Understanding chromosome disorders and their implications for special educators

More children are now being diagnosed with chromosome abnormalities. Some chromosome disorder syndromes are relatively well known; while others are so rare that there is only limited evidence about their likely impact on learning and development. For educators, a basic level of knowledge about chromosome abnormalities is important for understanding the literature and communicating with families and professionals. This paper describes chromosomes, and the numerical and structural anomalies that can occur, usually spontaneously during early cell division. Distinctive features of various chromosome syndromes are summarised before a discussion of the rare chromosome disorders that are labelled, not with a syndrome name, but simply by a description of the chromosome number, size and shape. Because of the potential within-group variability that characterises syndromes, and the scarcity of literature about the rare chromosome disorders, expectations for learning and development of individual students need to be based on the range of possible outcomes that may be achievable.

Radiographer commenting of trauma radiographs : a survey of the benefits, barriers and enablers to participation in an Australian healthcare setting

Introduction Radiographer abnormality detection systems that highlight abnormalities on trauma radiographs (‘red dot’ system) have been operating for more than 30 years. Recently, a number of pitfalls have been identified. These limitations initiated the evolution of a radiographer commenting system, whereby a radiographer provides a brief description of abnormalities identified in emergency healthcare settings. This study investigated radiographers' participation in abnormality detection systems, their perceptions of benefits, barriers and enablers to radiographer commenting, and perceptions of potential radiographer image interpretation services for emergency settings. Methods A cross-sectional survey was implemented. Participants included radiographers from four metropolitan hospitals in Queensland, Australia. Conventional descriptive statistics, histograms and thematic analysis were undertaken. Results Seventy-three surveys were completed and included in the analysis (68% response rate); 30 (41%) of respondents reported participating in abnormality detection in 20% or less of examinations, and 26(36%) reported participating in 80% or more of examinations. Five overarching perceived benefits of radiographer commenting were identified: assisting multidisciplinary teams, patient care, radiographer ability, professional benefits and quality of imaging. Frequently reported perceived barriers included ‘difficulty accessing image interpretation education’, ‘lack of time’ and ‘low confidence in interpreting radiographs’. Perceived enablers included ‘access to image interpretation education’ and ‘support from radiologist colleagues’. Conclusions A range of factors are likely to contribute to the successful implementation of radiographer commenting in addition to abnormality detection in emergency settings. Effective image interpretation education amenable to completion by radiographers would likely prove valuable in preparing radiographers for participation in abnormality detection and commenting systems in emergency settings.

Rapid on-site evaluation of fine needle aspiration specimens by cytology scientists : a review of 3032 specimens

Objectives To determine: (1) the accuracy of cytology scientists at assessing specimen adequacy by rapid on-site evaluation (ROSE) at fine needle aspiration (FNA) cytology collections; and (2) whether thyroid FNA with ROSE has lower inadequacy rates than non-attended FNAs. Methods The ROSE of adequacy for 3032 specimens from 17 anatomical sites collected over a 20-month period was compared with the final report assessment of adequacy. ROSE was performed by 19 cytology scientists. The report profile for 1545 thyroid nodules with ROSE was compared with that for 1536 consecutive non-ROSE thyroid FNAs reported by the same cytopathologists during the study period. Results ROSE was adequate in 75% (2276/3032), inadequate in 12% (366/3032) and in 13% (390/3032) no opinion was rendered. Of the 2276 cases assessed as adequate by ROSE, 2268 (99.6%) were finally reported as adequate for assessment; eight specimens had adequacy downgraded on the final report. Fifty eight per cent of cases with a ROSE assessment of inadequate were reported as adequate (212/366), whereas 93% (363/390) with no opinion rendered were reported as adequate. The overall final report adequacy rate for the 3032 specimens was 94% (2843/3032). Confirmation of a ROSE of adequacy at reporting was uniformly high amongst the 19 scientists, ranging from 98% to 100%. The inadequacy rate for thyroid FNAs with ROSE (6%) was significantly (P < 0.0001) lower than for non-ROSE thyroid FNAs (17%). A significantly (P = 0.02) higher proportion of adequate ROSE thyroid specimens was reported with abnormalities, compared with non-ROSE thyroid collections. Conclusions Cytology scientists are highly accurate at determining specimen adequacy at ROSE for a wide range of body sites. ROSE of thyroid FNAs can significantly reduce inadequate reports.

Performance measures for Australian laboratories reporting cervical cytology : a decade of data 1998–2008

Aim Performance measures for Australian laboratories reporting cervical cytology are a set of quantifiable measures relating to the profile and accuracy of reporting. This study reviews aggregate data collected over the ten years in which participation in the performance measures has been mandatory. Methods Laboratories submit annual data on performance measures relating to the profile of reporting, including reporting rates for technically unsatisfactory specimens, high grade or possible high grade abnormalities and abnormal reports. Cytology-histology correlation data and review findings of negative smears reported from women with histological high grade disease are also collected. Suggested acceptable standards are set for each measure. This study reviews the aggregate data submitted by all laboratories for the years 1998-2008 and examines trends in reporting and the performance of laboratories against the suggested standards. Results The performance of Australian laboratories has shown continued improvement over the study period. There has been a fall in the proportion of laboratories with data outside the acceptable standard range in all performance measures. Laboratories are reporting a greater proportion of specimens as definite or possible high grade abnormality. This is partly attributable to an increase in the proportion of abnormal results classified as high grade or possible high grade abnormality. Despite this, the positive predictive value for high grade and possible high grade abnormalities has continued to rise. Conclusion Performance measures for cervical cytology have provided a valuable addition to external quality assurance procedures in Australia. They have documented continued improvements in the aggregate performance, as well as providing benchmarking data and goals for acceptable performance for individual laboratories.

Centrobin regulates the assembly of functional mitotic spindles

The proper function of the spindle is crucial to the high fidelity of chromosome segregation and is indispensable for tumor suppression in humans. Centrobin is a recently identified centrosomal protein that has a role in stabilizing the microtubule structure. Here we functionally characterize the defects in centrosome integrity and spindle assembly in Centrobin-depleted cells. Centrobin-depleted cells show a range of spindle abnormalities including unfocused poles that are not associated with centrosomes, S-shaped spindles and mini spindles. These cells undergo mitotic arrest and subsequently often die by apoptosis, as determined by live cell imaging. Co-depletion of Mad2 relieves the mitotic arrest, indicating that cells arrest due to a failure to silence the spindle checkpoint in metaphase. Consistent with this, Centrobin-depleted metaphase cells stained positive for BubR1 and BubR1 S676. Staining with a panel of centrosome markers showed a loss of centrosome anchoring to the mitotic spindle. Furthermore, these cells show less cold-stable microtubules and a shorter distance between kinetochore pairs. These results show a requirement of Centrobin in maintaining centrosome integrity, which in turn promotes anchoring of mitotic spindle to the centrosomes. Furthermore, this anchoring is required for the stability of microtubule–kinetochore attachments and biogenesis of tension-ridden and properly functioning mitotic spindle.

Cerebellar grey matter deficits in first-episode schizophrenia mapped using cortical pattern matching

Cerebellar dysfunction has been proposed to lead to “cognitive dysmetria” in schizophrenia via the cortico-cerebellar-thalamic-cortical circuit, contributing to a range of cognitive and clinical symptoms of the disorder. Here we investigated total cerebellar grey and white matter volumes and cerebellar regional grey matter abnormalities in 13 remitted first-episode schizophrenia patients with less than 2 years’ duration of illness. Patient data were compared to 13 pair-wise age, gender, and handedness-matched healthy volunteers using cortical pattern averaging on high-resolution magnetic resonance images. Total cerebellar volume and total grey matter volumes in first-episode schizophrenia patients did not differ from healthy control subjects, but total cerebellar white matter was increased and total grey to white matter ratios were reduced in patients. Four clusters of cerebellar grey matter reduction were identified: (i) in superior vermis; (ii) in the left lobuli VI; (iii) in right-inferior lobule IX, extending into left lobule IX; and (iv) bilaterally in the areas of lobuli III, peduncle and left flocculus. Grey matter deficits were particularly prominent in right lobuli III and IX, left flocculus and bilateral pedunculi. These cerebellar areas have been implicated in attention control, emotional regulation, social functioning, initiation of smooth pursuit eye movements, eye-blink conditioning, language processing, verbal memory, executive function and the processing of spatial and emotional information. Consistent with common clinical, cognitive, and pathophysiological signs of established illness, our findings demonstrate cerebellar pathology as early as in first-episode schizophrenia.

Reduced motor facilitation during action observation in schizophrenia : a mirror neuron deficit?

Impairments in social cognitive functioning are well documented in schizophrenia, however the neural basis of these deficits is unclear. A recent explanatory model of social cognition centers upon the activity of mirror neurons, which are cortical brain cells that become active during both the performance and observation of behavior. Here, we test for the first time whether mirror neuron functioning is reduced in schizophrenia. Fifteen individuals with schizophrenia or schizoaffective disorder and fifteen healthy controls completed a transcranial magnetic stimulation (TMS) experiment designed to assess mirror neuron activation. While patients demonstrated no abnormalities in cortical excitability, motor facilitation during action observation, putatively reflecting mirror neuron activity, was reduced in schizophrenia. Dysfunction within the mirror neuron system may contribute to the pathophysiology of schizophrenia.

A survey of radiographers' confidence and self-perceived accuracy in frontline image interpretation and their continuing educational preferences

Introduction The provision of a written comment on traumatic abnormalities of the musculoskeletal system detected by radiographers can assist referrers and may improve patient management, but the practice has not been widely adopted outside the United Kingdom. The purpose of this study was to investigate Australian radiographers’ perceptions of their readiness for practice in a radiographer commenting system and their educational preferences in relation to two different delivery formats of image interpretation education, intensive and non-intensive. Methods A cross-sectional web-based questionnaire was implemented between August and September 2012. Participants included radiographers with experience working in emergency settings at four Australian metropolitan hospitals. Conventional descriptive statistics, frequency histograms, and thematic analysis were undertaken. A Wilcoxon signed-rank test examined whether a difference in preference ratings between intensive and non-intensive education delivery was evident. Results The questionnaire was completed by 73 radiographers (68% response rate). Radiographers reported higher confidence and self-perceived accuracy to detect traumatic abnormalities than to describe traumatic abnormalities of the musculoskeletal system. Radiographers frequently reported high desirability ratings for both the intensive and the non-intensive education delivery, no difference in desirability ratings for these two formats was evident (z = 1.66,P = 0.11). Conclusions Some Australian radiographers perceive they are not ready to practise in a frontline radiographer commenting system. Overall, radiographers indicated mixed preferences for image interpretation education delivered via intensive and non-intensive formats. Further research, preferably randomised trials, investigating the effectiveness of intensive and non-intensive education formats of image interpretation education for radiographers is warranted.

Risk factors for delayed healing in venous leg ulcers : a review of the literature

Background Chronic leg ulcers, remaining unhealed after 4–6 weeks, affect 1-3% of the population, with treatment costly and health service resource intensive. Venous disease contributes to approximately 70% of all chronic leg ulcers and these ulcers are often associated with pain, reduced mobility and a decreased quality of life. Despite evidence-based care, 30% of these ulcers are unlikely to heal within a 24-week period and therefore the recognition and identification of risk factors for delayed healing of venous leg ulcers would be beneficial. Aim To review the available evidence on risk factors for delayed healing of venous leg ulcers. Methods: A review of the literature in regard to risk factors for delayed healing in venous leg ulcers was conducted from January 2000 to December 2013. Evidence was sourced through searches of relevant databases and websites for resources addressing risk factors for delayed healing in venous leg ulcers specifically. Results Twenty-seven studies, of mostly low-level evidence (Level III and IV), identified risk factors associated with delayed healing. Risk factors that were consistently identified included: larger ulcer area, longer ulcer duration, a previous history of ulceration, venous abnormalities and lack of high compression. Additional potential predictors with inconsistent or varying evidence to support their influence on delayed healing of venous leg ulcers included decreased mobility and/or ankle range of movement, poor nutrition and increased age. Discussion Findings from this review indicate that a number of physiological risk factors are asso- ciated with delayed healing in venous leg ulcers and that social and/or psychological risk factors should also be considered and examined further. Conclusion The findings from this review can assist health professionals to identify prognostic indicators or risk factors significantly associated with delayed healing in venous leg ulcers. This will facilitate realistic outcome planning and inform implementation of appropriate early strategies to promote healing.

Combination chemotherapy for primary small intestinal lymphoma in the Middle East

Twelve patients with primary small intestinal lymphoma were followed prospectively for 3 years. Endoscopic abnormalities were diagnostic of lymphoma in all cases where the duodenum was involved (83%). In three cases (25%) the disease extended to the stomach. One patient (8%) had diffuse small cell cleaved and 11 (92%) diffuse large cell lymphoma stages I (8%), II (25%), III (58%) and IV (8%). Nine of them were unresectable and primarily treated with combination chemotherapy; 67% achieved complete remission, 22% partial response and 11% no response. Only one patient relapsed and achieved a second remission. All complete remission patients are currently alive and free of disease at a median follow-up of 36 months. Overall survival for all patients is 58%, and disease-free survival is 50%. No instance of chemotherapy-related bleeding or perforation was seen. Tetracycline was necessary for the treatment of IPSID-associated diarrhea and malabsorption in spite of cytotoxic chemotherapy.

Automated ventricular mapping with multi-atlas fluid image alignment reveals genetic effects in Alzheimer's disease

We developed and validated a new method to create automated 3D parametric surface models of the lateral ventricles in brain MRI scans, providing an efficient approach to monitor degenerative disease in clinical studies and drug trials. First, we used a set of parameterized surfaces to represent the ventricles in four subjects' manually labeled brain MRI scans (atlases). We fluidly registered each atlas and mesh model to MRIs from 17 Alzheimer's disease (AD) patients and 13 age- and gender-matched healthy elderly control subjects, and 18 asymptomatic ApoE4-carriers and 18 age- and gender-matched non-carriers. We examined genotyped healthy subjects with the goal of detecting subtle effects of a gene that confers heightened risk for Alzheimer's disease. We averaged the meshes extracted for each 3D MR data set, and combined the automated segmentations with a radial mapping approach to localize ventricular shape differences in patients. Validation experiments comparing automated and expert manual segmentations showed that (1) the Hausdorff labeling error rapidly decreased, and (2) the power to detect disease- and gene-related alterations improved, as the number of atlases, N, was increased from 1 to 9. In surface-based statistical maps, we detected more widespread and intense anatomical deficits as we increased the number of atlases. We formulated a statistical stopping criterion to determine the optimal number of atlases to use. Healthy ApoE4-carriers and those with AD showed local ventricular abnormalities. This high-throughput method for morphometric studies further motivates the combination of genetic and neuroimaging strategies in predicting AD progression and treatment response. © 2007 Elsevier Inc. All rights reserved.

Meta-analysis of structural imaging findings in Attention-Deficit/Hyperactivity Disorder

Background Although there are many structural neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) in children, there are inconsistencies across studies and no consensus regarding which brain regions show the most robust area or volumetric reductions relative to control subjects. Our goal was to statistically analyze structural imaging data via a meta-analysis to help resolve these issues. Methods We searched the MEDLINE and PsycINFO databases through January 2005. Studies must have been written in English, used magnetic resonance imaging, and presented the means and standard deviations of regions assessed. Data were extracted by one of the authors and verified independently by another author. Results Analyses were performed using STATA with metan, metabias, and metainf programs. A meta-analysis including all regions across all studies indicated global reductions for ADHD subjects compared with control subjects, standardized mean difference equal to .408, p less than .001. Regions most frequently assessed and showing the largest differences included cerebellar regions, the splenium of the corpus callosum, total and right cerebral volume, and right caudate. Several frontal regions assessed in only two studies also showed large significant differences. Conclusions This meta-analysis provides a quantitative analysis of neuroanatomical abnormalities in ADHD and information that can be used to guide future studies.

N-ethyl-N-nitrosourea (ENU) induced mutations within the Klotho gene lead to ectopic calcification and reduced lifespan in mouse models

Ectopic calcification (EC), which is the pathological deposition of calcium and phosphate in extra-skeletal tissues, may be associated with hypercalcaemic and hyperphosphataemic disorders, or it may occur in the absence of metabolic abnormalities. In addition, EC may be inherited as part of several monogenic disorders and studies of these have provided valuable insights into the metabolic pathways regulating mineral metabolism. For example, studies of tumoural calcinosis, a disorder characterised by hyperphosphataemia and progressive EC, have revealed mutations of fibroblast growth factor 23 (FGF23), polypeptide N-acetyl galactosaminyltransferase 3 (GALNT3) and klotho (KL), which are all part of a phosphate-regulating pathway. However, such studies in humans are limited by the lack of available large families with EC, and to facilitate such studies we assessed the progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) for EC. This identified two mutants with autosomal recessive forms of EC, and reduced lifespan, designated Ecalc1 and Ecalc2. Genetic mapping localized the Ecalc1 and Ecalc2 loci to a 11.0 Mb region on chromosome 5 that contained the klotho gene (Kl), and DNA sequence analysis identified nonsense (Gln203Stop) and missense (Ile604Asn) Kl mutations in Ecalc1 and Ecalc2 mice, respectively. The Gln203Stop mutation, located in KL1 domain, was severely hypomorphic and led to a 17-fold reduction of renal Kl expression. The Ile604Asn mutation, located in KL2 domain, was predicted to impair klotho protein stability and in vitro expression studies in COS-7 cells revealed endoplasmic reticulum retention of the Ile604Asn mutant. Further phenotype studies undertaken in Ecalc1 (kl203X/203X) mice demonstrated elevations in plasma concentrations of phosphate, FGF23 and 1,25-dihydroxyvitamin D. Thus, two allelic variants of Kl that develop EC and represent mouse models for tumoural calcinosis have been established. © 2015 Esapa et al.

Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, heritable condition typified by progression of extensive ossification within skeletal muscle, ligament and tendon together with defects in skeletal development. The condition is easily diagnosed by the presence of shortened great toes and there is severe advancement of disability with age. FOP has been shown to result from a point mutation (c.617G>A) in the ACVR1 gene in almost all patients reported. Very recently two other mutations have been described in three FOP patients. We present here evidence for two further unique mutations (c.605G>T and c.983G>A) in this gene in two FOP patients with some atypical digit abnormalities and other clinical features. The observation of disparate missense mutations mapped to the GS and kinase domains of the protein supports the disease model of mild kinase activation and provides a potential rationale for phenotypic variation. © 2009 Petrie et al.

Molecular and pathological insights into Chlamydia pecorum-associated sporadic bovine encephalomyelitis (SBE) in Western Australia

Background Despite its global recognition as a ruminant pathogen, cases of Chlamydia pecorum infection in Australian livestock are poorly documented. In this report, a C. pecorum specific Multi Locus Sequence Analysis scheme was used to characterise the C. pecorum strains implicated in two cases of sporadic bovine encephalomyelitis confirmed by necropsy, histopathology and immunohistochemistry. This report provides the first molecular evidence for the presence of mixed infections of C. pecorum strains in Australian cattle. Case presentation Affected animals were two markedly depressed, dehydrated and blind calves, 12 and 16 weeks old. The calves were euthanized and necropsied. In one calf, a severe fibrinous polyserositis was noted with excess joint fluid in all joints whereas in the other, no significant lesions were seen. No gross abnormalities were noted in the brain of either calf. Histopathological lesions seen in both calves included: multifocal, severe, subacute meningoencephalitis with vasculitis, fibrinocellular thrombosis and malacia; diffuse, mild, acute interstitial pneumonia; and diffuse, subacute epicarditis, severe in the calf with gross serositis. Immunohistochemical labelling of chlamydial antigen in brain, spleen and lung from the two affected calves and brain from two archived cases, localised the antigen to the cytoplasm of endothelium, mesothelium and macrophages. C. pecorum specific qPCR, showed dissemination of the pathogen to multiple organs. Phylogenetic comparisons with other C. pecorum bovine strains from Australia, Europe and the USA revealed the presence of two genetically distinct sequence types (ST). The predominant ST detected in the brain, heart, lung and liver of both calves was identical to the C. pecorum ST previously described in cases of SBE. A second ST detected in an ileal tissue sample from one of the calves, clustered with previously typed faecal bovine isolates. Conclusion This report provides the first data to suggest that identical C. pecorum STs may be associated with SBE in geographically separated countries and that these may be distinct from those found in the gastrointestinal tract. This report provides a platform for further investigations into SBE and for understanding the genetic relationships that exist between C. pecorum strains detected in association with other infectious diseases in livestock.