Neoplasia in Three Aye-Ayes (Daubentonia madagascariensis)

Tumours diagnosed in three aged captive aye-ayes (Daubentonia madagascariensis), held in two different institutions, are described. A cerebral glioblastoma was diagnosed based on histological and immunohistochemical findings in one of the animals following initial presentation with bilateral mydriasis, absent pupillary reflex, head tilt and ataxia. A second animal was humanely destroyed due to impaired locomotion associated with spondylosis and a post-mortem diagnosis of cholangiocarcinoma was made based on histology with further confirmation with immunohistochemical labelling for cytokeratin 7. A third aye-aye suffering from dental disease was diagnosed with an oral squamous cell carcinoma following an excisional biopsy from a non-healing wound in the lip. Due to progression of the neoplasia the animal was humanely destroyed and post-mortem examination revealed the presence on an additional unilateral phaeochromocytoma

Personality type and work-related outcomes: An exploratory application of the Enneagram model

Despite the Enneagram Personality Typology growing in popularity within the workplace, little research has focused in it. The aims of this study were therefore twofold. First, to establish how the Enneagram Personality Typology relates to personality approaches that are more established within the research literature and second, to explore the relationship between Enneagram types and key workplace attitudes and cognitions. In doing so, the study is the first investigation into the validity and utility of the Enneagram model as a typology approach to personality in the workplace. Four hundred and sixteen participants, the majority in full time employment, completed a questionnaire survey assessing personality (Enneagram type, Big Five traits, personal values, implicit motives) and work-related variables (job attitudes and cognitions and occupational demographics). Enneagram types were distinguished using a unique pattern of traits, values and implicit motives, demonstrating that the typology provides a way of describing the “whole person”. In addition, each of the types had different relationships with the work variables, with the Enneagram model having predictive utility on a par with the personal values and implicit motives, and in one case higher predictive utility than the Big Five. With its focus on self-development and the identification of hidden potential, the Enneagram typology might provide a powerful tool for employee development and talent management. The integrative rather than reductionist approach to personality encourages a more realistic understanding of individual behaviour at work

A rare case of bone marrow infiltration by medulloblastoma in a child.

A seven-year-old boy was previously treated for the primarya posterior fossa tumour, medulloblastoma, with extensive central nervous system metastases including leptomeningeal and intrathecal spinal disease; methylation profiling confirmed a Group 4 tumour. At initial presentation a chemotherapy approach was preferred, due to both his young age and extent of disease; this achieved complete radiological and cytological remission prior to consolidation with high-dose chemotherapy and autologous stem cell rescue. He then experienced an asymptomatic localised posterior fossa relapse on surveillance imaging, treated with complete surgical resection, craniospinal irradiation and maintenance chemotherapy. This chemotherapy was interrupted due to poor count recovery following irradiation, and a bone marrow aspirate and trephine were performed which excluded metastatic medulloblastoma or secondary leukaemia. Alternative maintenance with temozolomide was well tolerated. Unfortunately, end-of-treatment MRI imaging of the neuro-axis revealed an asymptomatic new small enhancing intracranial lesion. An early repeat MRI was performed six weeks later which showed minor progression of the intracranial disease and no intrathecal metastases, but new low T1 signal in multiple vertebral bodies with sparing of T3 and T7 vertebrae (arrows; left image) compared with the imaging performed just six weeks previously. Full blood count revealed Hb 97 g/l, WCC 7.7 x109/l, neutrophils 5.4 x109/l and platelets 204 x109/l. In view of the radiological appearances, bone marrow aspirate and trephine were performed from the posterior iliac crest. Aspirate revealed heavy infiltration with clusters of non-haematopoietic cells, characterized by high nuclear:cytoplasmic ratio, open chromatin and agranular, pale basophilic cytoplasm with vacuolation (right upper image). Trephine immunohistochemistry demonstrated positive staining for synaptophysin, CD56, Neu-N (right lower image), retained INI1 and negative CD99 and desmin, confirming medulloblastoma. Spread of medulloblastoma to the bone marrow is a very rare event. In this case, despite an unremarkable full blood count, radiological changes in the spinal column correlated with easily identified disease in aspirate and trephine samples taken from the posterior iliac crest suggesting widespread marrow infiltration were confirmed by bone marrow examination. Early identification of extracranial metastasis afforded the family and clinicians the opportunity to make informed choices regarding ongoing management

Proton radiography and tomography with application to proton therapy

Proton radiography and tomography have long promised benefit for proton therapy. Their first suggestion was in the early 1960s and the first published proton radiographs and CT images appeared in the late 1960s and 1970s, respectively. More than just providing anatomical images, proton transmission imaging provides the potential for the more accurate estimation of stopping-power ratio (SPR) inside a patient and hence improved treatment planning and verification. With the recent explosion in growth of clinical proton therapy facilities, the time is perhaps ripe for the imaging modality to come to the fore. Yet many technical challenges remain to be solved before proton CT scanners become commonplace in the clinic. Research and development in this field is currently more active that at any time with several prototype designs emerging. This review introduces the principles of proton radiography and tomography, its historical developments, the raft of modern prototype systems and the primary design issues

Performance of a novel wafer scale CMOS active pixel sensor for bio-medical imaging

Recently CMOS Active Pixels Sensors (APSs) have become a valuable alternative to amorphous Silicon and Selenium Flat Panel Imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ≤ 1.9%. The uniformity of the image quality performance has been further investigated in a typical X-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practise. Finally, in order to compare the detection capability of this novel APS with the currently used technology (i.e. FPIs), theoretical evaluation of the Detection Quantum Efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this detector compared to FPIs. Optical characterization, X-ray contrast measurements and theoretical DQE evaluation suggest that a trade off can be found between the need of a large imaging area and the requirement of a uniform imaging performance, making the DynAMITe large area CMOS APS suitable for a range of bio-medical applications

Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology

Despite the early recognition of the potential of proton imaging to assist proton therapy (Cormack 1963 J. Appl. Phys. 34 2722), the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as computed tomography (CT), the water-equivalent-path-length that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS active pixel sensor technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed

A critical control point approach to the removal of chemicals of concern from water for reuse

The reuse of water in a range of potable and non-potable applications is an important factor in the augmentation of water supply and in improving water security and productivity worldwide. A key hindrance to the reuse of water is the cost of compliance testing and process validation associated with ensuring that pathogen and chemicals in the feedwater are removed to a level that ensures no acute or chronic health and/or environmental effects. The critical control point (CCP) approach is well established and widely adopted by water utilities to provide an operational and risk management framework for the removal of pathogens in the treatment system. The application of a CCP approach to barriers in a treatment system for the removal of chemicals is presented. The application exemplar is to a small community wastewater treatment system that aims to produce potable quality water from a secondary treated wastewater effluent, however, the concepts presented are generic. The example used seven treatment barriers, five of which were designed and operated as CCP barriers for pathogens. The work demonstrates a method and risk management framework by which three of the seven barriers could also include a CCP approach for the removal of chemicals. Analogous to a CCP approach for pathogens, the potential is to reduce the use of chemical analysis as a routine determinant of performance criteria. The operational deployment of a CCP approach for chemicals was augmented with the development of a decision tree encompassing the classification of chemicals and the total removal credits across the treatment train in terms of the mechanistic removal of chemicals for each barrier. Validation of the approach is shown for an activated sludge, ozone and reverse osmosis barrier

Geant4-based simulations of charge collection in CMOS Active Pixel Sensors

Geant4 is an object-oriented toolkit for the simulation of the interaction of particles and radiation with matter. It provides a snapshot of the state of a simulated particle in time, as it travels through a specified geometry. One important area of application is the modelling of radiation detector systems. Here, we extend the abilities of such modelling to include charge transport and sharing in pixelated CMOS Active Pixel Sensors (APSs); though similar effects occur in other pixel detectors. The CMOS APSs discussed were developed in the framework of the PRaVDA consortium to assist the design of custom sensors to be used in an energy-range detector for proton Computed Tomography (pCT). The development of ad-hoc classes, providing a charge transport model for a CMOS APS and its integration into the standard Geant4 toolkit, is described. The proposed charge transport model includes, charge generation, diffusion, collection, and sharing across adjacent pixels, as well as the full electronic chain for a CMOS APS. The proposed model is validated against experimental data acquired with protons in an energy range relevant for pCT

Improving continence in children and young people with neurodisability: a systematic review and survey.

Children and young people with neurodisability often need help to achieve socially acceptable bladder and bowel control. Approaches vary depending on whether or not the impairment results from spinal cord pathology that impairs motor control and sensation of the bladder and bowel. Currently, there is uncertainty about which interventions are effective. The objective was to summarise the available evidence on and current practice for improving continence in children and young people with neurodisability. A systematic review of the effectiveness, cost-effectiveness and factors that modify intervention implementation, alongside a cross-sectional, online survey of current practice with health professionals, parent carers, school and care staff and young people with neurodisability. Twelve databases were searched in the review, resulting in 5756 references; 71 studies (72 papers) were included in the analyses. Most of the evidence was for children with spinal cord pathology, which involved evaluations of pharmacological approaches and surgical techniques, whereas the evidence pertaining to those with non-spinal-cord-related pathology tended to be for behavioural interventions. The methodological quality of studies was rated as being moderate to poor. There were three robust qualitative studies about the experience of continence among children with spinal cord pathology. We found substantial heterogeneity across the interventions that we evaluated in terms of quality, study design and outcomes measured. No economic studies were found. The results were synthesised narratively and reported in text and tables. We did not find any eligible studies evaluating interventions using toilet and clothing adaptations in the review, although the survey highlighted that these types of interventions are frequently used and considered. In total, 949 people responded to the survey: 202 health professionals, 605 parent carers, 122 school and social care staff, and 20 young people. The survey results illustrated the different roles that professionals have in improving continence, highlighting the importance of a multidisciplinary approach to supporting children and young people and their families. Clinicians employ a range of assessments and interventions to improve continence or independent toileting, depending on the needs of the child. Quantitative studies in the review were not methodologically robust. The survey had a risk of response bias. Our research found a dearth of good-quality evidence for many of the interventions currently in use, and no evidence of experiences of implementing interventions for children with non-spinal-cord-related pathology. There was also no evidence of cost-effectiveness of any of the interventions. There is a need to involve young people and families in the design of high-quality evaluative research for interventions that aim to improve continence. This is especially the case for children with autism and learning disability, who have been neglected in previous evaluative and qualitative research. We recommend better training for health, education and care professionals about toileting, informed by evidence and the lived experiences of children and their families. We recommend a joined-up multidisciplinary and holistic approach to improving continence to maximise independence, dignity and comfort. It is vital that children and young people with neurodisability have early access to regular, integrated assessment of their bladder and bowel health, and are fully supported with appropriate personalised treatment. This study is registered as PROSPERO CRD42018100572. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 73. See the NIHR Journals Library website for further project information