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Dive into the research topics where Alistair Calder is active.

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Featured researches published by Alistair Calder.


Thorax | 2011

Lung Clearance Index and HRCT are complementary markers of lung abnormalities in young children with CF

Catherine M. Owens; Paul Aurora; Sanja Stanojevic; Andrew Bush; Angie Wade; C Oliver; Alistair Calder; John Price; Siobhán B. Carr; Anu Shankar; Janet Stocks

Rationale High resolution computed tomography (HRCT) is a more sensitive tool for detecting early cystic fibrosis (CF) lung disease than either spirometry or plain radiography, but its relationship to other measures of lung function has not been established in young children. Objectives 1) To assess whether the lung clearance index (LCI) derived from multiple breath inert-gas washout (MBW) is as effective as HRCT in identifying pulmonary abnormalities; and 2) explore the relationships between abnormalities detected by HRCT and by spirometry, plethysmography and MBW (collectively, LFTs) in young children with CF. Methods Children with CF underwent LFTs and volumetric HRCT on the same day. Healthy age-matched controls underwent identical LFTs without HRCT. Scans were anonymised, and scored using the Brody-II CT scoring system, to assess for presence and extent of bronchiectasis, airway wall thickening, mucus plugging, and parenchymal opacities. Results Assessments were undertaken in 60 children with CF (mean (SD) 7.8 (1.3) years) and 54 healthy controls (7.9 (1.2) y). Among children with CF, 84% (47/56) had abnormal LCI, 58% (27/47) abnormal plethysmographic lung volumes (FRCpleth or RV), 35% (21/60) abnormal sRaw and 47% (28/60) abnormal spirometry (FEV1 or FEF25–75); whereas HRCT scans were abnormal in 85% (51/60): median total Brody-II score: 9.5% (range 0–51%). Total CT score correlated more strongly with LCI (Spearman correlation=0.77) than with spirometry (R=−0.43) or any other marker of lung function. Of the nine children with normal LCI, five had abnormalities on HRCT, whereas five children with normal HRCT had raised LCI. Conclusions These results suggest that while LCI and HRCT have similar sensitivity to detect CF lung disease, complimentary information may be gained in individual patients.


Pediatric Radiology | 2009

Imaging of parapneumonic pleural effusions and empyema in children

Alistair Calder; Catherine M. Owens

Pleural empyema in children is increasing in incidence. The British Thoracic Society published guidelines for the management of empyema in children in 2005, including recommendations regarding imaging. In this article we review the pathophysiology, treatment options and imaging findings of complicated parapneumonic effusion and empyema in children. We also review the published evidence that supports the roles imaging is called upon to play in the management of these conditions. Imaging in the form of chest radiography and US is recommended to identify and guide drainage of complicated parapneumonic effusions. CT is recommended in special circumstances only. Imaging techniques have not been shown to accurately stage empyema, predict outcome or guide decisions regarding surgical versus medical management.


Thorax | 2008

Role of routine computed tomography in paediatric pleural empyema

Adam Jaffe; Alistair Calder; Catherine M. Owens; Sanja Stanojevic; Samatha Sonnappa

Background: The incidence of empyema in children is increasing worldwide. While there are emerging data for the best treatment options, there is little evidence to support the imaging modalities used to guide treatment, particularly with regard to the role of routine CT scanning. The aims of this study were to develop a radiological scoring system for paediatric empyema and to assess the utility of routine CT scanning in this disease. Methods: Children with empyema were prospectively enrolled over a 3-year period into a randomised clinical trial of video-assisted thoracoscopic surgery versus percutaneous chest drain insertion and urokinase. All children received a preoperative chest radiograph (CXR), pleural ultrasound scan (USS) and chest CT scan. In the urokinase arm the clinician inserted the drain with USS evidence only and did not have access to the CT scan at the time of insertion to reflect clinical practice. A scoring system was developed for each individual radiological modality and used to compare imaging characteristics of the pleural fluid collection and underlying parenchyma and to assess the utility of USS and CT to predict length of stay after the intervention. Results: Of the 60 subjects recruited, 46 had USS images available for review, 36 had a CT scan which met the inclusion criteria and 31 had all three radiological measurements (CT, USS and CXR) available for analysis. There was substantial interobserver agreement for USS grades (κ = 0.709) and moderate agreement for total CT scores (κ = 0.520). There were weak correlations between USS grade and total CT score as well as CT loculation and density scores. Of the 25 CXRs showing simple opacification of the underlying parenchyma only, CT demonstrated simple consolidation (n = 14), necrotising pneumonia (n = 7), cavitary necrosis (n = 3) and pneumatoceles (n = 1). No abnormality was detected on CT scanning which directly altered clinical management. Neither the USS score nor the CT score, nor a combination of the two, were able to predict length of hospital stay. Conclusions: CT scanning detects more parenchymal abnormalities than chest radiography. However, the additional information does not alter management and is unable to predict clinical outcome. This suggests that there is no role for the routine use of CT scanning in children if treated with urokinase and percutaneous chest drain. The omission of routine CT scanning in empyema will reduce the exposure of children to unnecessary radiation and reduce costs. Trial registration number: The trial is fully registered with clinicaltrials.gov (ID: NCT00144950).


Pediatric Pulmonology | 2009

Bronchiectasis secondary to primary immunodeficiency in children: longitudinal changes in structure and function

Katerina Haidopoulou; Alistair Calder; Alison Jones; Adam Jaffe; Samatha Sonnappa

Primary immunodeficiency is a common cause of bronchiectasis in children. The term bronchiectasis suggests an irreversible process; however, disease progression following treatment is controversial. The aim of this study was to evaluate the progression of bronchiectasis in children with primary immunodeficiency after institution of treatment.


Thorax | 2014

Is chest CT useful in newborn screened infants with cystic fibrosis at 1 year of age

Lena P Thia; Alistair Calder; Janet Stocks; Andrew Bush; Catherine M. Owens; Colin Wallis; Carolyn Young; Yvonne Sullivan; Angie Wade; Angus McEwan; Alan S. Brody

Rationale Sensitive outcome measures applicable in different centres to quantify and track early pulmonary abnormalities in infants with cystic fibrosis (CF) are needed both for clinical care and interventional trials. Chest CT has been advocated as such a measure yet there is no validated scoring system in infants. Objectives The objectives of this study were to standardise CT data collection across multiple sites; ascertain the incidence of bronchial dilatation and air trapping in newborn screened (NBS) infants with CF at 1 year; and assess the reproducibility of Brody-II, the most widely used scoring system in children with CF, during infancy. Methods A multicentre observational study of early pulmonary lung disease in NBS infants with CF at age 1 year using volume-controlled chest CT performed under general anaesthetic. Main results 65 infants with NBS-diagnosed CF had chest CT in three centres. Small insignificant variations in lung recruitment manoeuvres but significant centre differences in radiation exposures were found. Despite experienced scorers and prior training, with the exception of air trapping, inter- and intraobserver agreement on Brody-II score was poor to fair (eg, interobserver total score mean (95% CI) κ coefficient: 0.34 (0.20 to 0.49)). Only 7 (11%) infants had a total CT score ≥12 (ie, ≥5% maximum possible) by either scorer. Conclusions In NBS infants with CF, CT changes were very mild at 1 year, and assessment of air trapping was the only reproducible outcome. CT is thus of questionable value in infants of this age, unless an improved scoring system for use in mild CF disease can be developed.


Nature Genetics | 2014

Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome

Sérgio B. Sousa; Dagan Jenkins; Estelle Chanudet; Guergana Tasseva; Miho Ishida; Glenn Anderson; James Docker; Mina Ryten; Joaquim de Sá; Jorge M. Saraiva; Angela Barnicoat; Richard W. Scott; Alistair Calder; Duangrurdee Wattanasirichaigoon; Krystyna H. Chrzanowska; Martina Simandlova; Lionel Van Maldergem; Philip Stanier; Philip L. Beales; Jean E. Vance; Gudrun E. Moore

Lenz-Majewski syndrome (LMS) is a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. By using whole-exome sequencing and selecting variants consistent with the predicted dominant de novo etiology of LMS, we identified causative heterozygous missense mutations in PTDSS1, which encodes phosphatidylserine synthase 1 (PSS1). PSS1 is one of two enzymes involved in the production of phosphatidylserine. Phosphatidylserine synthesis was increased in intact fibroblasts from affected individuals, and end-product inhibition of PSS1 by phosphatidylserine was markedly reduced. Therefore, these mutations cause a gain-of-function effect associated with regulatory dysfunction of PSS1. We have identified LMS as the first human disease, to our knowledge, caused by disrupted phosphatidylserine metabolism. Our results point to an unexplored link between phosphatidylserine synthesis and bone metabolism.


Pediatric Radiology | 2014

Routine perinatal and paediatric post-mortem radiography: detection rates and implications for practice

Owen J. Arthurs; Alistair Calder; Liina Kiho; Andrew M. Taylor; Nj Sebire

BackgroundRoutine perinatal and paediatric post-mortem plain radiography allows for the diagnosis and assessment of skeletal dysplasias, fractures and other bony abnormalities.ObjectiveThe aim of this study was to review the diagnostic yield of this practice.Materials and methodsWe identified 1,027 cases performed in a single institution over a 2½-year period, including babygrams (whole-body examinations) and full skeletal surveys. Images were reported prior to autopsy in all cases. Radiology findings were cross-referenced with the autopsy findings using an autopsy database. We scored each case from 0 to 4 according to the level of diagnostic usefulness.ResultsThe overall abnormality rate was 126/1,027 (12.3%). There was a significantly higher rate of abnormality when a skeletal survey was performed (18%) rather than a babygram (10%; P < 0.01); 90% (665/739) of babygrams were normal. Of the 74 abnormal babygrams, we found 33 incidental non-contributory cases, 19 contributory, 20 diagnostic, and 2 false-positive cases. There were only 2 cases out of 739 (0.27%) in whom routine post-mortem imaging identified potentially significant abnormalities that would not have been detected if only selected imaging had been performed. A policy of performing selected, rather than routine, foetal post-mortem radiography could result in a significant cost saving.ConclusionRoutine post-mortem paediatric radiography in foetuses and neonates is neither diagnostically useful nor cost-effective. A more evidence-based, selective protocol should yield significant cost savings.


Pediatric Radiology | 2014

Scoring of chest CT in children with cystic fibrosis: state of the art

Alistair Calder; Andrew Bush; Alan S. Brody; Catherine M. Owens

Chest CT has been proposed as a surrogate outcome measure in the evaluation of cystic fibrosis lung disease. Quantitative evaluation of chest CT findings requires application of a scoring system to derive numerical values. Several scoring systems are in use. These mostly rely on a subjective judgement of the severity and extent of various features of cystic fibrosis lung disease, including bronchiectasis, bronchial wall thickening, mucous plugging and air-trapping. Scores can subsequently be added to produce a total score. The precision or reproducibility of scoring systems has been assessed but with heterogeneous statistical approaches. Total scores appear to have high levels of reproducibility, but this might mask poorer levels of agreement for individual observations and component scores. It can also be questioned whether total scores are biologically meaningful, as compared to assessments of individual features. Various studies suggest that CT scores give an accurate indicator of the severity of disease, and CT scores might be the best predictors of long-term outcome, but data in this area are limited. CT scores are more sensitive than traditional lung-function indices such as FEV; however the lung clearance index, by multiple breath washout, appears to offer comparable sensitivity to CT. It is not clear whether CT scores are adequately responsive to changes in disease severity in the short to medium term; this is a challenge to the use of CT as a surrogate outcome measure for clinical trials of therapies specific to cystic fibrosis. Cystic fibrosis scoring would benefit from greater levels of standardisation in terms of CT techniques, scoring system, training of observers and measures of reproducibility. Automated approaches to quantifying CT parameters might also offer improved precision. The benefits of chest CT must be weighed against the principal drawback of radiation exposure. The case for more widespread use of chest CT would be strengthened if precision of CT scoring were improved.


American Journal of Human Genetics | 2013

SAMS, a Syndrome of Short Stature, Auditory-Canal Atresia, Mandibular Hypoplasia, and Skeletal Abnormalities Is a Unique Neurocristopathy Caused by Mutations in Goosecoid

David A. Parry; Clare V. Logan; Alexander P.A. Stegmann; Zakia Abdelhamed; Alistair Calder; Shabana Khan; David T. Bonthron; Virginia Clowes; Eamonn Sheridan; Neeti Ghali; Albert E. Chudley; Angus Dobbie; Constance Stumpel; Colin A. Johnson

Short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities (SAMS) has been reported previously to be a rare, autosomal-recessive developmental disorder with other, unique rhizomelic skeletal anomalies. These include bilateral humeral hypoplasia, humeroscapular synostosis, pelvic abnormalities, and proximal defects of the femora. To identify the genetic basis of SAMS, we used molecular karyotyping and whole-exome sequencing (WES) to study small, unrelated families. Filtering of variants from the WES data included segregation analysis followed by comparison of in-house exomes. We identified a homozygous 306 kb microdeletion and homozygous predicted null mutations of GSC, encoding Goosecoid homeobox protein, a paired-like homeodomain transcription factor. This confirms that SAMS is a human malformation syndrome resulting from GSC mutations. Previously, Goosecoid has been shown to be a determinant at the Xenopus gastrula organizer region and a segment-polarity determinant in Drosophila. In the present report, we present data on Goosecoid protein localization in staged mouse embryos. These data and the SAMS clinical phenotype both suggest that Goosecoid is a downstream effector of the regulatory networks that define neural-crest cell-fate specification and subsequent mesoderm cell lineages in mammals, particularly during shoulder and hip formation. Our findings confirm that Goosecoid has an essential role in human craniofacial and joint development and suggest that Goosecoid is an essential regulator of mesodermal patterning in mammals and that it has specific functions in neural crest cell derivatives.


Pediatric Radiology | 2009

Embryonal rhabdomyosarcoma of the omentum: two cases occurring in children

Rebecca S. Leung; Alistair Calder; Derek J. Roebuck

Rhabdomyosarcoma is a soft-tissue malignancy that represents approximately 4–8% of all solid tumours in children and commonly arises from the head and neck and genitourinary system. Intraperitoneal rhabdomyosarcoma, in particular with omental involvement, has been rarely reported in the literature. Furthermore, reports of omental rhabdomyosarcoma of embryonal origin do not exist, to our knowledge. We report two cases of omental embryonal rhabdomyosarcoma affecting children and illustrate the imaging characteristics of this rare tumour.

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Owen J. Arthurs

Great Ormond Street Hospital

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Catherine M. Owens

Great Ormond Street Hospital

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Nj Sebire

Great Ormond Street Hospital

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Richard H. Scott

Great Ormond Street Hospital

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Susan C. Shelmerdine

Great Ormond Street Hospital for Children NHS Foundation Trust

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Derek J. Roebuck

Great Ormond Street Hospital

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Emma Wakeling

London North West Healthcare NHS Trust

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Nagarajan Muthialu

Great Ormond Street Hospital

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Andrew Bush

National Institutes of Health

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