Utility of Percentage Signal Recovery and Baseline Signal in DSC-MRI Optimized for Relative CBV Measurement for Differentiating Glioblastoma, Lymphoma, Metastasis, and Meningioma.

BACKGROUND AND PURPOSE: The percentage signal recovery in non-leakage-corrected (no preload, high flip angle, intermediate TE) DSC-MR imaging is known to differ significantly for glioblastoma, metastasis, and primary CNS lymphoma. Because the percentage signal recovery is influenced by preload and pulse sequence parameters, we investigated whether the percentage signal recovery can still differentiate these common contrast-enhancing neoplasms using a DSC-MR imaging protocol designed for relative CBV accuracy (preload, intermediate flip angle, low TE). MATERIALS AND METHODS: We retrospectively analyzed DSC-MR imaging of treatment-naïve, pathology-proved glioblastomas (n = 14), primary central nervous system lymphomas (n = 7), metastases (n = 20), and meningiomas (n = 13) using a protocol designed for relative CBV accuracy (a one-quarter-dose preload and single-dose bolus of gadobutrol, TR/TE = 1290/40 ms, flip angle = 60° at 1.5T). Mean percentage signal recovery, relative CBV, and normalized baseline signal intensity were compared within contrast-enhancing lesion volumes. Classification accuracy was determined by receiver operating characteristic analysis. RESULTS: Relative CBV best differentiated meningioma from glioblastoma and from metastasis with areas under the curve of 0.84 and 0.82, respectively. The percentage signal recovery best differentiated primary central nervous system lymphoma from metastasis with an area under the curve of 0.81. Relative CBV and percentage signal recovery were similar in differentiating primary central nervous system lymphoma from glioblastoma and from meningioma. Although neither relative CBV nor percentage signal recovery differentiated glioblastoma from metastasis, mean normalized baseline signal intensity achieved 86% sensitivity and 50% specificity. CONCLUSIONS: Similar to results for non-preload-based DSC-MR imaging, percentage signal recovery for one-quarter-dose preload-based, intermediate flip angle DSC-MR imaging differentiates most pair-wise comparisons of glioblastoma, metastasis, primary central nervous system lymphoma, and meningioma, except for glioblastoma versus metastasis. Differences in normalized post-preload baseline signal for glioblastoma and metastasis, reflecting a snapshot of dynamic contrast enhancement, may motivate the use of single-dose multiecho protocols permitting simultaneous quantification of DSC-MR imaging and dynamic contrast-enhanced MR imaging parameters.

Dismantling the ability of CT and MRI to identify the target mismatch profile in patients with anterior circulation large vessel occlusion beyond six hours from symptom onset.

PURPOSE: Patients with large vessel occlusion and target mismatch on imaging may be thrombectomy candidates in the extended time window. However, the ability of imaging modalities including non-contrast CT Alberta Stroke Program Early Computed Tomographic Scoring (CT ASPECTS), CT angiography collateral score (CTA-CS), diffusion-weighted MRI ASPECTS (DWI ASPECTS), DWI lesion volume, and DWI volume with clinical deficit (DWI + NIHSS), to identify mismatch is unknown. METHODS: We defined target mismatch as core infarct (DWI volume) of < 70 mL, mismatch volume (tissue with TMax > 6 s) of ≥ 15 mL, and mismatch ratio of ≥ 1.8. Using experimental dismantling design, ability to identify this profile was determined for each imaging modality independently (phase 1) and then with knowledge from preceding modalities (phase 2). We used a generalized mixed model assuming binary distribution with PROC GLIMMIX/SAS for analysis. RESULTS: We identified 32 patients with anterior circulation occlusions, presenting > 6 h from symptom onset, with National Institute of Health Stroke Scale of ≥ 6, who had CT and MR before thrombectomy. Sensitivities for identifying target mismatch increased modestly from 88% for NCCT to 91% with the addition of CTA-CS, and up to 100% for all MR-based modalities. Significant gains in specificity were observed from successive tests (29, 19, and 16% increase for DWI ASPECTS, DWI volume, and DWI + NIHSS, respectively). CONCLUSIONS: The combination of NCCT ASPECTS and CTA-CS has high sensitivity for identifying the target mismatch in the extended time window. However, there are gains in specificity with MRI-based imaging, potentially identifying treatment candidates who may have been excluded based on CT imaging alone.

Moving Toward a Consensus DSC-MRI Protocol: Validation of a Low-Flip Angle Single-Dose Option as a Reference Standard for Brain Tumors.

BACKGROUND AND PURPOSE: DSC-MR imaging using preload, intermediate (60°) flip angle and postprocessing leakage correction has gained traction as a standard methodology. Simulations suggest that DSC-MR imaging with flip angle = 30° and no preload yields relative CBV practically equivalent to the reference standard. This study tested this hypothesis in vivo. MATERIALS AND METHODS: Eighty-four patients with brain lesions were enrolled in this 3-institution study. Forty-three patients satisfied the inclusion criteria. DSC-MR imaging (3T, single-dose gadobutrol, gradient recalled-echo-EPI, TE = 20-35 ms, TR = 1.2-1.63 seconds) was performed twice for each patient, with flip angle = 30°-35° and no preload (P-), which provided preload (P+) for the subsequent intermediate flip angle = 60°. Normalized relative CBV and standardized relative CBV maps were generated, including postprocessing with contrast agent leakage correction (C+) and without (C-) contrast agent leakage correction. Contrast-enhancing lesion volume, mean relative CBV, and contrast-to-noise ratio obtained with 30°/P-/C-, 30°/P-/C+, and 60°/P+/C- were compared with 60°/P+/C+ using the Lin concordance correlation coefficient and Bland-Altman analysis. Equivalence between the 30°/P-/C+ and 60°/P+/C+ protocols and the temporal SNR for the 30°/P- and 60°/P+ DSC-MR imaging data was also determined. RESULTS: Compared with 60°/P+/C+, 30°/P-/C+ had closest mean standardized relative CBV (P = .61), highest Lin concordance correlation coefficient (0.96), and lowest Bland-Altman bias (µ = 1.89), compared with 30°/P-/C- (P = .02, Lin concordance correlation coefficient = 0.59, µ = 14.6) and 60°/P+/C- (P = .03, Lin concordance correlation coefficient = 0.88, µ = -10.1) with no statistical difference in contrast-to-noise ratios across protocols. The normalized relative CBV and standardized relative CBV were statistically equivalent at the 10% level using either the 30°/P-/C+ or 60°/P+/C+ protocols. Temporal SNR was not significantly different for 30°/P- and 60°/P+ (P = .06). CONCLUSIONS: Tumor relative CBV derived from low-flip angle, no-preload DSC-MR imaging with leakage correction is an attractive single-dose alternative to the higher dose reference standard.

Echocardiographic Pulmonary Hypertension Predicts Post-transplantation Renal Allograft Failure.

BACKGROUND: Pulmonary hypertension in the setting of renal transplantation has been associated with early allograft dysfunction and increased mortality, but this relationship has not been extensively studied. METHODS: We performed a retrospective cohort study of adult patients who underwent their first renal transplantation in the years 2003-2009 and had pre-transplantation echocardiograms. Pulmonary hypertension was defined as right ventricular systolic pressure ≥40 mm Hg in the absence of left-sided valvular disease and/or left ventricular ejection fraction ≤50%. Eighty-two of 205 patients (40%) met the inclusion criteria. The relationship between pulmonary hypertension and death-censored allograft failure (hemodialysis dependence or retransplantation) and serum creatinine was assessed with the use of Cox hazard regression and generalized mixed models. RESULTS: The presence of pulmonary hypertension was associated with a 3-fold increase in the risk of death-censored allograft failure (95% confidence interval, 1.20-7.32; P = .02). Failure rates were 19% at 24 months and 51% at 96 months for those with pulmonary hypertension versus 7% at 24 months and 20% at 86 months for those without pulmonary hypertension (P = .01). Among those without graft failure, there was an increase in creatinine levels after transplantation (P = .01). Effect estimates were unchanged by adjustment for multiple covariates and when pulmonary hypertension was defined as right ventricular systolic pressure ≥36 mm Hg. CONCLUSIONS: Pulmonary hypertension before renal transplantation carries a 3-fold increased risk of death-censored allograft failure. The relationship between the pulmonary circulation and renal allograft failure warrants further study.

Bladder and bowel continence in bilateral cerebral palsy: A population study.

INTRODUCTION: The attainment of continence is an important milestone in all children, including those with disability. OBJECTIVE: To describe the age of bladder and bowel continence in children with bilateral cerebral palsy (BCP), and the association with intellectual impairment (II) and severity of motor disability. PATIENTS AND METHODS: The parents of 346 children with BCP were interviewed as part of a population-based prospective study of the children at 3, 7, and 17 years of age. The age of bladder and bowel continence by day and night was ascertained and compared with controls from the Avon Longitudinal Study of Parents and Children (ALSPAC). RESULTS: The median age for daytime bladder and bowel continence in BCP children was 5.4 years compared with 2.4 years in the controls. At 13.8 years of age, 59.4% of BCP children and 99% of controls were continent by day. In BCP children, there was no difference between the attainment of daytime bladder and bowel control. Night-time bladder and bowel control was slower and less completely attained, with 50% of BCP children continent by the age of 11.8 years compared with 3 years in control children. At 13.8 years of age, 51.9% of BCP children compared with 99.4% of controls were continent for bowel and bladder at night. Gross Motor Functional Classification Score (GMFCS) and intellectual ability (IA) (II) were strongly associated with continence attainment (P < 0.0001), but gender was not. DISCUSSION: Delayed and less complete continence attainment was noted in other clinic series of children with cerebral palsy (including hemiplegics) and children with II. Severity of motor disability (GMFCS), and II impacted on other aspects of toilet training, such as: motivation, understanding, communication, and independence skills. The presence of neurogenic bladder and bowel dysfunction can occur in all levels of GMFCS. Thus, there are many reasons that can prevent continence attainment. CONCLUSIONS: Children with BCP achieved day and night-time bladder and bowel continence more slowly and less completely than controls, with 60.8% being continent by day and 54.6% by night at the age of 17 years. The majority of BCP children who were continent by day had achieved this by the age of 5.5 years (86%). At least 88% of BCP children with GMFCS I/II and normal, specific or mild learning impairment were continent for bladder and bowel by day and night. Expectations should be shared with parents, and failure to attain expected continence should be actively investigated.

Comparison of parental estimate of developmental age with measured IQ in children with neurodevelopmental disorders.

BACKGROUND: Formal IQ tests are an important part of the diagnostic and needs-based assessment process for children with neurodevelopmental disorders. However, resources for such assessments are not always available. It has been suggested that parental estimates of their child's developmental age could serve as a proxy IQ when formal measures are unavailable. METHOD: Parental estimates of their child's developmental age were converted to a developmental quotient (DQ) in 197 children with Autism Spectrum Disorder (ASD) aged 4-9 years, and 108 children with ADHD and intellectual disability (ADHD + ID) aged 7-15 years. Formal IQ assessments were then conducted. Parents completed the Social Communication Questionnaire ((SCQ), a measure of autism symptomatology) and a demographic questionnaire. RESULTS: In the ASD sample, 58% of parent estimates were within 15 points (i.e. one standard deviation) of the child's measured IQ score. Lower measured IQ and lower SCQ total score predicted higher parental accuracy. In the ADHD + ID sample, 74% of parental estimates were within 15 points of measured IQ. In this group, higher child IQ predicted greater parental accuracy. Parents in the ADHD + ID group were more likely to overestimate children's ability level than parents in the ASD group. CONCLUSIONS: In this study, the majority of parents of children with ADHD and ID were able to estimate their child's intellectual ability level with some accuracy. Parents of children with ASD were less accurate, but this may be because these parents were focussing more on children's level of adaptive functioning, which is known to be typically lower than cognitive ability in ASD.

Elephants in Pyjamas: Testing the Weak Central Coherence Account of Autism Spectrum Disorders Using a Syntactic Disambiguation Task.

According to the weak central coherence (CC) account individuals with autism spectrum disorders (ASD) exhibit enhanced local processing and weak part-whole integration. CC was investigated in the verbal domain. Adolescents, recruited using a 2 (ASD status) by 2 (language impairment status) design, completed an aural forced choice comprehension task involving syntactically ambiguous sentences. Half the picture targets depicted the least plausible interpretation, resulting in longer RTs across groups. These were assumed to reflect local processing. There was no ASD by plausibility interaction and consequently little evidence for weak CC in the verbal domain when conceptualised as enhanced local processing. Furthermore, there was little evidence that the processing of syntactically ambiguous sentences differed as a function of ASD or language-impairment status.

CT colonography at low tube potential: using iterative reconstruction to decrease noise.

AIM: To determine the level of iterative reconstruction required to reduce increased image noise associated with low tube potential computed tomography (CT). MATERIALS AND METHODS: Fifty patients underwent CT colonography with a supine scan at 120 kVp and a prone scan at 100 kVp with other scan parameters unchanged. Both scans were reconstructed with filtered back projection (FBP) and increasing levels of adaptive statistical iterative reconstruction (ASiR) at 30%, 60%, and 90%. Mean noise, soft tissue and tagged fluid attenuation, contrast, and contrast-to-noise ratio (CNR) were collected from reconstructions at both 120 and 100 kVp and compared using a generalised linear mixed model. RESULTS: Decreasing tube potential from 120 to 100 kVp significantly increased image noise by 30-34% and tagged fluid attenuation by 120 HU at all ASiR levels (p<0.0001, all measures). Increasing ASiR from 0% (FBP) to 30%, 60%, and 90% resulted in significant decreases in noise and increases in CNR at both tube potentials (p<0.001, all comparisons). Compared to 120 kVp FBP, ASiR greater than 30% at 100 kVp yielded similar or lower image noise. CONCLUSIONS: Iterative reconstruction adequately compensates for increased image noise associated with low tube potential imaging while improving CNR. An ASiR level of approximately 50% at 100 kVp yields similar noise to 120 kVp without ASiR.

Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment.

Specific language impairment (SLI) is a neurodevelopmental disorder that affects linguistic abilities when development is otherwise normal. We report the results of a genome-wide association study of SLI which included parent-of-origin effects and child genotype effects and used 278 families of language-impaired children. The child genotype effects analysis did not identify significant associations. We found genome-wide significant paternal parent-of-origin effects on chromosome 14q12 (P = 3.74 × 10(-8)) and suggestive maternal parent-of-origin effects on chromosome 5p13 (P = 1.16 × 10(-7)). A subsequent targeted association of six single-nucleotide-polymorphisms (SNPs) on chromosome 5 in 313 language-impaired individuals and their mothers from the ALSPAC cohort replicated the maternal effects, albeit in the opposite direction (P = 0.001); as fathers' genotypes were not available in the ALSPAC study, the replication analysis did not include paternal parent-of-origin effects. The paternally-associated SNP on chromosome 14 yields a non-synonymous coding change within the NOP9 gene. This gene encodes an RNA-binding protein that has been reported to be significantly dysregulated in individuals with schizophrenia. The region of maternal association on chromosome 5 falls between the PTGER4 and DAB2 genes, in a region previously implicated in autism and ADHD. The top SNP in this association locus is a potential expression QTL of ARHGEF19 (also called WGEF) on chromosome 1. Members of this protein family have been implicated in intellectual disability. In summary, this study implicates parent-of-origin effects in language impairment, and adds an interesting new dimension to the emerging picture of shared genetic etiology across various neurodevelopmental disorders.

Speech, communication and use of augmentative communication in young people with cerebral palsy: the SH&PE population study.

BACKGROUND: Communication is frequently impaired in young people (YP) with bilateral cerebral palsy (CP). Important factors include motoric speech problems (dysarthria) and intellectual disability. Augmentative and Alternative Communication (AAC) techniques are often employed. The aim was to describe the speech problems in bilateral CP, factors associated with speech problems, current AAC provision and use, and to explore the views of both the parent/carer and young person about communication. METHODS: A total population of children with bilateral CP (n = 346) from four consecutive years of births (1989-1992 inclusive) with onset of CP before 15 months were reassessed at age 16-18 years. Motor skills and speech were directly assessed and both parent/carer and the young person asked about communication and satisfaction with it. RESULTS: Sixty had died, eight had other conditions, 243 consented and speech was assessed in 224 of whom 141 (63%) had impaired speech. Fifty-two (23% of total YP) were mainly intelligible to unfamiliar people, 22 (10%) were mostly unintelligible to unfamiliar people, 67 (30%) were mostly or wholly unintelligible even to familiar adults. However, 89% of parent/carers said that they could communicate 1:1 with their young person. Of the 128 YP who could independently complete the questions, 107 (83.6%) were happy with their communication, nine (7%) neither happy nor unhappy and 12 (9.4%) unhappy. A total of 72 of 224 (32%) were provided with one or more types of AAC but in a significant number (75% of 52 recorded) AAC was not used at home, only in school. Factors associated with speech impairment were severity of physical impairment, as measured by Gross Motor Function Scale level and manipulation in the best hand, intellectual disability and current epilepsy. CONCLUSIONS: In a population representative group of YP, aged 16-18 years, with bilateral CP, 63% had impaired speech of varying severity, most had been provided with AAC but few used it at home for communication.

Hepatogenous photosensitisation in Scottish sheep casued by Dicrocoelium dendriticum.

Dicrocoeliosis was identified as the probable predisposing cause of weight loss and hepatogenous photosensitisation affecting half of a group of 14 month-old ewe lambs on a farm on the Inner Hebridean island of Coll. Oral dosing of the ewe lambs with 15 mg/kg albendazole only achieved a 79.2% reduction in Dicrocoelium dendriticum egg count, 21 day post treatment. Thus, this report of dicrocoeliosis differs from the disease that occurs elsewhere, both in the severity and nature of its clinical signs, and in the response of the parasite to anthelmintic drug treatment. These differences could indicate the existence of a genetically divergent D. dendriticum population, which may have evolved within the unique and isolated biotope afforded by the machair on the island of Coll. Better understanding of these factors is a prerequisite for effective and sustainable disease control.

The long-term function of the knee in patients with fibular hemimelia and anterior cruciate ligament deficiency.

Most patients (95%) with fibular hemimelia have an absent anterior cruciate ligament (ACL). The purpose of this study was to assess the long-term outcome of such patients with respect to pain and knee function. We performed a retrospective review of patients with fibular hemimelia and associated ACL deficiency previously treated at our institution. Of a possible 66 patients, 23 were sent the Musculoskeletal Outcomes Data Evaluation and Management System (MODEMS) questionnaire and Lysholm knee score to complete. In all, 11 patients completed the MODEMS and nine completed the Lysholm score questionnaire. Their mean age was 37 years (27 to 57) at review. Five patients had undergone an ipsilateral Symes amputation. There was no significant difference in any subsections of the Short-Form 36 scores of our patients compared with age-matched controls. The mean Lysholm knee score was 90.2 (82 to 100). A slight limp was reported in six patients. No patients had episodes of locking of the knee or required a supportive device for walking. Four had occasional instability with sporting activities. These results suggest that patients with fibular hemimelia and ACL deficiency can live active lives with a similar health status to age-matched controls.

Ensuring successful admission to hospital for young people with learning difficulties, autism and challenging behaviour: a continuous quality improvement and change management programme.

BACKGROUND: Children and young people with autism spectrum conditions frequently have adverse experiences in accessing health care. METHODS: An audit of experiences of families known to our tertiary service and hospital staff was conducted. A checklist asking about particular aspects of behaviour and communication was developed and incorporated into pre-admission planning. RESULTS: Awareness of the child/young person's communication needs and behaviours, plus good preplanning by all staff involved and a team member allocated to ensure that the care plan is carried through, has resulted in a vastly improved 'patient experience' from the perspective of family and staff. CONCLUSION: Children and young people with autism spectrum disorder, often with co-existing learning difficulties, vary greatly in their reactions to hospital admission. Preplanning that involves the family with a dedicated informed staff member can dramatically reduce distress and improve the patient and staff experience.

IQ in children with autism spectrum disorders: data from the Special Needs and Autism Project (SNAP).

BACKGROUND: Autism spectrum disorder (ASD) was once considered to be highly associated with intellectual disability and to show a characteristic IQ profile, with strengths in performance over verbal abilities and a distinctive pattern of 'peaks' and 'troughs' at the subtest level. However, there are few data from epidemiological studies. METHOD: Comprehensive clinical assessments were conducted with 156 children aged 10-14 years [mean (s.d.)=11.7 (0.9)], seen as part of an epidemiological study (81 childhood autism, 75 other ASD). A sample weighting procedure enabled us to estimate characteristics of the total ASD population. RESULTS: Of the 75 children with ASD, 55% had an intellectual disability (IQ<70) but only 16% had moderate to severe intellectual disability (IQ<50); 28% had average intelligence (115>IQ>85) but only 3% were of above average intelligence (IQ>115). There was some evidence for a clinically significant Performance/Verbal IQ (PIQ/VIQ) discrepancy but discrepant verbal versus performance skills were not associated with a particular pattern of symptoms, as has been reported previously. There was mixed evidence of a characteristic subtest profile: whereas some previously reported patterns were supported (e.g. poor Comprehension), others were not (e.g. no 'peak' in Block Design). Adaptive skills were significantly lower than IQ and were associated with severity of early social impairment and also IQ. CONCLUSIONS: In this epidemiological sample, ASD was less strongly associated with intellectual disability than traditionally held and there was only limited evidence of a distinctive IQ profile. Adaptive outcome was significantly impaired even for those children of average intelligence.

Defining the cognitive phenotype of autism.

Although much progress has been made in determining the cognitive profile of strengths and weaknesses that characterise individuals with autism spectrum disorders (ASDs), there remain a number of outstanding questions. These include how universal strengths and deficits are; whether cognitive subgroups exist; and how cognition is associated with core autistic behaviours, as well as associated psychopathology. Several methodological factors have contributed to these limitations in our knowledge, including: small sample sizes, a focus on single domains of cognition, and an absence of comprehensive behavioural phenotypic information. To attempt to overcome some of these limitations, we assessed a wide range of cognitive domains in a large sample (N=100) of 14- to 16-year-old adolescents with ASDs who had been rigorously behaviourally characterised. In this review, we will use examples of some initial findings in the domains of perceptual processing, emotion processing and memory, both to outline different approaches we have taken to data analysis and to highlight the considerable challenges to better defining the cognitive phenotype(s) of ASDs. Enhanced knowledge of the cognitive phenotype may contribute to our understanding of the complex links between genes, brain and behaviour, as well as inform approaches to remediation.

Autism spectrum disorder diagnostic assessments: improvements since publication of the National Autism Plan for Children.

OBJECTIVES: To assess in the context of a publically funded healthcare system, change in UK autism spectrum disorder (ASD) clinical diagnostic practice following the recommendations of the National Autism Plan for Children (NAP-C 2003). METHODS: In 2007, a questionnaire based on standards from the NAP-C was sent to UK child development teams (CDTs); results were compared with 2001 data from the National Initiative for Autism Screening and Assessment. MAIN FINDINGS: Responses were received from 149 of 243 UK CDTs (61%). Most teams used standardised autism diagnostic assessments. There was greater access to members of the multidisciplinary team than in 2001. Only one-third of teams had a defined timescale for completion of assessment; of those teams, about half met the recommended NAP-C target. CONCLUSIONS: Since 2001, there has been an improvement in diagnostic services for children with ASD, however, inequalities remain. Providers should continue to improve services in order to deliver timely and comprehensive assessments for children with ASD.

Non-word repetition in adolescents with specific language impairment and autism plus language impairments: a qualitative analysis.

UNLABELLED: Non-word repetition (NWR) was investigated in adolescents with typical development, Specific Language Impairment (SLI) and Autism Plus language Impairment (ALI) (n=17, 13, 16, and mean age 14;4, 15;4, 14;8 respectively). The study evaluated the hypothesis that poor NWR performance in both groups indicates an overlapping language phenotype (Kjelgaard & Tager-Flusberg, 2001). Performance was investigated both quantitatively, e.g. overall error rates, and qualitatively, e.g. effect of length on repetition, proportion of errors affecting phonological structure, and proportion of consonant substitutions involving manner changes. Findings were consistent with previous research (Whitehouse, Barry, & Bishop, 2008) demonstrating a greater effect of length in the SLI group than the ALI group, which may be due to greater short-term memory limitations. In addition, an automated count of phoneme errors identified poorer performance in the SLI group than the ALI group. These findings indicate differences in the language profiles of individuals with SLI and ALI, but do not rule out a partial overlap. Errors affecting phonological structure were relatively frequent, accounting for around 40% of phonemic errors, but less frequent than straight Consonant-for-Consonant or vowel-for-vowel substitutions. It is proposed that these two different types of errors may reflect separate contributory mechanisms. Around 50% of consonant substitutions in the clinical groups involved manner changes, suggesting poor auditory-perceptual encoding. From a clinical perspective algorithms which automatically count phoneme errors may enhance sensitivity of NWR as a diagnostic marker of language impairment. LEARNING OUTCOMES: Readers will be able to (1) describe and evaluate the hypothesis that there is a phenotypic overlap between SLI and Autism Spectrum Disorders (2) describe differences in the NWR performance of adolescents with SLI and ALI, and discuss whether these differences support or refute the phenotypic overlap hypothesis, and (3) understand how computational algorithms such as the Levenshtein Distance may be used to analyse NWR data.

Control of caseous lymphadenitis in six sheep flocks using clinical examination and regular ELISA testing.

In an effort to control the spread of caseous lymphadenitis (CLA) infection, flocks of affected sheep on six holdings were tested serologically at regular intervals using an antibody ELISA with a mean (sd) specificity of 99 (1) per cent and a sensitivity of 79 (5) per cent. Western blot assays to detect antibodies to the phospholipase D (PLD) exotoxin of Corynebacterium pseudotuberculosis were used as a further test when ELISA results were inconclusive. Owners were advised to remove from the flock any sheep that demonstrated clinical signs of CLA or tested positive for PLD by ELISA or western blot. Of the six trial flocks, one was dispersed after only two blood tests, and in another the recommendations for CLA control were not followed and infected animals were retained within the flock. In the remaining four flocks, the testing regimen and other advice enabled the disease to be controlled to such an extent that the appearance of new clinical cases of CLA was effectively halted. This remained the case for up to five years after the end of the trial. In two of these flocks, a small number of seropositive animals were detected at the last flock test). However, on the other two holdings all sheep were seronegative in the final two flock tests, consistent with the complete eradication of infection.