Generalized models for quantifying laterality using functional transcranial Doppler ultrasound.

We consider how analysis of brain lateralization using functional transcranial Doppler ultrasound (fTCD) data can be brought in line with modern statistical methods typically used in functional magnetic resonance imaging (fMRI). Conventionally, a laterality index is computed in fTCD from the difference between the averages of each hemisphere's signal within a period of interest (POI) over a series of trials. We demonstrate use of generalized linear models (GLMs) and generalized additive models (GAM) to analyze data from individual participants in three published studies (N = 154, 73 and 31), and compare this with results from the conventional POI averaging approach, and with laterality assessed using fMRI (N = 31). The GLM approach was based on classic fMRI analysis that includes a hemodynamic response function as a predictor; the GAM approach estimated the response function from the data, including a term for time relative to epoch start (simple GAM), plus a categorical index corresponding to individual epochs (complex GAM). Individual estimates of the fTCD laterality index are similar across all methods, but error of measurement is lowest using complex GAM. Reliable identification of cases of bilateral language appears to be more accurate with complex GAM. We also show that the GAM-based approach can be used to efficiently analyze more complex designs that incorporate interactions between tasks.

Mapping and identifying service models for community-based services for children with intellectual disabilities and behaviours that challenge in England.

BACKGROUND: One in five children with an intellectual disability in the UK display behaviours that challenge. Despite associated impacts on the children themselves, their families, and services, little research has been published about how best to design, organise, and deliver health and care services to these children. The purpose of this study was to describe how services are structured and organised ("service models") in England for community-based health and care services for children with intellectual disability who display behaviours that challenge. METHODS: Survey data about services were collected from 161 eligible community-based services in England. Staff from 60 of these services were also interviewed. A combination of latent class and descriptive analysis, coupled with consultation with family carers and professionals was used to identify and describe groupings of similar services (i.e., "service models"). RESULTS: The latent class analysis, completed as a first step in the process, supported a distinction between specialist services and non-specialist services for children who display behaviours that challenge. Planned descriptive analyses incorporating additional study variables were undertaken to further refine the service models. Five service models were identified: Child and Adolescent Mental Health Services (CAMHS) (n = 69 services), Intellectual Disability CAMHS (n = 28 services), Children and Young People Disability services (n = 25 services), Specialist services for children who display behaviours that challenge (n = 27 services), and broader age range services for children and/or adolescents and adults (n= 12 services). CONCLUSIONS: Our analysis led to a typology of five service models for community health and care services for children with intellectual disabilities and behaviours that challenge in England. Identification of a typology of service models is a first step in building evidence about the best provision of services for children with intellectual disabilities who display behaviours that challenge. The methods used in the current study may be useful in research developing service typologies in other specialist fields of health and care. STUDY REGISTRATION: Trial Registration: Current Controlled Trials ISRCTN88920546, Date assigned 05/07/2022.

Psychiatric inpatient admissions and discharges of people with intellectual disabilities: A time series analysis of English national data.

BACKGROUND: We examined whether a series of variables were related to the number of psychiatric inpatients using publicly available data about English psychiatric bed utilisation and NHS workforce. METHOD: Using linear regression, with auto-regressive errors, we examined relationships between variables over time using data from December 2013 to March 2021. RESULTS: Over time, the number of inpatients reduced by either 6.58 or 8.07 per month depending upon the dataset utilised, and the number of community nurses and community nursing support staff reduced by 7.43 and 2.14 nurses per month, respectively. Increasing numbers of consultant psychiatrists were associated with fewer inpatients over time. More care and treatment reviews (CTRs) were associated with more admissions over time, while more post-admission CTRs were associated with increased discharges over time. CONCLUSIONS: Future studies should examine whether psychiatric bed utilisation elsewhere within the NHS by people with intellectual disabilities has increased.

Functional organisation for verb generation in children with developmental language disorder.

Developmental language disorder (DLD) is characterised by difficulties in learning one's native language for no apparent reason. These language difficulties occur in 7% of children and are known to limit future academic and social achievement. Our understanding of the brain abnormalities associated with DLD is limited. Here, we used a simple four-minute verb generation task (children saw a picture of an object and were instructed to say an action that goes with that object) to test children between the ages of 10-15 years (DLD N = 50, typically developing N = 67). We also tested 26 children with poor language ability who did not meet our criteria for DLD. Contrary to our registered predictions, we found that children with DLD did not have (i) reduced activity in language relevant regions such as the left inferior frontal cortex; (ii) dysfunctional striatal activity during overt production; or (iii) a reduction in left-lateralised activity in frontal cortex. Indeed, performance of this simple language task evoked activity in children with DLD in the same regions and to a similar level as in typically developing children. Consistent with previous reports, we found sub-threshold group differences in the left inferior frontal gyrus and caudate nuclei, but only when analysis was limited to a subsample of the DLD group (N = 14) who had the poorest performance on the task. Additionally, we used a two-factor model to capture variation in all children studied (N = 143) on a range of neuropsychological tests and found that these language and verbal memory factors correlated with activity in different brain regions. Our findings indicate a lack of support for some neurological models of atypical language learning, such as the procedural deficit hypothesis or the atypical lateralization hypothesis, at least when using simple language tasks that children can perform. These results also emphasise the importance of controlling for and monitoring task performance.

Profile of language abilities in a sample of adults with developmental disorders.

This study investigated the profile of language abilities in a sample of high-achieving English speaking adults with developmental disorders. Ninety-seven adult participants were recruited: 49 with a dyslexia diagnosis (dyslexic group), 16 with a diagnosis of a different developmental disorder including dyspraxia, autism and SpLD (non-dyslexic developmental disorder group) and 32 with no diagnosis (non-disordered group). Dyslexic and non-dyslexic developmental disorder groups demonstrated similar impairments across measures of word reading, working memory, processing speed and oral language. Dyslexic participants showed the usual pattern of impaired phonological skills but spared non-verbal intelligence and vocabulary. There were also some suggestions of impaired structural oral language skills in this group. A data-driven clustering analysis found that diagnosis was not a reliable predictor of similarity between cases, with diagnostic categories split between data-driven clusters. Overall, the findings indicate that high-achieving adults with developmental disorders do demonstrate impairments that are likely to affect success in higher education, but that support needs should be assessed on a case-by-case basis, rather than according to diagnostic label.

Assessing the reliability of an online behavioural laterality battery: A pre-registered study.

Studies of cerebral lateralization often involve participants completing a series of perceptual tasks under laboratory conditions. This has constrained the number of participants recruited in such studies. Online testing can allow for much larger sample sizes but limits the amount of experimental control that is feasible. Here we considered whether online testing could give valid and reliable results on four tasks: a rhyme decision visual half-field task, a dichotic listening task, a chimeric faces task, and a finger tapping task. We recruited 392 participants, oversampling left-handers, who completed the battery twice. Three of the tasks showed evidence of both validity and reliability, insofar as they showed hemispheric advantages in the expected direction and test-retest reliability of at least r = .75. The reliability of the rhyme decision task was less satisfactory (r = .62). We also confirmed a prediction that extreme left-handers were more likely to depart from typical lateralization. Lateralization across the two language tasks (dichotic listening and rhyme judgement) was weakly correlated, but unrelated to lateralization on the chimeric faces task. We conclude that three of the tasks, dichotic listening, chimeric faces and finger tapping, show considerable promise for online evaluation of cerebral lateralization.

Copy number variation burden does not predict severity of neurodevelopmental phenotype in children with a sex chromosome trisomy.

Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)-stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss-of-function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within-group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems.

Investigation into inconsistent lateralisation of language functions as a potential risk factor for language impairment.

Disruption to language lateralisation has been proposed as a cause of developmental language impairments. In this study, we tested the idea that consistency of lateralisation across different language functions is associated with language ability. A large sample of adults with variable language abilities (N = 67 with a developmental disorder affecting language and N = 37 controls) were recruited. Lateralisation was measured using functional transcranial Doppler sonography (fTCD) for three language tasks that engage different language subprocesses (phonological decision, semantic decision and sentence generation). The whole sample was divided into those with consistent versus inconsistent lateralisation across the three tasks. Language ability (using a battery of standardised tests) was compared between the consistent and inconsistent groups. The results did not show a significant effect of lateralisation consistency on language skills. However, of the 31 individuals showing inconsistent lateralisation, the vast majority (84%) were in the disorder group with only five controls showing such a pattern, a difference that was higher than would be expected by chance. The developmental disorder group also demonstrated weaker correlations between laterality indices across pairs of tasks. In summary, although the data did not support the hypothesis that inconsistent language lateralisation is a major cause of poor language skills, the results suggested that some subtypes of language disorder are associated with inefficient distribution of language functions between hemispheres. Inconsistent lateralisation could be a causal factor in the aetiology of language disorder or may arise in some cases as the consequence of developmental disorder, possibly reflective of compensatory reorganisation.

Logical and Methodological Issues Affecting Genetic Studies of Humans Reported in Top Neuroscience Journals.

Genetics and neuroscience are two areas of science that pose particular methodological problems because they involve detecting weak signals (i.e., small effects) in noisy data. In recent years, increasing numbers of studies have attempted to bridge these disciplines by looking for genetic factors associated with individual differences in behavior, cognition, and brain structure or function. However, different methodological approaches to guarding against false positives have evolved in the two disciplines. To explore methodological issues affecting neurogenetic studies, we conducted an in-depth analysis of 30 consecutive articles in 12 top neuroscience journals that reported on genetic associations in nonclinical human samples. It was often difficult to estimate effect sizes in neuroimaging paradigms. Where effect sizes could be calculated, the studies reporting the largest effect sizes tended to have two features: (i) they had the smallest samples and were generally underpowered to detect genetic effects, and (ii) they did not fully correct for multiple comparisons. Furthermore, only a minority of studies used statistical methods for multiple comparisons that took into account correlations between phenotypes or genotypes, and only nine studies included a replication sample or explicitly set out to replicate a prior finding. Finally, presentation of methodological information was not standardized and was often distributed across Methods sections and Supplementary Material, making it challenging to assemble basic information from many studies. Space limits imposed by journals could mean that highly complex statistical methods were described in only a superficial fashion. In summary, methods that have become standard in the genetics literature-stringent statistical standards, use of large samples, and replication of findings-are not always adopted when behavioral, cognitive, or neuroimaging phenotypes are used, leading to an increased risk of false-positive findings. Studies need to correct not just for the number of phenotypes collected but also for the number of genotypes examined, genetic models tested, and subsamples investigated. The field would benefit from more widespread use of methods that take into account correlations between the factors corrected for, such as spectral decomposition, or permutation approaches. Replication should become standard practice; this, together with the need for larger sample sizes, will entail greater emphasis on collaboration between research groups. We conclude with some specific suggestions for standardized reporting in this area.

Clinical factors associated with physician choice of femoral versus radial access: A real-world experience from a single academic center.

OBJECTIVES: To analyze clinical factors associated with operator's preference in selection of femoral versus radial access for angiography and percutaneous intervention (PCI) procedures. BACKGROUND: There has been an increase in radial access in cardiac catheterization and PCI in the last few decades. METHODS: Data from 11 226 consecutive cardiac catheterization procedures were collected from Sanford University Medical Center (University of South Dakota, Sanford School of Medicine) from 2011 to 2015. RESULTS: In the overall cases, clinical factors that favored upfront femoral access include patients presenting as ST-elevation myocardial infarction (STEMI) or emergent, coronary artery bypass graft, body mass index (BMI) <30 kg/m2 and age ≥70 years, whereas morbidly obese patients (BMI ≥35) and age <70 favored upfront radial access. Radial access in the overall group had lower fluoroscopy time (6.5 vs 8.4 min, P < 0.0001) and lower contrast use (68.8 vs 80.6 cc, P < 0.0001). In the PCI group, efficacy of upfront radial access is less evident with radial fluoroscopy time (10.1 vs 11.0 min, P < 0.0028) and contrast use being higher in radial group (113.8 vs 108.2 cc, P < 0.037). Interventional cardiologists were more efficient in diagnostic cases than non-interventional cardiologists. CONCLUSION: STEMI or emergent cases and elderly patients favor upfront femoral access. As BMI increases and age decreases, radial access is progressively favored. In diagnostic cases, radial access appears to be superior to femoral access in efficacy, but the distinction is less obvious in PCI and STEMI or emergent cases.

Evaluation and comparison of staining patterns of factor XIIIa (AC-1A1), adipophilin and GATA3 in sebaceous neoplasia.

BACKGROUND: Reliable nuclear immunohistochemical stains for sebaceous neoplasms have not been readily available. Positive nuclear staining has been reported for GATA3 and factor XIIIa (AC-1A1). We sought to determine the diagnostic utility of these nuclear stains by comparing their staining pattern to adipophilin, a consistently positive cytoplasmic stain. METHODS: Cases with the diagnosis of sebaceous hyperplasia, sebaceous adenoma, sebaceous epithelioma/sebaceoma, sebaceous carcinoma, and nonsebaceous neoplasms (basal cell carcinoma and squamous cell carcinoma) were examined. Intensity and extent of staining of the basal cells and mature sebocytes were evaluated for each stain. RESULTS: Factor XIIIa (AC-1A1) was 87.3% sensitive and 95.1% specific for all sebaceous neoplasms sand showed high inter-observer reliability. Adipophilin was 83.2% sensitive and 87.8% specific. GATA3 was the least sensitive (80.9%) and specific (75.6%) marker. When factor XIIIa was compared against composite staining of all three markers its staining was still uniquely significant (P = .0210). CONCLUSION: Factor XIIIa (AC-1A1) is a sensitive and specific nuclear marker for sebaceous differentiation. Its diagnostic utility exceeds that of adipophilin. Factor XIIIa should be included in the expanding group of immunohistochemical and special stains which can be utilized to aid in the diagnosis of sebaceous neoplasms.

Growth in syntactic complexity between four years and adulthood: evidence from a narrative task.

Studies examining productive syntax have used varying elicitation methods and have tended to focus on either young children or adolescents/adults, so we lack an account of syntactic development throughout middle childhood. We describe here the results of an analysis of clause complexity in narratives produced by 354 speakers aged from four years to adulthood using the Expressive, Receptive, and Recall of Narrative Instrument (ERRNI). We show that the number of clauses per utterance increased steadily through this age range. However, the distribution of clause types depended on which of two stories was narrated, even though both stories were designed to have a similar story structure. In addition, clausal complexity was remarkably similar regardless of whether the speaker described a narrative from pictures, or whether the same narrative was recalled from memory. Finally, our findings with the youngest children showed that the task of generating a narrative from pictures may underestimate syntactic competence in those aged below five years.

The Collaborative Laborist and Midwifery Model: An Accepted and Sustainable Model.

In 2010, the OB/GYN physicians at this mid-sized midwestern medical center implemented a laborist model on the obstetrics ward. A laborist is a dedicated obstetrician within the obstetric ward who oversees the management of labor and performs deliveries as both the primary physician and also when consulted by other providers, including community obstetricians, family physicians and nurse midwives. In 2014, a collaborative obstetric model was implemented with the addition of an in-house certified nurse midwife (CNM) to assist the laborist in obstetric care. This retrospective study analyzes the impact of these care models on clinical outcomes, including rates of induction of labor, total (primary and repeat) cesarean sections, and vaginal births after cesarean section. The three time periods (i.e., pre-laborist, laborist, laborist plus CNM) periods are compared. Induction rates decreased from 48.6 percent to 46.5 percent to 28.8 percent during the three time periods. Primary cesarean section rates decreased from 15.9 percent to 14.6 percent to 13.6 percent. Total cesarean section rates slightly decreased but this was not statistically significant, going from 28.9 percent to 28.4 percent, to 27.7 percent. Vaginal births after cesarean section increased from 9.2 percent to 12.9 percent to 15 percent. Staff satisfaction was also measured utilizing anonymous surveys during the first two time periods. There was improvement in seven of the eight questions from the pre-laborist to the laborist model. In conclusion, a collaborative care model on the obstetric floor at this Institution has had a positive impact on patient care outcomes and staff satisfaction.

Phase 2 of CATALISE: a multinational and multidisciplinary Delphi consensus study of problems with language development: Terminology.

BACKGROUND: Lack of agreement about criteria and terminology for children's language problems affects access to services as well as hindering research and practice. We report the second phase of a study using an online Delphi method to address these issues. In the first phase, we focused on criteria for language disorder. Here we consider terminology. METHODS: The Delphi method is an iterative process in which an initial set of statements is rated by a panel of experts, who then have the opportunity to view anonymised ratings from other panel members. On this basis they can either revise their views or make a case for their position. The statements are then revised based on panel feedback, and again rated by and commented on by the panel. In this study, feedback from a second round was used to prepare a final set of statements in narrative form. The panel included 57 individuals representing a range of professions and nationalities. RESULTS: We achieved at least 78% agreement for 19 of 21 statements within two rounds of ratings. These were collapsed into 12 statements for the final consensus reported here. The term 'Language Disorder' is recommended to refer to a profile of difficulties that causes functional impairment in everyday life and is associated with poor prognosis. The term, 'Developmental Language Disorder' (DLD) was endorsed for use when the language disorder was not associated with a known biomedical aetiology. It was also agreed that (a) presence of risk factors (neurobiological or environmental) does not preclude a diagnosis of DLD, (b) DLD can co-occur with other neurodevelopmental disorders (e.g. ADHD) and (c) DLD does not require a mismatch between verbal and nonverbal ability. CONCLUSIONS: This Delphi exercise highlights reasons for disagreements about terminology for language disorders and proposes standard definitions and nomenclature.

Analysis of Reimbursement of Genetic Counseling Services at a Single Institution in a State Requiring Licensure.

Reimbursement for genetic counseling services was examined at a single institution. Patient encounters utilizing the 96040 CPT® code from 7/31/2009 through 7/31/2013 were reviewed. Exclusion criteria included billing records of patients seen by a physician the same day, self-pay, Medicaid, and Medicare patients. Of the 8,630 encounters with a genetic counselor, 582 encounters were eligible for review. Descriptive statistics (i.e., percentage of encounters receiving some level of reimbursement, average reimbursement rate, number of third party payors providing any level of reimbursement, and number of ICD-9 codes receiving any level of reimbursement) depicted reimbursement of the 96040 CPT® code for the encounters analyzed. Statistical analysis found a significant difference in reimbursement between third party payors that do and do not credential genetic counselors (p < .0001). There was no statistically significant difference between reimbursement rates for primary diagnostic ICD-9 codes when compared to primary diagnostic ICD-9 V codes used. Results will provide a useful baseline for local and national comparisons due to the paucity of data regarding CPT® 96040.

Precursors of Reading Difficulties in Czech and Slovak Children At-Risk of Dyslexia.

Children with preschool language difficulties are at high risk of literacy problems; however, the nature of the relationship between delayed language development and dyslexia is not understood. Three hundred eight Slovak and Czech children were recruited into three groups: family risk of dyslexia, speech/language difficulties and controls, and were assessed three times from kindergarten until Grade 1. There was a twofold increase in probability of reading problems in each risk group. Precursors of 'dyslexia' included difficulties in oral language and code-related skills (phoneme awareness, letter-knowledge and rapid automatized naming); poor performance in phonological memory and vocabulary was observed in both affected and unaffected high-risk peers. A two-group latent variable path model shows that early language skills predict code-related skills, which in turn predict literacy skills. Findings suggest that dyslexia in Slavic languages has its origins in early language deficits, and children who succumb to reading problems show impaired code-related skills before the onset of formal reading instruction. Copyright © 2016 John Wiley & Sons, Ltd.

Mitral Valve Repair Outcomes in a Community Hospital: A Retrospective Analysis.

BACKGROUND: The results of mitral valve repair operations conducted at community hospitals in rural states are not well studied or reported in the literature. METHODS: We retrospectively assessed consecutive patients who underwent isolated mitral valve repair operations performed by a single experienced cardiothoracic surgeon at a large community hospital from May 1, 2006 - April 30, 2010. Patients were monitored for up to three years (average 2.2 years) following surgery for a variety of surgical variables, including morbidity, mortality, and serial two-dimensional transthoracic echocardiographic findings. Comparisons were made with the Society of Thoracic Surgeons Adult Cardiac Surgery Database (ACSD). RESULTS: Sixty-three consecutive patients underwent isolated complex mitral repair operations. Echocardiographic and morbidity data demonstrated successful outcomes, with no operative mortality and a single cardiac-related death within three years postoperatively. Other variables, especially those that relate to post-repair outcomes, showed no significant differences between our patients and comparison data from the ASCD. CONCLUSIONS: Our study demonstrates equivalent risks and outcomes for complex mitral valve repair performed in a community hospital setting as those found in a national database. The appropriate institutional setting for performing highly complex procedures has substantial implications for health policy, especially regarding access and quality issues.

The Asfora Bullet Cage System Shows Comparable Fusion Rate Success Versus Control Cage in Posterior Lumbar Interbody Fusion in a Randomized Clinical Trial.

BACKGROUND: Low back pain and degeneration of the intervertebral disc are an integrated malady that affects millions of Americans. Cage devices used in association with posterior lumbar interbody fusion (PLIF) have been shown to be an effective approach in the treatment of a number of lower spine disorders attributed to degenerative disc disease (DDD). OBJECTIVE: This study was undertaken as part of a U.S. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) study and compares the effectiveness of the Asfora Bullet Cage System (ABCS) to successfully fuse vertebra at one or two levels between L2 and S1 in patients with DDD to an FDA approved comparison device, the Medtronic-Sofamor Danek Inter Fix Threaded Fusion Device (MSDIFD). METHODS: A total of 257 randomized participants were implanted with either the ABCS device (n = 132) or the MSDIFD device (n = 125) through an open posterior approach using autogenous local bone graft without the use of pedicle screws. Patients were evaluated prior to surgery and at the 24 month (24-M) visit for fusion status, deep tendon reflex status, sensory function, motor function, straight leg raise status, pain, disability, and device safety. Radiological evaluation and statistical analysis were performed by independent professionals. RESULTS: Evaluation of device success was performed at 24-M visit. From the original group of 257 patients, 59 were lost to follow-up. Primary measures of success at the 24-M visit involved pain and function, fusion, neurological status, and device-related adverse events measures. Pain and function improved in both (MSDIFD: 75.7 percent; ABCS: 82.6 percent). Fusion success with all radiographic points at 24-M visits was 79.4 percent MSDIFD and 88.2 percent ABCS. Neurological improvement was seen in both (MSDIFD: 77.0 percent; ABCS: 87.8 percent). One device-related grade 1 adverse event was reported in the MSDIFD group. Disc height preservation was equivalent for single level fusions (MSDIFD: 16.1 percent; ABCS: 20.0 percent) and second level fusions (MSDIFD: 10.7 percent; ABCS: 14.3 percent). General health and well-being improvement was the same (MSDIFD: 37.0 percent; ABCS: 40.0 percent). Subsequent fusion, up to 10 years, was equivalent (MSDIFD: 83.8 percent; ABCS: 91.2). Results for both devices were considered to be satisfactory, with a slight non-significant superiority for the ABCS. CONCLUSION: From the ABCS device FDA IDE sanctioned study and the review of the literature, we concluded that the Asfora Bullet Cage System is safe, effective and comparable to other interbody fusion devices which are used stand-alone or in conjunction with pedicle screws, rhBMP-2, or autogenous bone harvested from the iliac crest inserted through anterior, lateral or posterior approaches.