Yeti crab - optimal warehouse layout

The purpose of Project Yeti Crab was to develop and provide recommendations as to how Synlait Milk Limited can improve the performance of warehouse operations by optimising its layout. This business case presents the recommended approach for Synlait to optimise its warehouse layout in the near future, and the associated costs and benefits of doing so. Details as to the basis of these recommendations, as well as the process by which they were developed are included in the supporting documents

In vitro caries: dental plaque formation and acidogenicity

Dental caries is a significant disease world-wide and although a massive reduction in prevalence has occurred over the past 50 years, incidents of this disease persist (particularly on the occlusal or aproximal surfaces and concerning younger demographics). The main reason for the observed reduction is exposure to fluoride either though water fluoridation and delivery by dentifrice. Environmental exposure reduces incidence by incorporation into the mineral phase of the hard tissue and, as a result, increases the resistance of the enamel mineral to acid-induced demineralisation. Several mechanisms have been proposed in an attempt to explain the caries-inhibiting effects of fluoride however its influence on the balance between de- and re-mineralisation episodes appears to be the principal route by which fluorides exert their effects. Efforts geared towards the continual improvement of fluoride delivery systems have also been successful to some extent and thus further exploration shows promise of improving the anticaries efficacy further. However, a complication is met in that, in vivo, multiple factors interrelated and consequently, differences in the consortia within natural oral biofilms combined with unavoidable inter-individual variations confound clinical investigations and make the distinction between relevant aspects of the process difficult. One possible alternative strategy is the development of in vitro biological models to simulate this process to a point of reflecting the in vivo situation whilst retaining control over the parameters which are known to be crucial to the progression of the disease. To this end, the Constant-Depth Film Fermenter (CDFF) has emerged as powerful tool to potentially meet the needs of current in vitro research. However, due to the lack of an inter-disciplinary approach to multi-faceted disease process, the full potential of the CDFF has not yet been reached. Therefore, the CDFF model was applied to study of anti-caries strategies which aimed to increase the persistence of the fluorides within natural microcosm biofilms. Enamel lesions were successfully produced within this system and, using a combination of both biological and non-biological demineralisations systems, the effects of anticaries agents (calcium and fluoride) were also investigated for their effects on lesion progression or reversal. Sodium fluoride (NaF; 300 ppm F-) exposures exhibited an ambiguous response on the microbial community although definite anticaries activity. Conversely, calcium lactate pre-rinses (Ca-lactate; 100 mM) appears to possess some inhibitory activity on the biofilms produced within the model whereas a less effective anticaries activity was observed in comparison to NaF exposures alone. Thus, further investigation of the effects of Ca-lactate should be pursued. Operation of the CDFF was also further developed to meet the needs of this study and analyses were performed on an integrative basis in order to capture the physiochemical events which take place during caries lesion formation. Microcosm plaques were shown to be highly diverse with respect to their community although homology was found on the bias of their ultimate definition, cariogenicity. The synthesis of inorganic mineral reservoirs within microcosm biofilms holds great potential for augmenting the physiology of the plaque and for increasing the efficacy of fluorides for prevention of enamel demineralisation. Microcosm biofilms may also have an adaptive capacity which could result in predicable response patterns. Ultimately, a holistic approach to the study of caries within a biological context provides greater insight into the caries process than approaches which lack specific interactions for the purposes of assigning direct relationships. With the successful development of a fully functional enamel caries model, the possibilities are endless

The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM

AimsThe two predominant pathophysiological defects resulting in glucose intolerance are beta-cell dysfunction and insulin insensitivity. This study aimed to re-examine beta-cell function and insulin sensitivity across a continuum from normal glucose tolerance (NGT) to early type 2 diabetes (T2DM) employing highly specific insulin, C-peptide and intact proinsulin assays.Materials and methodsA total of 104 persons with NGT, 85 with impaired glucose tolerance (IGT) and 554 with newly diagnosed T2DM were investigated. Following an overnight fast, all underwent a 4-h standardised mixed meal tolerance test (MTT), and on a second day, a sub-group underwent a frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT) over a 3-h period. The participants were stratified according to fasting glucose and BMI for analysis.ResultsThe MTT revealed that increasing FPG was accompanied by progressively elevated and delayed postprandial glucose peaks. In parallel, following an initial compensatory increase in fasting and postprandial insulin responses there followed a progressive demise in overall beta-cell secretory capacity. FSIVGTT demonstrated a major reduction in the early insulin response to IV glucose in persons with IGT accompanied by a dramatic fall in insulin sensitivity. Beyond pre-diabetes, ever-increasing fasting and postprandial hyperglycaemia resulted predominantly from a progressively decreasing beta-cell secretory function.ConclusionThis study utilising improved assay technology re-affirms that beta-cell dysfunction is evident throughout the spectrum of glucose intolerance, whereas the predominant fall in insulin sensitivity occurs early in its evolution

Improved Rheometry of Yield Stress Fluids Using Bespoke Fractal 3D Printed Vanes

To enable robust rheological measurements of the properties of yield stress fluids, we introduce a class of modified vane fixtures with fractal-like cross-sectional structures. A greater number of outer contact edges leads to increased kinematic homogeneity at the point of yielding and beyond. The vanes are 3D printed using a desktop stereolithography machine, making them inexpensive (disposable), chemically-compatible with a wide range of solvents, and readily adaptable as a base for further design innovations. To complete the tooling set, we introduce a textured 3D printed cup, which attaches to a standard rheometer base. We discuss general design criteria for 3D printed rheometer vanes, including consideration of sample volume displaced by the vanes, stress homogeneity, and secondary flows that constrain the parameter space of potential designs. We also develop a conversion from machine torque to material shear stress for vanes with an arbitrary number of arms. We compare a family of vane designs by measuring the viscosity of Newtonian calibration oils with error <5% relative to reference measurements made with a cone-and-plate geometry. We measure the flow curve of a simple Carbopol yield stress fluid, and show that a 24-arm 3D printed fractal vane agrees within 1% of reference measurements made with a roughened cone-and-plate geometry. Last, we demonstrate use of the 24-arm fractal vane to probe the thixo-elasto-visco-plastic (TEVP) response of a Carbopol-based hair gel, a jammed emulsion (mayonnaise), and a strongly alkaline carbon black-based battery slurry

Development and characterization of an in vitro system of the human retina using cultured cell lines

Background: Previously developed in vitro cultures of the human retina have been solo or dual cell cultures. We developed a triple-cell culture in vitro model utilizing a membrane system to produce a better representation of a functional and morphological human retina. Methods: Retinal microvascular endothelial cells (HRMVEC/ACBRI181, Cell systems), retinal pigment epithelium cells (RPE/ARPE-19, ATCC) and Müller glial cells (MIO-M1, UCL) were grown in a triple-culture. Our optimized triple-culture media contained a mix of specific endothelial medium and high glucose Dulbecco's Modified Eagle's medium (DMEM), where all three layers were viable for up to 5 days. Co-culture effect on morphological changes (cell staining) and gene expression of functional genes (pigment epithelial derived factor (PEDF) and vascular endothelial growth factor (VEGF)) were measured from RNA via real time PCR. Expression of tight junction protein 1 (TJP1) was measured in RNA isolated from ARPE-19s, to assess barrier stability. Results: The triple-culture promotes certain cell functionality through up-regulation of TJP1, increasing PEDF and decreasing VEGF expression highlighting its importance for the assessment of disease mechanisms distinct from a solo culture which would not allow the true effect of the native microenvironment to be elucidated. Conclusion: This model's novelty and reliability allows for the assessment of singular cellular function within the retinal microenvironment and overall assessment of retinal health, whilst eliminating the requirement of animal-based models

Frost fairs, sunspots and the Little Ice Age

Mike Lockwood, Mat Owens, Ed Hawkins, Gareth S. Jones and Ilya Usoskin examine the links between the solar Maunder minimum, the Little Ice Age and the freezing of the River Thame

Recognising and responding to suicidal crisis within family and social networks: qualitative study

Objective To shed light on the difficulties faced by relatives, friends, and colleagues in interpreting signs of suicidality and deciding whether and how to intervene

How people come to recognise a problem and seek medical help for a person showing early signs of dementia: a systematic review and meta-ethnography

Evidence suggests that there is usually a long delay between noticing first signs of dementia and seeking medical help. We conducted a systematic review of what people experience and how they make decisions during this time, and used a meta-ethnographic approach to synthesise the findings. Screening and quality assessment resulted in nine studies eligible for inclusion. People with dementia mainly report experiencing memory lapses, while carers focus on more subtle changes in personality. People respond to these changes in one of three ways: 1) they discount them as normal; 2) they reserve judgement as to their cause and significance, or 3) they misattribute them. Pivotal events can finally trigger help seeking. Active reflection and seeking of further evidence may lead to earlier recognition of the possibility of dementia and the need to seek help; it also reduces the risk of a pivotal event. Public education should aim to improve recognition of more subtle signs and to encourage repeated evaluation and reflection

How Dilute are Dilute Solutions in Extensional Flows?

Submitted to J. Rheol.We investigate the concentration-dependence of the characteristic relaxation time of dilute polymer solutions in transient uniaxial elongational flow. A series of monodisperse polystyrene solutions of five different molecular weights (1.8×10^6 ≤ M ≤ 8.3×10^6 g/mol) with concentrations spanning five orders of magnitude were dissolved in two solvents of differing solvent quality (diethyl phthalate and oligomeric styrene). Optical measurements of the rate of filament thinning and the time to break-up in each fluid are used to determine the characteristic relaxation time. A lower sensitivity limit for the measurements was determined experimentally and confirmed by comparison to numerical calculations. Above this sensitivity limit we show that the effective relaxation time of moderately dilute solutions (0.01 ≤ c/c* ≤ 1) in transient extensional flow rises substantially above the fitted value of the relaxation time extracted from small amplitude oscillatory shear flow and above the Zimm relaxation time computed from kinetic theory and intrinsic viscosity measurements. This effective relaxation time exhibits a power-law scaling with the reduced concentration (c/c*) and the magnitude of the exponent varies with the thermodynamic quality of the solvent. This scaling appears to be roughly consistent to that predicted when the dynamics of the partially elongated and overlapping polymer chains are described within the framework of blob theories for semi-dilute solutions.NASA Microgravity Fluid Dynamic