A dissertation and review of current knowledge on aspects relating to the use of Remifentanil to cover the tunnelling phase of Ventriculoperitoneal Shunt Insertion in paediatrics

In this study, the administration of remifentanil to cover the tunnelling phase of shunt insertion in children caused good attenuation of haemodynamic and endocrine markers of stress, no delay in recovery and no additional post operative respiratory depression in all age groups, including xpremies and neonates

Visual crowding is unaffected by adaptation-induced spatial compression

It has recently been shown that adapting to a densely textured stimulus alters the perception of visual space, such that the distance between two points subsequently presented in the adapted region appears reduced (Hisakata, Nishida, & Johnston, 2016). We asked whether this form of adaptation-induced spatial compression alters visual crowding. To address this question, we first adapted observers to a dynamic dot texture presented within an annular region surrounding the test location. Following adaptation, observers perceived a test array comprised of multiple oriented dot dipoles as spatially compressed, resulting in an overall reduction in perceived size. We then tested to what extent this spatial compression influences crowding by measuring orientation discrimination of a single dipole flanked by randomly oriented dipoles across a range of separations. Following adaptation, we found that the magnitude of crowding was predicted by the physical-rather than perceptual-separation between centre and flanking dipoles. These findings contrast with previous studies in which crowding has been shown to increase when motion-induced position shifts act to reduce apparent separation (Dakin, Greenwood, Carlson, & Bex, 2011; Maus, Fischer, & Whitney, 2011)

Inactivation of mammalian Ero 1α is catalysed by specific protein disulfide isomerases

Disulfide formation within the endoplasmic reticulum is a complex process requiring a disulfide exchange protein such as protein disulfide isomerase and a mechanism to form disulfides de novo. In mammalian cells, the major pathway for de novo disulfide formation involves the enzyme Ero1α which couples oxidation of thiols to the reduction of molecular oxygen to form hydrogen peroxide. Ero1α activity is tightly regulated by a mechanism that requires the formation of regulatory disulfides. These regulatory disulfides are reduced to activate and reform to inactive the enzyme. To investigate the mechanism of inactivation we analysed regulatory disulfide formation in the presence of various oxidants under controlled oxygen concentration. Neither molecular oxygen, nor hydrogen peroxide was able to oxidise Ero1α efficiently to form the correct regulatory disulfides. However, specific members of the PDI family such as PDI or ERp46 were able to catalyse this process. Further studies showed that both active sites of PDI contribute to the formation of regulatory disulfides in Ero1α and that the PDI substrate binding domain is crucial to allow electron transfer between the two enzymes. These results demonstrate a simple feedback mechanism of regulation of mammalian Ero1α involving its primary substrate

Development of a low cost acoustic emission early warning system for slope instability

Slope failures world-wide cause many thousands of deaths each year and damage built environment infrastructure. There is a clear need for low cost instrumentation that can provide an early warning of slope instability to enable evacuation of vulnerable people and timely repair and maintenance of critical infrastructure. Current instrumentation systems are either too expensive for wide scale use or have technical limitations. An approach, Assessment of Landslides using Acoustic Real-time Monitoring Systems (ALARMS), has been developed and demonstrated through research. An approach has been developed using measurement of acoustic emission generated during the onset of slope failure to provide quantitative information on slope displacement rates. Research is in progress to develop low cost acoustic sensors. A unitary acoustic emission slope displacement rate sensor has been designed and is being trialled in an active landslide. Continuous monitored acoustic emission rates show comparable trends to displacement rates measured using an inclinometer. Acoustic emission increase after rainfall events and this is considered to indicate increased displacement rates

A PC parallel port button box provides millisecond response time accuracy under Linux

For psychologists, it is sometimes necessary to measure people's reaction times to the nearest millisecond. This article describes how to use the PC parallel port to receive signals from a button box to achieve millisecond response time accuracy. The workings of the parallel port, the corresponding port addresses, and a simple Linux program for controlling the port are described. A test of the speed and reliability of button box signal detection is reported. If the reader is moderately familiar with Linux, this article should provide sufficient instruction for him or her to build and test his or her own parallel port button box. This article also describes how the parallel port could be used to control an external apparatus

Reconstruction of landslide movements by inversion of 4D electrical resistivity tomography monitoring data

Reliable tomographic inversion of geoelectrical monitoring data from unstable slopes relies critically on knowing the electrode positions, which may move over time. We develop and present an innovative inverse method to recover movements in both surface directions from geoelectrical measurements made on a grid of monitoring electrodes. For the first time, we demonstrate this method using field data from an active landslide to recover sequences of movement over timescales of days to years. Comparison with GPS measurements demonstrated an accuracy of within 10 % of the electrode spacing, sufficient to correct the majority of artefacts that would occur in subsequent image reconstructions if incorrect positions are used. Over short timescales where the corresponding subsurface resistivity changes were smaller, the constraints could be relaxed and an order-of-magnitude better accuracy was achievable. This enabled the onset and acceleration of landslide activity to be detected with a temporal resolution of a few days

Assessment of ground-based monitoring techniques applied to landslide investigations

A landslide complex in the Whitby Mudstone Formation at Hollin Hill, North Yorkshire, UK is periodically re-activated in response to rainfall-induced pore-water pressure fluctuations. This paper compares long-term measurements (i.e., 2009 – 2014) obtained from a combination of monitoring techniques that have been employed together for the first time on an active landslide. The results highlight the relative performance of the different techniques, and can provide guidance for researchers and practitioners for selecting and installing appropriate monitoring techniques to assess unstable slopes. Particular attention is given to the spatial and temporal resolution offered by the different approaches that include: Real Time Kinematic-GPS (RTK-GPS) monitoring of a ground surface marker array, conventional inclinometers, Shape Acceleration Arrays (SAA), tilt meters, active waveguides with Acoustic Emission (AE) monitoring, and piezometers. High spatial resolution information has allowed locating areas of stability and instability across a large slope. This has enabled identification of areas where further monitoring efforts should be focused. High temporal resolution information allowed the capture of S’-shaped slope displacement-time behaviour (i.e. phases of slope acceleration, deceleration and stability) in response to elevations in pore-water pressures. This study shows that a well-balanced suite of monitoring techniques that provides high temporal and spatial resolution on both measurement and slope scale is necessary to fully understand failure and movement mechanisms of slopes. In the case of the Hollin Hill landslide it enabled detailed interpretation of the geomorphological processes governing landslide activity. It highlights the benefit of regularly surveying a network of GPS markers to determine areas for installation of movement monitoring techniques that offer higher resolution both temporally and spatially. The small sensitivity of tilt meter measurements to translational movements limited the ability to record characteristic ‘S’-shaped landslide movements at Hollin Hill, which were identified using SAA and AE measurements. This high sensitivity to landslide movements indicates the applicability of SAA and AE monitoring to be used in early warning systems, through detecting and quantifying accelerations of slope movement

Efficacy and safety of oral methazolamide in patients with type 2 diabetes: A 24-week, placebo-controlled, double-blind study

OBJECTIVE To evaluate the safety and efficacy of methazolamide as a potential therapy for type 2 diabetes. RESEARCH DESIGN AND METHODS This double-blind, placebo-controlled study randomized 76 patients to oral methazolamide (40 mg b.i.d.) or placebo for 24 weeks. The primary efficacy end point for methazolamide treatment was a placebo-corrected reduction in HbA1c from baseline after 24 weeks (ΔHbA1c). RESULTS Mean ± SD baseline HbA1c was 7.1 ± 0.7% (54 ± 5 mmol/mol; n = 37) and 7.4 ± 0.6% (57 ± 5 mmol/mol; n = 39) in the methazolamide and placebo groups, respectively. Methazolamide treatment was associated with a ΔHbA1c of –0.39% (95% CI –0.82, 0.04; P < 0.05) (–4.3 mmol/mol [–9.0, 0.4]), an increase in the proportion of patients achieving HbA1c ≤6.5% (48 mmol/mol) from 8 to 33%, a rapid reduction in alanine aminotransferase (∼10 units/L), and weight loss (2%) in metformin-cotreated patients. CONCLUSIONS Methazolamide is the archetype for a new intervention in type 2 diabetes with clinical benefits beyond glucose control

Recruitment of inflammatory monocytes by senescent fibroblasts inhibits antigen-specific tissue immunity during human aging

We have previously shown that healthy older adults exhibit reduced cutaneous immune responses during a varicella zoster virus (VZV) antigen challenge that correlated with a nonspecific inflammatory response to the injection itself. Here we found that needle damage during intradermal injections in older adults led to an increase in the number of cutaneous senescent fibroblasts expressing CCL2, resulting in the local recruitment of inflammatory monocytes. These infiltrating monocytes secreted prostaglandin E2, which inhibited resident memory T cell activation and proliferation. Pretreatment of older participants with a p38 mitogen-activated protein kinase inhibitor in vivo decreased CCL2 expression and inhibited monocyte recruitment and secretion of prostaglandin E2. This coincided with an increased response to VZV antigen challenge in the skin. Our results point to a series of molecular and cellular mechanisms that link cellular senescence, tissue damage, excessive inflammation and reduced immune responsiveness in human skin and demonstrate that tissue-specific immunity can be restored in older adults by short-term inhibition of inflammatory responses