GCS programmer's manual

A variety of instructions to be used in the development of implementations of software for the Guidance and Control Software (GCS) project is described. This document fulfills the Radio Technical Commission for Aeronautics RTCA/DO-178A guidelines, 'Software Considerations in Airborne Systems and Equipment Certification' requirements for document No. 4, which specifies the information necessary for understanding and programming the host computer, and document No. 12, which specifies the software design and implementation standards that are applicable to the software development and testing process. Information on the following subjects is contained: activity recording, communication protocol, coding standards, change management, error handling, design standards, problem reporting, module testing logs, documentation formats, accuracy requirements, and programmer responsibilities

Bacterial Cell Enlargement Requires Control of Cell Wall Stiffness Mediated by Peptidoglycan Hydrolases.

Most bacterial cells are enclosed in a single macromolecule of the cell wall polymer, peptidoglycan, which is required for shape determination and maintenance of viability, while peptidoglycan biosynthesis is an important antibiotic target. It is hypothesized that cellular enlargement requires regional expansion of the cell wall through coordinated insertion and hydrolysis of peptidoglycan. Here, a group of (apparent glucosaminidase) peptidoglycan hydrolases are identified that are together required for cell enlargement and correct cellular morphology of Staphylococcus aureus, demonstrating the overall importance of this enzyme activity. These are Atl, SagA, ScaH, and SagB. The major advance here is the explanation of the observed morphological defects in terms of the mechanical and biochemical properties of peptidoglycan. It was shown that cells lacking groups of these hydrolases have increased surface stiffness and, in the absence of SagB, substantially increased glycan chain length. This indicates that, beyond their established roles (for example in cell separation), some hydrolases enable cellular enlargement by making peptidoglycan easier to stretch, providing the first direct evidence demonstrating that cellular enlargement occurs via modulation of the mechanical properties of peptidoglycan. IMPORTANCE: Understanding bacterial growth and division is a fundamental problem, and knowledge in this area underlies the treatment of many infectious diseases. Almost all bacteria are surrounded by a macromolecule of peptidoglycan that encloses the cell and maintains shape, and bacterial cells must increase the size of this molecule in order to enlarge themselves. This requires not only the insertion of new peptidoglycan monomers, a process targeted by antibiotics, including penicillin, but also breakage of existing bonds, a potentially hazardous activity for the cell. Using Staphylococcus aureus, we have identified a set of enzymes that are critical for cellular enlargement. We show that these enzymes are required for normal growth and define the mechanism through which cellular enlargement is accomplished, i.e., by breaking bonds in the peptidoglycan, which reduces the stiffness of the cell wall, enabling it to stretch and expand, a process that is likely to be fundamental to many bacteria

Pituitary xanthogranulomas: clinical features, radiological appearances and post-operative outcomes

Background Xanthogranulomas are inflammatory masses most commonly found at peripheral sites such as the skin. Sellar and parasellar xanthogranulomas are rare and present a diagnostic challenge as they are difficult to differentiate from other sellar lesions such as craniopharyngiomas and Rathke’s cleft cysts pre-operatively. Their radiological imaging features are yet to be clearly defined, and clinical outcomes after surgery are also uncertain. This study reviews clinical presentation, radiological appearances, and clinical outcomes in a cohort of patients with pituitary xanthogranulomas. Methods A prospectively maintained pituitary surgery database was screened for histologically confirmed pituitary xanthogranulomas between May 2011–December 2016. Retrospective case note assessments were then performed by three independent reviewers. Patient demographics, clinical presentations, imaging, and clinical outcomes were analysed. Results During the study period 295 endoscopic endonasal pituitary surgeries were performed. Six patients had confirmed pituitary xanthogranulomas (2%). Patients most commonly presented with visual field deficits and/or endocrine dysfunction. Common imaging features included: a cystic consistency, hyperintensity on T1-weighted MR images, and contrast enhancement either peripherally (n = 3) or homogenously (n = 3). The most common pre-operative endocrine deficits were hyperprolactinaemia and hypoadrenalism (at least one of which was identified in 4/6 patients; 66%). Thirty-three percent (2/6) of patients presented with diabetes insipidus. The most common post-operative endocrinological deficits were adrenocortical dysfunction (66%) and gonadotropin deficiency (66%). Visual assessments normalised in all six patients post-operatively. Gross total resection was achieved in all patients, and at median follow up of 33.5 months there were no cases of tumour recurrence. Conclusions The prevalence of pituitary xanthogranulomas in our series is higher than that suggested in the literature. Surgery restored normal vision to all cases, however four patients (67%) required long-term hormonal replacement post-operatively. Imaging features such peripheral rim enhancement, a suprasellar tumour epicentre, and the absence of both calcification or cavernous sinus invasion were identified as potential indicators that together should alert clinicians to the possibility of pituitary xanthogranuloma when assessing patients with cystic sellar and parasellar tumours

Cerebral salt wasting following traumatic brain injury

Hyponatraemia is the most commonly encountered electrolyte disturbance in neurological high dependency and intensive care units. Cerebral salt wasting (CSW) is the most elusive and challenging of the causes of hyponatraemia, and it is vital to distinguish it from the more familiar syndrome of inappropriate antidiuretic hormone (SIADH). Managing CSW requires correction of the intravascular volume depletion and hyponatraemia, as well as mitigation of on-going substantial sodium losses. Herein we describe a challenging case of CSW requiring large doses of hypertonic saline and the subsequent substantial benefit with the addition of fludrocortisone

Removing Orbital Debris with Lasers

Orbital debris in low Earth orbit (LEO) are now sufficiently dense that the use of LEO space is threatened by runaway collisional cascading. A problem predicted more than thirty years ago, the threat from debris larger than about 1 cm demands serious attention. A promising proposed solution uses a high power pulsed laser system on the Earth to make plasma jets on the objects, slowing them slightly, and causing them to re-enter and burn up in the atmosphere. In this paper, we reassess this approach in light of recent advances in low-cost, light-weight modular design for large mirrors, calculations of laser-induced orbit changes and in design of repetitive, multi-kilojoule lasers, that build on inertial fusion research. These advances now suggest that laser orbital debris removal (LODR) is the most cost-effective way to mitigate the debris problem. No other solutions have been proposed that address the whole problem of large and small debris. A LODR system will have multiple uses beyond debris removal. International cooperation will be essential for building and operating such a system.Comment: 37 pages, 15 figures, in preparation for submission to Advances in Space Researc

Evolution of design considerations in complex craniofacial reconstruction using patient-specific implants

Previously published evidence has established major clinical benefits from using Computer Aided Design (CAD), Computer Aided Manufacturing (CAM), and Additive Manufacturing (AM) to produce patient-specific devices. These include cutting guides, drilling guides, positioning guides, and implants. However, custom devices produced using these methods are still not in routine use – particularly by the UK National Health Service (NHS). Oft-cited reasons for this slow uptake include: a higher up-front cost than conventionally-fabricated devices, material-choice uncertainty, and a lack of long-term follow-up due to their relatively recent introduction. This paper identifies a further gap in current knowledge – that of design rules, or key specification considerations for complex CAD/CAM/AM devices. This research begins to address the gap by combining a detailed review of the literature with first-hand experience of interdisciplinary collaboration on five craniofacial patient case-studies. In each patient case, bony lesions in the orbito-temporal region were segmented, excised, and reconstructed in the virtual environment. Three cases translated these digital plans into theatre via polymer surgical guides. Four cases utilised AM to fabricate titanium implants. One implant was machined from PolyEther Ether Ketone (PEEK). From the literature, articles with relevant abstracts were analysed to extract design considerations. 19 frequently-recurring design considerations were extracted from previous publications. 9 new design considerations were extracted from the case studies – on the basis of subjective clinical evaluation. These were synthesised to produce a design considerations framework to assist clinicians with prescribing and design engineers with modelling. Promising avenues for further research are proposed