The importance of strategic financial leadership in the UK public sector in a time of financial austerity

Given the severity of financial pressures on public authorities, this report is concerned with how finance managers in public services are coping with the demands placed on them and how they can demonstrate improved value by providing more effective strategic financial leadership. It considers how they are applying managerial approaches and solutions to the challenges of austerity and the role that the public sector finance function can play in this process

Variation conscious assembly fixturing methodologies for the preliminary weld processes of segmented ring structures

This project was sponsored by Rolls-Royce, who had an interest in using scientific principles to improve the geometric accuracy (circularity) of large welded annular structures. This project therefore critically examines and models the mechanisms by which manufacturing variation in wedges components stack and propagate to influence the final assembly geometry. The Trent 900 (T900) Front Bearing Housing (FBH) Ring of Vanes (RoV), was used as an illustrative test-piece, so that the typical sources of variation in large annular assemblies could identified. Also examined was the interplay between assembly gaps created by component variation played and the thermal-mechanical distortions of the Preliminary Welding Process (PWP). Based on the fundamental sight gained form the illustrative test-piece a number of novel Variation Conscious Assembly Fixturing (VCAF) methodologies are proposed. The VCAF methodologies: the Circumscribed Geometric (CG), Inscribed Geometric (IG) and Translation Build (TB) are based on mathematical models of the wedge component and their assembly. The VCAF approaches generate in-fixture build conditions that are idealised for circularity by correcting the positions of the assembly locators in response to component variations. To experimentally validate the proposed VCAF fixturing methodologies, a ring assembly comprising of ten wedge-shaped components was designed and manufactured. In addition to the ten nominal assembly components (containing only implicit manufacturing variation), a number of explicitly oversized and undersized assembly components were also produced. Furthermore, a flexible test-bench fixture was also designed and built, its flexibility allowed it to utilise any of the proposed VCAF build methods, while also accommodating traditional fixed location diameter builds. This allowed each of the proposed and established fixturing methodologies to be tested in the same fixture, keeping fixturing errors consistent. Additionally, as the assembly input variation of the components could be controlled; so by purposely inducing an error into the assembly, and measuring the resultant circularity, the response of each build method to the input variation could be assessed. Working in this way the new CG method was shown to be the most effective at controlling circularity of annular assemblies, showing a 5x circularity improvement over the traditional fixed build diameter location approaches. The relationship between manufacturing variation and thermo-mechanical weld distortion is also presented in this research. Using a series of fixtured and free-state plate assemblies, the influence of inter-component gaps on PWP distortion has been experimentally studied and evaluated. The knowledge generated during these tests was then used to augment a Finite Element (FE) simulation of the welding process. Once the nature of the gap/weld interdependence was identified, a series of ring structures were welded. These ring assemblies demonstrated that with an understanding of the gap/weld interdependence PWP distortion could be substantially reduced

The kainate receptor antagonist UBP310 but not single deletion of GluK1, GluK2, or GluK3 subunits, inhibits MPTP-induced degeneration in the mouse midbrain

© 2019 Elsevier Inc. The excitatory neurotransmitter glutamate is essential in basal ganglia motor circuits and has long been thought to contribute to cell death and degeneration in Parkinson's disease (PD). While previous research has shown a significant role of NMDA and AMPA receptors in both excitotoxicity and PD, the third class of ionotropic glutamate receptors, kainate receptors, have been less well studied. Given the expression of kainate receptor subunits GluK1-GluK3 in key PD-related brain regions, it has been suggested that GluK1-GluK3 may contribute to excitotoxic cell loss. Therefore the neuroprotective potential of the kainate receptor antagonist UBP310 in animal models of PD was investigated in this study. Stereological quantification revealed administration of UBP310 significantly increased survival of dopaminergic and total neuron populations in the substantia nigra pars compacta in the acute MPTP mouse model of PD. In contrast, UBP310 was unable to rescue MPTP-induced loss of dopamine levels or dopamine transporter expression in the striatum. Furthermore, deletion of GluK1, GluK2 or GluK3 had no effect on MPTP or UBP310-mediated effects across all measures. Interestingly, UBP310 did not attenuate cell loss in the midbrain induced by intrastriatal 6-OHDA toxicity. These results indicate UBP310 provides neuroprotection in the midbrain against MPTP neurotoxicity that is not dependent on specific kainate receptor subunits

The relationship between mandibular advancement, tongue movement, and treatment outcome in obstructive sleep apnea

Study Objectives: To characterize how mandibular advancement enlarges the upper airway via posterior tongue advancement in people with obstructive sleep apnea (OSA) and whether this is associated with mandibular advancement splint (MAS) treatment outcome. Methods: One-hundred and one untreated people with OSA underwent a 3T magnetic resonance (MRI) scan. Dynamic mid-sagittal posterior tongue and mandible movements during passive jaw advancement were measured with tagged MRI. Upper airway cross-sectional areas were measured with the mandible in a neutral position and advanced to 70% of maximum advancement. Treatment outcome was determined after a minimum of 9 weeks of therapy. Results: Seventy-one participants completed the study: 33 were responders (AHI50% AHI reduction), 11 were partial responders (>50% AHI reduction but AHI>10 events/hr), and 27 nonresponders (AHI reduction 4 mm). In comparison, a model using only baseline AHI correctly classified 50.0% of patients (5-fold cross-validated 52.5%, n = 40). Conclusions: Tongue advancement and upper airway enlargement with mandibular advancement in conjunction with baseline AHI improve treatment response categorization to a satisfactory level (69.2%, 5-fold cross-validated 62.5%)

Regional temperature control in ceramic injection moulding: an approach based on cooling rate optimisation

The injection moulding of ceramic components with uneven wall thickness presents challenges due to differential cooling rates developing in the injected parts, which cause premature solidification of the feedstock at thin features and lead to detrimental defects , worsening in components from green to sintered states. To cope with this, suitable mould thermal control approaches have to be selected and validated, as current control methods are based on the achievement of a uniform cavity surface temperature, which is not tailored to such complex geometries. In this work, a novel thermal control system is proposed, based on regional mould temperatures, implemented with the use of Peltier modules, which locally and independently heat and cool different cavity features according to their thickness. The regional temperature profiles are optimised over time with the use of a coupled Finite Element-Particle Swarm Optimisation (FE-PSO), to achieve uniform cooling rates throughout the moulded components. The performance of this approach is compared to both constant ambient mould temperature and Rapid Heat Cycle Moulding (RHCM) techniques, which instead aim at achieving uniform temperatures throughout the mould cavity surface. Results show that the novel proposed method, based on regional temperature control and uniform cooling rates, promotes the simultaneous solidification of features with a 10-times difference in surface-to-volume ratio. Due to this, in terms of components quality, the novel method brings the advantages 1 of higher dimensional control and reduction of differential shrinkage compared to the other analysed approaches, thus increasing the capability to use injection moulding to manufacture ceramic components characterised by non-uniform wall thickness

Manufacturing at double the speed

The speed of manufacturing processes today depends on a trade-off between the physical processes of production, the wider system that allows these processes to operate and the co-ordination of a supply chain in the pursuit of meeting customer needs. Could the speed of this activity be doubled? This paper explores this hypothetical question, starting with examination of a diverse set of case studies spanning the activities of manufacturing. This reveals that the constraints on increasing manufacturing speed have some common themes, and several of these are examined in more detail, to identify absolute limits to performance. The physical processes of production are constrained by factors such as machine stiffness, actuator acceleration, heat transfer and the delivery of fluids, and for each of these, a simplified model is used to analyse the gap between current and limiting performance. The wider systems of production require the co-ordination of resources and push at the limits of human biophysical and cognitive limits. Evidence about these is explored and related to current practice. Out of this discussion, five promising innovations are explored to show examples of how manufacturing speed is increasing ? with line arrays of point actuators, parallel tools, tailored application of precision, hybridisation and task taxonomies. The paper addresses a broad question which could be pursued by a wider community and in greater depth, but even this first examination suggests the possibility of unanticipated innovations in current manufacturing practices

Polymerase delta-interacting protein 38 (PDIP38) modulates the stability and activity of the mitochondrial AAA+ protease CLPXP

Over a decade ago Polymerase δ interacting protein of 38 kDa (PDIP38) was proposed to play a role in DNA repair. Since this time, both the physiological function and subcellular location of PDIP38 has remained ambiguous and our present understanding of PDIP38 function has been hampered by a lack of detailed biochemical and structural studies. Here we show, that human PDIP38 is directed to the mitochondrion in a membrane potential dependent manner, where it resides in the matrix compartment, together with its partner protein CLPX. Our structural analysis revealed that PDIP38 is composed of two conserved domains separated by an α/β linker region. The N-terminal (YccV-like) domain of PDIP38 forms an SH3-like β-barrel, which interacts specifically with CLPX, via the adaptor docking loop within the N-terminal Zinc binding domain of CLPX. In contrast, the C-terminal (DUF525) domain forms an immunoglobin-like β-sandwich fold, which contains a highly conserved putative substrate binding pocket. Importantly, PDIP38 modulates the substrate specificity of CLPX and protects CLPX from LONM-mediated degradation, which stabilises the cellular levels of CLPX. Collectively, our findings shed new light on the mechanism and function of mitochondrial PDIP38, demonstrating that PDIP38 is a bona fide adaptor protein for the mitochondrial protease, CLPXP

At the coalface and the cutting edge: general practitioners’ accounts of the rewards of engaging with HIV medicine

The interviews we conducted with GPs suggest that an engagement with HIV medicine enables clinicians to develop strong and long-term relationships with and expertise about the care needs of people living with HIV ‘at the coalface’, while also feeling connected with a broader network of medical practitioners and other professionals concerned with and contributing to the ever-changing world of science: ‘the cutting edge’. The general practice HIV prescriber is being modelled here as the interface between these two worlds, offering a rewarding opportunity for general practitioners to feel intimately connected to both community needs and scientific change