of challenging behavior. Overall, the results suggest that presence of challenging behavior is independent from co-morbid psychopathology in adults with ID and ASD., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Prenatal and neonatal events were reported by parents of 13,690 eighteen-month-old twins enrolled in the Twins Early Development Study, a representative community sample born in England and Wales. At ages 7-8, parents and teachers completed questionnaires on social and nonsocial autistic-like features and parents completed the Childhood Asperger Syndrome Test. Correlations between prenatal and neonatal events and autistic-like features were weak, both in the whole sample (r = .00-.07) and at the 5% quantitative extreme (phenotypic group correlations = .01-.11), after controlling for socioeconomic status and cognitive ability. Neonatal problems showed modest heritability (13%-14%) and significant shared and nonshared environmental influences (55%-59% and 28%-31%, respectively). Differences in identical twins' neonatal problems correlated weakly with their difference scores on autistic-like features (r = .01-.06).

Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 x 10(-7) at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 x 10(-5) at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition.

Factor structure and relationship between core features of autism (social impairments, communication difficulties, and restricted, repetitive behaviours or interests (RRBIs)) were explored in 189 children from the Twins Early Development Study, diagnosed with autistic spectrum disorders (ASDs) using the Development and Wellbeing Assessment (DAWBA; Goodman et al. in J Child Psychol Psyc 41:645-655, 2000). A bottom-up approach (analysis 1) used principal component factor analysis of DAWBA items indicating five factors, the first three mapping on the triad. In analysis 2, applying top-down DSM-IV criteria, correlations between domains were modest, strongest between social and communication difficulties. Cross-twin cross-trait correlations suggested small shared genetic effects between RRBIs and other symptoms. These findings from a clinical sample of twins indicate a fractionation of social/communicative and RRBI symptoms in ASD.

Purpose: The contribution of genetic factors in the persistence of and early recovery from stuttering was assessed., Method: Data from the Twins Early Development Study were employed. Parental reports regarding stuttering were collected at ages 2, 3, 4, and 7 years, and were used to classify speakers into recovered and persistent groups. Of 12,892 children with at least 2 ratings, 950 children had recovered and 135 persisted in their stutter., Results: Logistic regressions showed that the rating at age 2 was not predictive of later stuttering, whereas ratings at ages 3 and 4 were. Concordance rates were consistently higher for monozygotic than for dizygotic twin pairs (with the exception of girls at age 3). At 3, 4, and 7 years, the liability to stuttering was highly heritable (h2 estimates of between .58 and .66). Heritability for the recovered and persistent groups was also high but did not differ from each other., Conclusion: Stuttering appears to be a disorder that has high heritability and little shared environment effect in early childhood and for recovered and persistent groups of children, by age 7. The clinical implications of the findings are discussed.

Imitation, vocabulary, pretend play, and socially insightful behavior were investigated in 5,206 same- and opposite-sex 2-year-old twin pairs in the United Kingdom. Individual differences in imitative ability were due to modest heritability (30%), while environmental factors shared between twins (42%) and unique to each twin (28%) also made significant contributions to the variance. Imitation correlated significantly, although modestly, with vocabulary, pretend play, and socially insightful behavior, and the strongest relationship was with vocabulary. A model that represented the covariance between the variables as being due to correlated latent genetic and environmental factors fitted the data well, with shared environmental factors influencing most of the covariance. Parents who encourage imitation may also tend to foster the development of language, pretence, and socially insightful behavior.

In 4 experiments, the authors addressed the mechanisms by which grammatical gender (in Italian and German) may come to affect meaning. In Experiments 1 (similarity judgments) and 2 (semantic substitution errors), the authors found Italian gender effects for animals but not for artifacts; Experiment 3 revealed no comparable effects in German. These results suggest that gender effects arise as a generalization from an established association between gender of nouns and sex of human referents, extending to nouns referring to sexuated entities. Across languages, such effects are found when the language allows for easy mapping between gender of nouns and sex of human referents (Italian) but not when the mapping is less transparent (German). A final experiment provided further constraints: These effects during processing arise at a lexical-semantic level rather than at a conceptual level., (Copyright (c) 2005 APA, all rights reserved.)

Recent research into stuttering in English has shown that function word disfluency decreases with age whereas content words disfluency increases. Also function words that precede a content word are significantly more likely to be stuttered than those that follow content words (Au-Yeung, Howell and Pilgrim, 1998; Howell, Au-Yeung and Sackin, 1999). These studies have used the concept of the phonological word as a means of investigating these phenomena. Phonological words help to determine the position of function words relative to content words and to establish the origin of the patterns of disfluency with respect to these two word classes. The current investigation analysed German speech for similar patterns. German contains many long compound nouns; on this basis, German content words are more complex than English ones. Thus, the patterns of disfluency within phonological words may differ between German and English. Results indicated three main findings. Function words that occupy an early position in a PW have higher rates of disfluency than those that occur later in a PW, this being most apparent for the youngest speakers. Second, function words that precede the content word in a PW have higher rates of disfluency than those that follow the content word. Third, young speakers exhibit high rates of disfluency on function words, but this drops off with age and, correspondingly, disfluency rate on content words increases. The patterns within phonological words may be general to German and English and can be accounted for by the EXPLAN model, assuming lexical class operates equivalently across these languages or that lexical categories contain some common characteristic that is associated with fluency across the languages.

Unlabelled: This study investigated how phonetic complexity affects stuttering rate in German and how this changes developmentally. Phonetic difficulty was assessed using Jakielski's index [Motor Organization in the Acquisition of Consonant Clusters, Dissertation/Ph.D. Thesis, University of Texas Austin, 1998] of phonetic complexity (IPC) in which words are scored on eight different characteristics. Stuttering rate was not related to IPC score for German function words, as previously shown for Spanish and English. Significant correlations between stuttering rate and IPC score were found for content words for children over the age of six and adults. It was also found that German content words have a higher mean IPC sum compared to their English counterparts. There was a bigger difference in IPC score between fluent and stuttered words in German than in English. Factor 5 (word shape) influenced stuttering rates in both German age groups. This has also been found for Spanish but does not apply to English., Educational Objectives: The reader will be able to: (1) describe a method to measure phonetic complexity and how this affects stuttering rates for words of different grammatical classes; (2) explain why this method is suitable for different languages and age groups; (3) detect which phonetic characteristics have most impact on different age groups in English and German; (4) assess possible theoretical reasons for these findings.

Borden's (1979, 1980) hypothesis that speakers with vulnerable speech systems rely more heavily on feedback monitoring than do speakers with less vulnerable systems was investigated. The second language (L2) of a speaker is vulnerable, in comparison with the native language, so alteration to feedback should have a detrimental effect on it, according to this hypothesis. Here, we specifically examined whether altered auditory feedback has an effect on accent strength when speakers speak L2. There were three stages in the experiment. First, 6 German speakers who were fluent in English (their L2) were recorded under six conditions--normal listening, amplified voice level, voice shifted in frequency, delayed auditory feedback, and slowed and accelerated speech rate conditions. Second, judges were trained to rate accent strength. Training was assessed by whether it was successful in separating German speakers speaking English from native English speakers, also speaking English. In the final stage, the judges ranked recordings of each speaker from the first stage as to increasing strength of German accent. The results show that accents were more pronounced under frequency-shifted and delayed auditory feedback conditions than under normal or amplified feedback conditions. Control tests were done to ensure that listeners were judging accent, rather than fluency changes caused by altered auditory feedback. The findings are discussed in terms of Borden's hypothesis and other accounts about why altered auditory feedback disrupts speech control.