Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency

Objective: To determine the genetic cause of slowly progressive cerebellar ataxia, sensorineural deafness, and hypergonadotropic hypogonadism in 5 patients from 3 different families. Methods: The patients comprised 2 sib pairs and 1 sporadic patient. Clinical assessment included history, physical examination, and brain MRI. Linkage analysis was performed separately on the 2 sets of sib pairs using single nucleotide polymorphism microarrays, followed by analysis of the intersection of the regions. Exome sequencing was performed on 1 affected patient with variant filtering and prioritization undertaken using these intersected regions. Results: Using a combination of sequencing technologies, we identified compound heterozygous mutations in HSD17B4 in all 5 affected patients. In all 3 families, peroxisomal D-bifunctional protein (DBP) deficiency was caused by compound heterozygosity for 1 nonsense/deletion mutation and 1 missense mutation. Conclusions: We describe 5 patients with juvenile DBP deficiency from 3 different families, bringing the total number of reported patients to 14, from 8 families. This report broadens and consolidates the phenotype associated with juvenile DBP deficiency

Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach

Human cancers exhibit strong phenotypic differences that can be visualized noninvasively by medical imaging. Radiomics refers to the comprehensive quantification of tumour phenotypes by applying a large number of quantitative image features. Here we present a radiomic analysis of 440 features quantifying tumour image intensity, shape and texture, which are extracted from computed tomography data of 1,019 patients with lung or head-and-neck cancer. We find that a large number of radiomic features have prognostic power in independent data sets of lung and head-and-neck cancer patients, many of which were not identified as significant before. Radiogenomics analysis reveals that a prognostic radiomic signature, capturing intratumour heterogeneity, is associated with underlying gene-expression patterns. These data suggest that radiomics identifies a general prognostic phenotype existing in both lung and head-and-neck cancer. This may have a clinical impact as imaging is routinely used in clinical practice, providing an unprecedented opportunity to improve decision-support in cancer treatment at low cost

Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5

Whole-exome sequencing of two brothers with drug-resistant, early-onset, focal epilepsy secondary to extensive type IIA focal cortical dysplasia identified a paternally inherited, nonsense variant of DEPDC5 (c.C1663T, p.Arg555*). This variant has previously been reported to cause familial focal epilepsy with variable foci in patients with normal brain imaging. Immunostaining of resected brain tissue from both brothers demonstrated mammalian target of rapamycin (mTOR) activation. This report shows the histopathological features of cortical dysplasia associated with a DEPDC5 mutation, confirms mTOR dysregulation in the malformed tissue and expands the spectrum of neurological manifestations of DEPDC5 mutations to include severe phenotypes with large areas of cortical malformation.Thomas Scerri, Jessica R. Riseley, Greta Gillies, Kate Pope, Rosemary Burgess, Simone A. Mandelstam ... et al

Communication is key: a study of the development of communication key skills in China

Different countries offer alternative curricula around what might be designated language, literacy and/or communication. This paper focuses on the latter which has typically been associated with vocational education and often labelled a ‘key’ or ‘core’ skill that forms part of a wider set of life and employability skills. In recent years, as China has emerged as a global economy, education has been significant in its policy and development. This research explores staff and student responses to the introduction of a key skills communication course in three Chinese further education vocational colleges. The initiative was prompted by research in China which had suggested that communication is important not just for education (Ye and Li 2007) but also for employability, and that the ability to communicate effectively could be instrumental in individuals’ success and development (Tong and Zhong 2008). It explores what communication key skills might mean in a Chinese context and questions notions of transferability and of competence and performance in communication. It analyses how motivation could affect learner success and the relationship of pedagogy to curriculum and, finally, it considers how communication might be an element in the longer-term social and political development of critical literacies

A decision support model for travelling gun irrigation machines

Travelling gun irrigation is a popular form of irrigation in the Queensland dairy, sugar and horticultural industries. High uniformity of irrigation applications is essential to the production of high yields from these crops however, poor uniformity is characteristic of travelling gun machines. For example, Smith et al. (2002) reported that only 25% of machines tested in sugar cane areas near Bundaberg, Qld, gave uniformities greater than the recommended Christiansen Coefficient of Uniformity (CU) of 80%. Simulation of the sprinkler distribution pattern from a travelling gun provides the basis for a powerful and effective decision support model for these machines that will assist extension staff in the development and promotion of optimum irrigation management strategies. Central to the simulation is the prediction of the impact of wind on the sprinkler patterns

Evaluating whole field irrigation performance using statistical inference of inter-furrow infiltration variation

Inter-furrow infiltration variability is often ignored during the evaluation and optimisation of furrow irrigation. Existing techniques for estimating infiltration parameters are generally too intensive in measurement and computation for routine application at the field scale and have therefore primarily been used to study the behaviour of single furrows. This paper identifies the inter-furrow infiltration variation within typical furrow-irrigated fields and determines that this variation can be adequately described using a log-normal distribution. A procedure to predict whole field furrow infiltration characteristics using minimum field measurements is then presented. The technique uses a single advance measurement for single furrows and the log-normal probability distribution to predict the statistical distribution of infiltration functions across the field based on the measured infiltration curve for one or more fully evaluated furrows. This technique also considers the infiltration curve over appropriate ranges of opportunity time. Simulations using the predicted infiltration parameters demonstrate more accurate estimates of the whole field efficiency and uniformity than those extrapolated from infiltration measurements on a limited number of furrows as sampled in a conventional evaluation

The child guidance clinic.

The metabolism of cancer cells differs substantially from normal cells, including ion transport. Although this phenomenon has been long recognized, ion transporters have not been viewed as suitable therapeutic targets. However, the acidic pH values present in tumours which are well outside of normal limits are now becoming recognized as an important therapeutic target. Carbonic anhydrase IX (CAIX) is fundamental to tumour pH regulation. CAIX is commonly expressed in cancer, but lowly expressed in normal tissues and that presents an attractive target. Here, we discuss the possibilities of exploiting the acidic, hypoxic tumour environment as possible target for therapy. Additionally, clinical experience with CAIX targeting in cancer patients is discussed

Textbook of anaesthetics. Sixth edition.

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